White Blood Cell Membrane-Coated Nanoparticles: Recent Development and Medical Applications.

White blood cells (WBCs) are immune cells that play essential roles in critical diseases including cancers, infections, and inflammatory disorders. Their dynamic and diverse functions have inspired the development of WBC membrane-coated nanoparticles (denoted "WBC-NPs"), which are formed by fusing the plasma membranes of WBCs, such as macrophages, neutrophils, T cells, and natural killer cells, onto synthetic nanoparticle cores. Inheriting the entire source cell antigens, WBC-NPs act as source cell decoys and simulate their broad biointerfacing properties with intriguing therapeutic potentials. Herein, the recent development and medical applications of WBC-NPs focusing on four areas, including WBC-NPs as carriers for drug delivery, as countermeasures for biological neutralization, as nanovaccines for immune modulation, and as tools for the isolation of circulating tumor cells and fundamental research is reviewed. Overall, the recent development and studies of WBC-NPs have established the platform as versatile nanotherapeutics and tools with broad medical application potentials.

Nanoparticle approaches against SARS-CoV-2 infection.

Coronavirus disease 2019 (COVID-19), caused by the highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become the worst pandemic disease of the current millennium. To address this crisis, therapeutic nanoparticles, including inorganic nanoparticles, lipid nanoparticles, polymeric nanoparticles, virus-like nanoparticles, and cell membrane-coated nanoparticles, have all offered compelling antiviral strategies. This article reviews these strategies in three categories: (1) nanoparticle-enabled detection of SARS-CoV-2, (2) nanoparticle-based treatment for COVID-19, and (3) nanoparticle vaccines against SARS-CoV-2. We discuss how nanoparticles are tailor-made to biointerface with the host and the virus in each category. For each nanoparticle design, we highlight its structure-function relationship that enables effective antiviral activity. Overall, nanoparticles bring numerous new opportunities to improve our response to the current COVID-19 pandemic and enhance our preparedness for future viral outbreaks.

Surface Glycan Modification of Cellular Nanosponges to Promote SARS-CoV-2 Inhibition.

Cellular binding and entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are mediated by its spike glycoprotein (S protein), which binds with not only the human angiotensin-converting enzyme 2 (ACE2) receptor but also glycosaminoglycans such as heparin. Cell membrane-coated nanoparticles ("cellular nanosponges") mimic the host cells to attract and neutralize SARS-CoV-2 through natural cellular receptors, leading to a broad-spectrum antiviral strategy. Herein, we show that increasing surface heparin density on the cellular nanosponges can promote their inhibition against SARS-CoV-2. Specifically, cellular nanosponges are made with azido-expressing host cell membranes followed by conjugating heparin to the nanosponge surfaces. Cellular nanosponges with a higher heparin density have a larger binding capacity with viral S proteins and a significantly higher inhibition efficacy against SARS-CoV-2 infectivity. Overall, surface glycan engineering of host-mimicking cellular nanosponges is a facile method to enhance SARS-CoV-2 inhibition. This approach can be readily generalized to promote the inhibition of other glycan-dependent viruses.

Nanodelivery of STING agonists against cancer and infectious diseases.

Vaccination is a modality that has been widely explored for the treatment of various diseases. To increase the potency of vaccine formulations, immunostimulatory adjuvants have been regularly exploited, and the stimulator of interferon genes (STING) signaling pathway has recently emerged as a remarkable therapeutic target. STING is an endogenous protein on the endoplasