ThereAreNoSunglasses

American Resistance To Empire

CDC Admits That Up To 4,100 Have Died After Covid Vax, Mainstream Media Still Promoting Lie of “No Deaths”

[AP analysis: Almost all US coronavirus deaths among unvaccinated]

  • 4,115 people have been hospitalized or died with Covid-19 despite being fully vaccinated.
  • The total number of individuals who died after contracting Covid-19 despite vaccination is 750.
  • 76% of hospitalizations and deaths from breakthrough cases occurred in people over the age of 65.
U.S. Air Force 1st Lt. Allyson Black (R), a registered nurse, cares for COVID-19 patients in a makeshift ICU (Intensive Care Unit) at Harbor-UCLA Medical Center on January 21, 2021 in Torrance, California.
U.S. Air Force 1st Lt. Allyson Black (R), a registered nurse, cares for COVID-19 patients in a makeshift ICU (Intensive Care Unit) at Harbor-UCLA Medical Center on January 21, 2021 in Torrance, California.
Mario Tama | Getty Images

More than 4,100 people have been hospitalized or died with Covid-19 in the U.S. even though they’ve been fully vaccinated, according to new data from the Centers for Disease Control and Prevention.

So far, at least 750 fully vaccinated people have died after contracting Covid, but the CDC noted that 142 of those fatalities were asymptomatic or unrelated to Covid-19, according to data as of Monday that was released Friday.

The CDC received 3,907 reports of people who have been hospitalized with breakthrough Covid infections, despite being fully vaccinated. Of those, more than 1,000 of those patients were asymptomatic or their hospitalizations weren’t related to Covid-19, the CDC said.

Former FDA commissioner Dr. Scott Gottlieb on delta variant concerns

“To be expected,” Dr. Paul Offit, a top advisor to the Food and Drug Administration on children’s vaccines told CNBC. “The vaccines aren’t 100% effective, even against severe disease. Very small percentage of the 600,000 deaths.”

Breakthrough cases are Covid-19 infections that bypass vaccine protection. They are very rare and many are asymptomatic. The vaccines are highly effective but don’t block every infection. Pfizer and Moderna’s phase three clinical studies found that their two-dose regimens were 95% and 94% effective at blocking Covid-19, respectively, while Johnson & Johnson’s one-shot vaccine was found to be 66% effective in its studies. All three, however, have been found to be extremely effective in preventing people from getting severely sick from Covid.

The CDC doesn’t count every breakthrough case. It stopped counting all breakthrough cases May 1 and now only tallies those that lead to hospitalization or death, a move the agency was criticized for by health experts.

Most Americans have received at least one shot of the two currently authorized mRNA vaccines. The U.S. has administered 178.3 million shots and fully vaccinated 46% of its population.

“You are just as likely to be killed by a meteorite as die from Covid after a vaccine,” Dr. Peter Chin-Hong, an infectious disease expert at the University of California San Francisco, told CNBC. “In the big scheme of things, the vaccines are tremendously powerful.”

Efficacy rates decrease slightly for variants like alpha and delta, with studies indicating 88% efficacy against the delta strain after two doses of the Pfizer vaccine. It was unclear if any of the reported breakthrough cases were caused by variants.

In Israel and the United Kingdom, concerns about the delta variant are rising after growing reports of breakthrough infections.

Even with 80% of adults vaccinated, Chezy Levy, director-general of Israel’s Health Ministry, said the delta variant is responsible for 70% of new infections in the country. Levy also said that one-third of those new infections were in vaccinated individuals.

In the U.K., Public Health England released a report that found 26 out of 73 deaths caused by the delta variant occurred in fully vaccinated people from June 8 to June 14. Most of the deaths occurred in unvaccinated individuals.

“Determination of whether hospitalizations and deaths are more represented in immunocompromised patients and the type of vaccine received will be important for future guidance,” Chin-Hong said.

UCLA Epidemiology Professor Dr. Anne Rimoin on delta Covid variant

On June 7, the CDC received reports of 3,459 breakthrough cases that led to hospitalization or death. On June 18, that number was updated to 3,729, an increase of 270 cases. Today, the number stands at 4,115.

An overwhelming majority, 76%, of the hospitalizations and deaths from breakthrough cases occurred in people over the age of 65.

We do not have the years and years of data we have for vaccines against other airborne pathogens — and therefore it is really essential that the CDC provides up to date reporting on breakthrough cases,” David Edwards, aerosol scientist and Harvard University professor, told CNBC.

The CDC says its numbers are “likely an undercount” of all Covid infections in vaccinated people because the data relies on passive and voluntary reporting.

— CNBC’s Berkeley Lovelace Jr. contributed to this report.

Biden Rejects Basis of 2nd Amendment and Declaration of Independence

[The Declaration of Independence]

Biden touts new crime prevention strategy focused on gun control

He rejected the argument that the right to self-defense is needed to protect against potential government tyranny

Biden met with state and local leaders and law enforcement officials ahead of his remarks to talk crime prevention strategy, amid a surge in violence in cities across the U.S.

Both Biden and Attorney General Merrick Garland, who spoke before him, pointed to a historic rise in crime in the summertime, and said that rise “may be more pronounced” as the nation comes out of the COVID-19 pandemic.

The White House has insisted curbing gun violence is key to tamping down a “staggering” surge of crime across the U.S.

“Talk to most responsible gun owners they’ll tell you there’s no possible justification for having 100 rounds in a magazine,” Biden said.

Biden also took aim at an argument used by Second Amendment advocates, that the right to self-defense needed to protect against potential government tyranny.

“Those who say the blood of Patriots, you know, and all the stuff about how we’re gonna have to move against the government,” Biden said. “If you think you need to have weapons to take on the government, you need F-15s and maybe some nuclear weapons.”

“We’re not changing the Constitution. We’re enforcing it,” the president continued.
Biden touted “zero tolerance” for gun dealers who willfully violate the law, and claimed that 90% of illegal guns found at crime scenes were traced back to 5% of gun dealers.

The “zero-tolerance” policy targets federally licensed firearms dealers who “willfully” transfer a weapon to someone prohibited from owning one or ignore a tracing request from the Bureau of Alcohol, Tobacco, Firearms and Explosives (ATF). The ATF would seek to revoke the dealer’s license after the first offense, a senior White House official said.

“If you willfully sell a gun to someone who’s prohibited from possessing it, if you willfully fail to run a background check, if you willfully falsify a record … my message to you is this: We’ll find you and we will seek your license to sell guns,” Biden said.

The National Rifle Association said the Biden initiative was an attempt to distract from the true causes of a rise in crime.

“This is a political red herring aimed at hiding the real and abysmal failures of the Biden administration,” NRS spokeswoman Amy Hunter told Fox News. “Crime rates are high because of the efforts to defund the police and a failure to prosecute career criminals. The simple fact is strict enforcement of existing laws – including gun laws – coupled with support of law enforcement and prosecutors to do their jobs would result in a dramatic decrease in crime. But, the president would rather play politics than make Americans safer.”

Biden also boasted of “historic funding for crime prevention” in the $350 billion for state and local governments, from the $1.9 trillion COVID-19 relief package, that can be used by cities to hire law enforcement officers, pay overtime, prosecute gun traffickers and invest in technology to make law enforcement more efficient. Officials said the Biden administration hoped cities would choose to use the money for alternatives to policing, too, and to invest in community policing models.

The administration has also taken aim at “ghost guns” and modified firearms, which are homemade firearms without serial numbers that can be used to trace them, making it difficult for law enforcement to determine where, by whom, or when they were manufactured and to whom they were sold.

The Justice Department’s ATF last month sought to update the legal definition of “firearm” in an effort to crack down on ghost guns.

Biden also pushed hiring programs to keep young people busy and off the streets during the summer months, as they’re often both the target and perpetrators of such violence. Biden said such programs encouraged youth to “pick up a paycheck instead of a pistol.”

The president said the DOJ has created five new “strike forces” to crack down on illegal gun trafficking cartels and called on the Senate to reauthorize the Violence Against Women Act, thereby closing the “boyfriend loophole” to keep guns out of the hands of domestic abusers.

The Biden/Democrat Hunt For “Domestic Terrorists” and the Coming “Internet Purge”

[The White House on Tuesday released a report that designates the Jan. 6 Capitol riot a “domestic terrorist attack” and endorses an internet purge of “extremist” content–NY POST]

 “National Strategy for Countering Domestic Terrorism.”–pdf

Domestic terrorism – driven by hate, bigotry, and other forms of extremism— is a stain on the soul of America.  It goes against everything our country strives for and it poses a direct challenge to our national security, democracy, and unity.

To meet this serious and growing threat, on my first day in office I directed my national security team to confront the rise in domestic terrorism with the necessary resources and resolve.  Today, I am releasing the first-ever National Strategy for Countering Domestic Terrorism.  It lays out a comprehensive approach to protecting our nation from domestic terrorism while safeguarding our bedrock civil rights and civil liberties – values that make us who we are as Americans.  We have to take both short-term steps to counter the very real threats of today and longer-term measures to diminish the drivers that will contribute to this ongoing challenge to our democracy.

This is a project that should unite all Americans.  Together we must affirm that domestic terrorism has no place in our society.  We must work to root out the hatreds that can too often drive violence.  And we must recommit to defending and protecting our basic freedoms, which belong to all Americans in equal measure, and which are not only the foundation of our democracy – they are our enduring advantage in the world.

Is “Magnetic Drug Delivery” The Source of Magnetic Shot Conspiracy Theory?

Hot New Conspiracy Theory: Vaccines Turn You Into a Magnet

Magnetic Drug Delivery: Where the Field Is Going

Paige M. Price1Waleed E. Mahmoud2Ahmed A. Al-Ghamdi2 and Lyudmila M. Bronstein1,2,3*
  • 1Department of Chemistry, Indiana University, Bloomington, IN, United States
  • 2Department of Physics, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
  • 3A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Moscow, Russia

Targeted delivery of anticancer drugs is considered to be one of the pillars of cancer treatment as it could allow for a better treatment efficiency and less adverse effects. A promising drug delivery approach is magnetic drug targeting which can be realized if a drug delivery vehicle possesses a strong magnetic moment. Here, we discuss different types of magnetic nanomaterials which can be used as magnetic drug delivery vehicles, approaches to magnetic targeted delivery as well as promising strategies for the enhancement of the imaging-guided delivery and the therapeutic action.

Introduction

The majority of anticancer drugs are delivered intravenously and accumulated in tumors containing the abundance of leaking blood vessels. However, this affects healthy tissue and causes numerous side effects. The more efficient approach is realized when drug nanocarriers are functionalized with target molecules [for example, folate (FA) groups], which interact with specific receptors located in certain tumors, allowing for the attachment of the drug delivery vehicles solely to the tumor (Fernandez et al., 2018Rosiere et al., 2018Sun, Q. et al., 2018Sun, W. et al., 2018). This approach allows for a significant decrease of side effects caused by chemotherapy agents (Li et al., 2017Peng et al., 2017Sun, W. et al., 2018). Another drug delivery approach which can be used for many types of tumors is magnetic drug targeting which can be achieved if a drug delivery vehicle possesses a strong magnetic moment and can be manipulated by a magnetic field (Lee et al., 2017Luong et al., 2017Wei et al., 2017).

Magnetic drug delivery was first introduced in the 80’s (Widder et al., 1980Kost and Langer, 1986) but in the last decade the interest to magnetic targeting soared due to the development of stronger magnets and higher sophistication magnetic probes with multiple functions, i.e., theranostic probes (Nan et al., 2017Sun, Q. et al., 2018Tang et al., 2018). Such probes allow for a combination of diagnostics (magnetic resonance imaging (MRI) or magnetic particle imaging), and therapeutics, which could include hyperthermia and drug release as well as targeted drug delivery (for example, with an applied magnetic field).

A substantial number of reviews has been published on magnetic drug delivery (Kost and Langer, 1986Lubbe et al., 2001Duran et al., 2008Herrmann et al., 2009Williams et al., 2009Foy and Labhasetwar, 2011Tietze et al., 20122015Mody et al., 2014Lyer et al., 2015Mitra et al., 2015Shapiro et al., 2015), the latest of which appeared as recently as 2016–2017 (Ulbrich et al., 2016Grillone and Ciofani, 2017Kralj et al., 2017Mosayebi et al., 2017). However, the explosive development of this field in the last two years reveals the need in reviewing recent findings and better understanding of the major trends and shortcomings.

Development of Magnetic Drug Delivery Probes

Currently, there are many different types of magnetic bioprobes which are being explored for magnetic targeting. In this review, we will focus on the most promising bioprobes from the viewpoint of magnetic manipulation and loading/release of specific drugs.

Magnetic Nano/Microparticles

Magnetic microspheres were developed to overcome two major issues that are present with non-magnetic microcarriers: reticuloendothelial system clearance and poor site specificity (Kakar et al., 2013). One of the approaches is to develop porous or hollow/porous microspheres from magnetic spinel ferrites MxFe3−xO4 (M = Fe, Zn). Their high magnetism means the microspheres can be easily manipulated by a magnet within the vascular system and, more specifically, remain in the target organ capillaries. Chen et al. utilized a hollow nanoparticle (NP) with a mesoporous shell which creates a higher surface area and a large cavity where drug can be encapsulated in both the mesopores and the cavities (Chen et al., 2017). Additionally, MxFe3−xO4 (M = Fe, Zn) produce more heat under microwave irradiation which allows easier release of the loaded drug. However, doping of iron oxide causes the decrease of the saturation magnetization which diminishes the microsphere potential for magnetic targeting (Chen et al., 2017).

Another approach to synthesizing microspheres is the combination of a polymer with inorganic NPs. Wang et al. utilized poly(ε-caprolactone) (PCL) to encapsulate both Fe3O4 NPs and the anti-cancer drug, doxorubicin hydrochloride (DOX) (Wang, G. et al., 2018). The superparamagnetic composite microspheres showed a high drug loading and a quick magnetic response. The drug release was shown to be pH-sensitive with a high initial release and sustained release over many days.

Microparticles of dry powder chemotherapeutic containing iron oxide NPs (called nano-in-microparticles, NIMs) were used for magnetic delivery into lungs with an applied magnetic field (Price et al., 2017). Mice were endotracheally administered fluorescently labeled NIMs as a dry powder in the presence of an external magnet placed over one lung. It was demonstrated that in the magnetically activated lung, DOX loaded NIMs were therapeutically efficient, thus allowing for a targeted delivery.

Specific gene delivery has been realized with biomimetic magnetic microparticles (magnetosomes) synthesized utilizing magnetic nanocluster (MNC) core and Arg–Gly–Asp (RGD) decorated macrophage shell (Zhang et al., 2018). The magnetosome synthesis was accomplished via several steps including MNC preparation, azide-membrane engineering, electrostatic assembly, and click chemistry. This complex approach to magnetosomes is well-justified, allowing for high-performance siRNA delivery through a superior stealth effect, MRI, magnetic accumulation via an external magnetic field, RGD targeting, and favorable cytoplasm trafficking.

Drug-loaded microparticles prepared by layer-by-layer (LbL) deposition of polyelectrolytes with embedded magnetic NPs were attached to Escherichia coli bacteria, creating stochastic “microswimmers” which moved at average speeds of up to 22.5 μm/s (Park et al., 2017). These “microswimmers” displayed biased and directional motion under a chemoattractant gradient and a magnetic field, respectively. This work demonstrates that multifunctional bacteria-driven magnetic bioprobes can be used for targeted drug delivery with significantly enhanced drug transfer in comparison to passive microparticles. Another interesting example of “microswimmers” was reported in (Stanton et al., 2017). The non-pathogenic magnetotactic bacteria Magnetosopirrillum gryphiswalense (MSR-1) was combined with antibiotic loaded mesoporous silica microtubes for targeting an infectious biofilm. Combining magnetic guidance property and swimming power of the MSR-1 cells, the biocomposite particles have been delivered to the matured E. coli (E. coli) biofilm followed by the antibiotic release and the biofilm disruption, revealing a potential for antibiofilm applications.

Xu et al. reported the development of an unprecedented sperm-hybrid micromotor for targeted drug delivery (Xu et al., 2018). This micromotor consists of a motile sperm cell which is both a propulsion source and a drug carrier (Figure 1). The other component is a 3D-printed magnetic tubular microstructure (called “tetrapod”) made of a polymer and coated with 10 nm Fe and 2 nm Ti (to protect Fe from oxidation). The tetrapod contains four arms which release the sperm cell in situ when they are pushed into a tumor. A magnetic field allows for controllable magnetic guidance as well as release, allowing drug delivery to tumor cells without damaging the healthy tissue. This system combines high drug loading capacity, self-propulsion, in situ mechanical trigger release of the drug-loaded sperm, sperm penetration ability, and improved drug availability.

FIGURE 1

www.frontiersin.orgFigure 1. (A) SEM images of an array of printed tetrapod microstructures. (B) Schematic illustrating the mechanical release mechanism. (C) Track (red line) of a sperm-hybrid motor under magnetic guidance in the horizontal and vertical planes. (D) Image sequence of a sperm release process when the arms hit the corner of a polydimethylsiloxane wall. Blue arrows point at the sperm head. Time lapse in min:s (Xu et al., 2018). Reproduced with the permission of the copyright holder [American Chemical Society].

In order to develop multifunctional NPs combining a near-infrared (NIR) plasmonic response with magnetic targeting, Tsai et al. deposited a double layer of Au/Ag alloy on the surface of truncated octahedral iron oxide NPs (Tsai et al., 2018). The rattle-shaped nanostructures exhibited a response for photothermal therapy (PTT) and magnetic guidance for hyperthermia and MRI as well as accumulation of the probes using an external magnetic field. The distance between the layers was controlled for maximum NIR absorption. These probes do not require a drug for chemotherapy as a dual action is already realized with PTT and hyperthermia.

Nanoparticle Clustering/Assembly

One of the primary issues with using superparamagnetic iron oxide NPs is that the individual NPs do not display high magnetization which is unfavorable for guiding them through the body (Kralj et al., 2017). A way to overcome this problem is clustering of NPs to increase their overall magnetic response. Zheng et al. synthesized copolymers of hyaluronic acid (HA) and C16 micelles using peptide formation followed by encapsulation of docetaxel (DTX, an anti-cancer agent) and NPs to develop multifunctional micelles (Zheng et al., 2018). HA is especially attractive because it binds to the CD-44 receptor which is overexpressed in various types of cancer in addition to its biocompatibility and biodegradability (Lee et al., 2012). Cellular uptake occurred via CD-44 receptor-mediated endocytosis and was enhanced by the presence of a magnetic field. This uptake method increases the amount of micelles in the tumor tissues compared to the normal tissues that creates a favorable contrast in MR images. Furthermore, drug release was triggered by NIR irradiation.

Assembly of iron oxide NPs on polydopamine (PDA) NPs allowed for an enhanced magnetic response and stimuli-controlled drug release for in vivo cancer theranostics (Ao et al., 2018). The high reactivity of the PDA surface furnishes a possibility for reduction-responsive prodrugs, while poly(ethylene glycol) (PEG) chains allow for in vivo cancer therapy. Due to a combination of MRI/photoacoustic dual-modal tumor imaging and controlled magnetic drug targeting, the effective tumor obliteration was accomplished via synergy of NIR photothermal ablation (due to PDA) and anticancer drug magnetic delivery.

Iron oxide NPs with the grafted poly(styrene)-b-poly(acrylic acid) (PS-b-PAA) block copolymer were self-assembled into multilayer magneto-vesicles (MVs) and utilized for incorporation of drugs in the hollow cavity (Yang et al., 2018). High packing density of iron oxide NPs in MVs allowed for the high magnetization and transverse relaxivity rate (r2) in MRI. When injected, DOX-loaded MVs conjugated with RGD peptides were efficiently accumulated in tumor cells due to magnetic targeting.

Innovative magnetic drug delivery vehicles were developed based on magnetite NP clusters (Wang, Y. et al., 2018). Two shells were built on the NP cluster surface: an inner shell of PDA with attached triphenylphosphonium (TPP) and an outer shell of methoxy PEG (mPEG) linked to PDA by disulfide bonds. At the first stage of targeting, the magnetic NP clusters allow for the bioprobe accumulation at the tumor site using an external magnetic field. At the second stage, mitochondrial targeting takes place as the mPEG shell is removed from the NPs by a redox reaction to expose TPP. Upon NIR irradiation at the tumor site, a photothermal effect is produced from the PDA photosensitizer, resulting in a strong decrease in mitochondrial membrane potential. At the same time, DOX is released, leading to the damage of mitochondrial DNA and cell death. Thus, photothermal therapy and chemotherapy are combined with magnetic drug delivery resulting in an enhancement of the DOX performance.

Magnetic Microbubbles

Image-guided and targeted modulation of drug delivery by external physical triggers at the site of pathology has been promising for drug targeting (Vlaskou et al., 2010Cai et al., 2012). Magnetic microbubbles (MagMB) that are responsive to magnetic and acoustic field changes and visible to ultrasonography were suggested for magnetic drug targeting. Recently, MagMB were prepared by mixing the suspension of protamine-functionalized microbubbles (MB-Prot) with the suspension of the heparinized NPs (Chertok and Langer, 2018). MagMB were gathered in tumor by magnetic targeting and observed by ultrasonography. Using focused ultrasound, MagMB were collapsed when necessary to release a drug. The authors demonstrated drug delivery to tumors could be enhanced by optimizing magnetic and acoustic fields, using ultrasonographic monitoring of MagMB in real-time.

Tang et al. synthesized multifunctional MagMB utilizing poly(lactic-co-glycolic acid) (PLGA), FA, perofluorohexane (PFH), Fe3O4, and DOX (Tang et al., 2018). These nanocomposites are able to move intravenously due to their initial nanometer-range size. However, when high-intensity focused ultrasound (HIFU) is used, PFH is transformed from the liquid to the gas phase due to an increase in temperature. The PFH gas forms microbubbles which enhance the ultrasound image. Fe3O4 allows for the nanocomposite to be efficiently targeted through MRI guidance. Additionally, the FA ligands on the surface of the nanocomposites specifically target the tumor cells via conjugation. The DOX release is triggered by HIFU exposure, and the release is accelerated due to the tumor-acidic microenvironment. Finally, Fe3O4 NPs enhance the sensitivity of the tumor via the hyperthermia effect (Moroz et al., 2001). This nanocomposite is an efficient and comprehensive theranostics probe.

Another multifunctional MagMB are based on magnetic liposomes (Liu et al., 2017a). Liposomes range in size from 50 to 1,000 nm and are biocompatible. Both water-soluble and water-insoluble drugs/NPs can be loaded into the core while maintaining high MRI contrast (Liu et al., 2017a). In magnetic liposomes synthesized by Yang et al. γ-Fe2O3 were encapsulated by liposomes doped with anethole ditholethione (Liu et al., 2017b). MR imaging was used to follow the accumulation of the magnetic liposomes in the tumor. Additionally, ultrasound was used to produce microbubbles (H2S) in order to ablate the tumor tissue via an increase in size (Liu et al., 2017b).

Magnetic Microcapsules

Magnetic multilayer microcapsules composed of poly(allylamine hydrochloride) and poly(sodium 4-styrenesulfonate) and prepared by LbL deposition were utilized as magnetic delivery vehicles in vitro and in vivo (Voronin et al., 2017in vivo experiments performed on mesenteric vessels of white mongrel rats reveal that capsules can be successfully trapped by the magnetic field and even stay there after the magnetic field is turned off. This work validates the effective control of microcapsules in a blood flow, making them promising drug delivery systems with remote navigation by the external magnetic field.

Microcapsules called iMushbots and prepared from mesoporous mushroom (Agaricus bisporus) fragments coated with magnetite NPs showed promising properties for targeted delivery (Bhuyan et al., 2017). The magnetite NPs played two roles (i) helping to pH-induced chemotaxis via the heterogeneous catalytic decomposition of the peroxide fuel in the presence of iron oxide and (ii) allowing a remote magnetic control of the iMushbot movement. The iMushbots also demonstrated higher drug retaining ability inside alkaline pH regions (human blood) and easy drug release in acidic medium (cancerous tissue) (Figure 2).

FIGURE 2

www.frontiersin.orgFigure 2. Schematic representation of the iMushbot action (Bhuyan et al., 2017). It is being reproduced with the permission of the copyright holder [American Chemical Society].

Magnetic Fibers

Polyvinyl alcohol fibers filled with magnetite NPs were synthesized via infusion gyration and studied as biocompatible magnetically triggered drug delivery vehicles (Perera et al., 2018). The authors demonstrated that acetaminophen (model drug) uploaded via impregnation can be controllably released by magnetic actuation. Moreover, upon creating a magnetic field 90% cumulative release was observed in 15 min which was much higher than that without magnetic field. These results demonstrate a potential for remote delivery of drugs or other substances.

Drug Uptake/Release

Uptake of drugs in magnetic drug delivery vehicles is carried out similar to non-magnetic carriers via conjugation (Chaudhary et al., 2015Pourmanouchehri et al., 2018), hydrophobic interactions (Cho et al., 2018), absorption within porous structures (Kakar et al., 2013), etc. The drug release can be triggered by pH changes in the microenvironment (Wang et al., 2017Wei et al., 2017Wang, G. et al., 2018), by mechanical forces (Xu et al., 2018), NIR irradiation (Wang, Y. et al., 2018Zheng et al., 2018), chemical reduction (Ao et al., 2018), HIFU (Moroz et al., 2001), and magnetic hyperthermia (Cho et al., 2018).

Cytotoxicity

Cytotoxity of DOX bearing magnetic bioprobes has been discussed in a number of publications both for cancer cells and for healthy tissues (Lee et al., 2017Ao et al., 2018Sun, Q. et al., 2018). Cytotoxicity toward healthy cells is limited because most systems are localized and made biocompatible. It is demonstrated that the bioprobes without DOX do not kill cancer cells (Ao et al., 2018), while efficacy of magnetic bioprobes with DOX is comparable to that of free DOX (Ao et al., 2018). Cytotoxicity also increases with increasing amounts of DOX and/or upon NIR irradiation (Sun, Q. et al., 2018).

Approaches to Magnetic Drug Targeting

External Magnetic Field

In the majority of cases, the magnetic drug targeting/delivery is realized upon the application of an external magnetic field from electromagnetic coils (Hoshiar et al., 2017) or various types of permanent magnets (Carenza et al., 2014Price et al., 2017Shaw et al., 2017Venugopal et al., 2017Voronin et al., 2017Shamsi et al., 2018). It was demonstrated that magnet geometry and tumor-magnet distance can be of crucial importance for the effective magnetic drug delivery (Shamsi et al., 2018Wang, X. et al., 2018).

Delivery Deep Inside the Body

Utilizing stationary external magnets to attract the magnetic drug carriers, it is difficult to target areas below 5 cm under the skin. A dynamic control of magnets to focus magnetic carriers to deep tissue targets has been proposed (Shapiro, 2009). Using first-principles magneto-statics and ferrofluid transport model, the author demonstrated that a sequence of actuations can push magnetic NPs through a center region, thus generating a focus at a deep target. In the other theoretical work, by rotating the magnet and setting a central axis to the target part, ferromagnetic drugs were accumulated in the target (Chuzawa et al., 2013). However, to the best of our knowledge no experimental studies have confirmed the conclusions of the theoretical work.

Magnetic Implants

Instead of using an external magnetic field which could be problematic in the case of delivery to some organs, magnetic implants seem to be a viable alternative. Ge et al. reported targeted drug delivery to a biocompatible magnetic implant scaffold made of a magnetite/poly(lactic-co-glycolic acid) nanocomposite (Ge et al., 2017). In this case, a drug was attached to magnetic NPs to create a driving force for delivery. Such magnetic implants can be promising for a bone cancer, providing a precise cancer treatment. Magnetic implants can be imbedded in a fatty tissue to treat obesity (Saatchi et al., 2017) and in the inner ear to treat deafness (Le et al., 2017).

Summary and Outlook

In summary, we can identify several essential rules which need to be followed for the development of successful magnetic drug delivery vehicles. The magnetic bioprobes need to be sufficiently large to possess high magnetization for efficient magnetic targeting. They have to allow for controlled drug uptake and release mechanisms to make them efficient delivery systems. Finally, they have to possess theranostic features (both diagnostic and therapeutic) to enhance the delivery and the drug action. The other key feature of promising magnetic drug delivery vehicles is long-circulating, stealthy systems which will not be cleared by a phagocyte system (Zhang et al., 20172018). This can be realized by a combination of peptides and polymers in the particle outer shells. It is worth noting, however, that the degree of bioprobe sophistication is only warranted by the wealth of properties it delivers, as sometimes simpler systems can be quite satisfactory and less expensive.

It is worth noting that despite FDA approval and commercialization of iron oxide based bioprobes for MRI and hyperthermia, clinical trials of magnetic drug delivery received less attention. To the best of our knowledge, there were several small clinical trials (even in Phase III), but none resulted in FDA approval or commercialization (Wang et al., 2013Min et al., 2015Ulbrich et al., 2016).

We believe that the major unsolved problem in magnetic drug delivery is the absence of mechanisms for delivery into the depth of the body. The recent strategy of magnetic or magnetiziable implants seems to be promising but it requires a surgical intervention and in some cases cannot be implemented. Currently, efforts from physicists and engineers are required to move this field forward to real life applications.

Author Contributions

PP carried out analysis of the literature and wrote a part on magnetic bioprobe synthesis. WM collected the literature and wrote the rest of the discussion on magnetic bioprobes. AA-G wrote part on approaches to magnetic targeting. LB wrote all other sections and oversaw the project.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

Ao, L., Wu, C., Liu, K., Wang, W., Fang, L., Huang, L., et al. (2018). Polydopamine-derivated hierarchical nanoplatforms for efficient dual-modal imaging-guided combination in vivo cancer therapy. ACS Appl. Mater. Interfaces 10, 12544–12552. doi: 10.1021/acsami.8b02973

PubMed Abstract | CrossRef Full Text | Google Scholar

Biden and Co-Conspirators Want 15% of the World’s Money For the U.N.

G7 backs Biden’s sweeping overhaul of global tax system

[Forcing a global tax of 15%, in addition to regular national income taxes…ask Biden (Who will ask Obama). ]

  • Under the agreement, G-7 nations will back a global minimum corporate tax of at least 15%, U.K. Finance Minister Rishi Sunak announced in a series of tweets.
  • The reforms will affect the largest companies in the world with profit margins of at least 10%.
  • U.S. Treasury Secretary Janet Yellen, who is in London for the face-to-face meeting, hailed the move as significant and unprecedented.
Britain's Chancellor of the Exchequer Rishi Sunak (from left), U.S. Treasury Secretary Janet Yellen, Managing Director of the IMF Kristalina Georgieva and Canada's Finance Minister Chrystia Freeland chatting on the first day of the Group of Seven Finance
Britain’s Chancellor of the Exchequer Rishi Sunak (from left), U.S. Treasury Secretary Janet Yellen, Managing Director of the IMF Kristalina Georgieva and Canada’s Finance Minister Chrystia Freeland chatting on the first day of the Group of Seven Finance Ministers Meeting at Lancaster House in London on June 4, 2021.
Stefan Rousseau | AFP | Getty Images
LONDON — The finance ministers of the most advanced economies, known as the Group of Seven, have backed a U.S. proposal that calls for corporations around the world to pay at least a 15% tax on earnings.

“G-7 finance ministers today, after years of discussions, have reached a historic agreement to reform the global tax system, to make it fit for the global digital age — and crucially to make sure that it’s fair so that the right companies pay the right tax in the right places,” U.K. Finance Minister Rishi Sunak announced in a video statement on Saturday.

If finalized, it would represent a significant development in global taxation. Members of the G-7, which include Canada, France, Germany, Italy, Japan, the U.K. and the U.S., will convene for a summit in Cornwall, U.K., next week.

An agreement among this group would provide needed momentum for upcoming talks planned with 135 countries in Paris. Finance ministers from the Group of 20 are also expected to meet in Venice in July.

“We commit to reaching an equitable solution on the allocation of taxing rights, with market countries awarded taxing rights on at least 20% of profit exceeding a 10% margin for the largest and most profitable multinational enterprises,” according to a statement from the G-7 finance ministers.

“We will provide for appropriate coordination between the application of the new international tax rules and the removal of all Digital Services Taxes, and other relevant similar measures, on all companies,” it said.

U.S. Treasury Secretary Janet Yellen, who is in London for the face-to-face meeting, hailed the move as significant and unprecedented.

“That global minimum tax would end the race-to-the-bottom in corporate taxation, and ensure fairness for the middle class and working people in the U.S. and around the world,” she tweeted.

President Joe Biden and his administration had initially suggested a minimum global tax rate of 21% in an attempt to prevent countries luring international businesses with low or zero taxes. However, after tough negotiations, a compromise was reached to set the bar at 15%.

A global deal in this field would be good news for cash-strapped nations, who are trying to rebuild their economies after the coronavirus crisis.

But Biden’s idea had not been received with the same level of excitement across the world. The U.K., for example, did not immediately voice its support for the proposal.

U.S. President Joe Biden speaks during a meeting with a bipartisan group of members of Congress.
U.S. President Joe Biden speaks during a meeting with a bipartisan group of members of Congress.
Pool | Getty Images News | Getty Images

The issue can be contentious within the European Union as well, where various member states charge different corporate tax rates and can attract big-name firms by doing so. Ireland’s tax rate, for example, is 12.5%, while France’s can be as high as 31%.

Speaking in April, Irish Finance Minister Paschal Donohoe said smaller nations should be allowed to have lower tax rates given that they don’t have the same capacity for scale as the larger economies do, the U.K.’s Guardian newspaper reported.

The world’s most powerful economies have been at odds over taxation for some time, in particular in the wake of plans to tax digital giants more.

The U.S., under former President Donald Trump, vehemently opposed digital tax initiatives in different countries and threatened to impose trade tariffs against countries that would plan on taxing U.S. tech companies.

Some major firms across the world reacted positively the agreement on Saturday. Nick Clegg, vice president of global affairs at Facebook, wrote in a tweet that the company welcomed the G-7 tax rule.

“We want the international tax reform process to succeed and recognize this could mean Facebook paying more tax, and in different places,” Clegg wrote.

Google spokesman Jose Castaneda told CNBC in a statement that the company supports efforts to update international tax rules. “We hope countries continue to work together to ensure a balanced and durable agreement will be finalized soon,” he said.

White House and Media Block Serious Wuhan Investigations For Fear of Helping Trump

“That is an extraordinarily damning admission. Health experts who understood all along that it was entirely possible that the virus emerged from a lab simply refused to examine the hypothesis because it had become associated with the likes of Donald Trump.”
Photo: Ng Han Guan/AP/Shutterstock
As we sift through the lab-leak debacle, the good news is that the healthy antibodies in the system are still strong enough to overcome the groupthink that produced the original error. News media are investigating a hypothesis they once dismissed, and the government has announced an investigation to find the truth.

The bad news is that the problem is turning out to be worse than it initially seemed — and worse still, the source of the failure is not going away. The implications of this episode are much broader than understanding the source of the pandemic. It is a question about whether institutions like the media and government can withstand the pressure of ideological conformity.

A recent Washington Post story, looking back at the government’s response to virus’s origination, reported that many officials refused to explore the lab-leak hypothesis because it was associated with right-wing politics. “For some of the officials who were privately suspicious of the Wuhan lab, Trump’s and Navarro’s comments turned the lab-leak scenario into a fringe conspiracy theory,” the Post found, “It became nearly impossible to generate interest among health experts in a hypothesis that Trump had turned into a political weapon, they said.”

That is an extraordinarily damning admission. Health experts who understood all along that it was entirely possible that the virus emerged from a lab simply refused to examine the hypothesis because it had become associated with the likes of Donald Trump.

Katherine Eban, writing in Vanity Fair, has written a lengthy exposé drawing out the failure in detail. One State Department official wrote that his team was warned not to investigate the origins of the pandemic because it would “open a can of worms.” Miles Yu, the State Department’s principal China strategist, tells Eban, “Anyone who dares speak out would be ostracized.” After former CDC head Robert Redfield said he believed the virus originated in a lab, he tells Eban “I was threatened and ostracized because I proposed another hypothesis.”

In retrospect, the error is clear enough all along. The origins of the pandemic were always murky, and the strongest reason to dismiss lab-leak out of hand — that the Wuhan lab supposedly had airtight security protocols — was more rumor than fact. What’s more, the notion that the theory was “racist” was always transparently dubious. A story in which the virus emerged from failed safety protocols at the Wuhan lab is not inherently more racist than a theory in which it emerged from a wet market. (If anything, blaming the pandemic on China’s people for eating bats lends itself much more easily to racism than blaming China’s government for lax security at its research labs.)

Journalists make mistakes, especially operating in a chaotic atmosphere dominated by the ceaseless jabberings of a pathological liar with a giant megaphone. What’s concerning is that, even faced with undeniable proof of the error, many people still refuse to concede it.

An article in Nature warns against a a “divisive” investigation into the virus’s origins. Remarkably enough, given that it comes from a scientific journal, the article does not directly question the possibility that COVID did escape from a lab. Instead, it warns that the investigation is “fueling online bullying of scientists and anti-Asian harassment in the United States, as well as offending researchers and authorities in China whose cooperation is needed.” One scientist who reports this “bullying” is Canadian virologist Angela Rasmussen, who in 2020 had developed a high-profile Twitter presence laced with confident dismissals of lab-leak hypothesis as a “conspiracy theory” that was “steeped in racist stereotypes.”

When scientists are openly arguing against the study of a scientific hypothesis, for non-scientific reasons, something has gone haywire. In this case, that something seems to be a hothouse atmosphere centered around social media, that has cultivated an ethos of moral fervor and political homogeneity.

“Personally I think that when a public figure is a known racist liar it’s fine to treat their evidence-free statements as racist lies,” insisted podcaster Michael Hobbes. “If David Duke gives a speech about rising urban crime rates it’s not the media’s job to report the most plausible version of his argument.” Writer and University of Minnesota Law School fellow Will Stancil called renewed attention to the lab-leak hypothesis “the latest example of hybridization between the right-wing fever swamps and the white guys who run journalism.”

The notable aspect of these statements is not the conclusion but the logic that produced it. That journalists dismissed a plausible theory, because they associated it with people who have noxious beliefs, does not strike them as a problem, but a correct epistemological model.

++

Jonathan Last, an apostate conservative writing for the Bulwark (a new magazine that serves as a kind of refuge for Republican and conservative intellectuals unable to stomach Donald Trump), recently made an observation about conservatives taunting the mainstream media for dismissing the lab-leak hypothesis. Yes, Last allowed, many outlets got the story wrong by describing the hypothesis that COVID-19 escaped from the lab in Wuhan, rather than the nearby wet market, as a false, racist conspiracy theory, when in truth they never really knew the virus’s origins. But most of those outlets have since corrected their error and treated the issue as a live scientific mystery. When has conservative media ever engaged in anything like this sort of self-correction? Is Fox News running self-flagellating segments questioning, say, the network’s promotion of hydroxychloroquine as a proven COVID treatment? The very thought is a punchline.

This asymmetry between the mainstream news media and the conservative media that was created to oppose it has long been a source of satisfaction for we liberals. Modern journalism, like think tanks and the bureaucracy, grew out of a Progressive Era belief in disinterested expertise. Guided by the principles of scientific inquiry, these institutions would follow the truth wherever it led.

The conservative movement built a counter-Establishment to oppose this network, but the alt-institutions of the right mimicked the hallowed liberal Establishment only in form. The Heritage Institution, the Washington Times, and Fox News were not mirror images of Brookings, the New York Times, and CBS News — they were parodies of them. Liberals had a phrase to describe this imbalance: the hack gap. The Republican Party had an army of partisans at its disposal, unburdened by any fealty to any scientific or professional norms save the advancement of the conservative movement. The liberal media might make mistakes, and bureaucracies may produce wrong conclusions, but at least they aspire to norms of fairness and impartiality that the right-wing counterparts merely sneer at.

Openness to evidence is the historical strength of American liberalism. This is why, for all the errors liberals have committed since the Progressive Era, a capacity for self-correction has given continued vitality to their — our — creed. The lab-leak fiasco ought to be a warning sign of what happens if the urge to not be defeated or manipulated by the right turns into an emulation of its methods. The only thing worse than having a hack gap would be not having one.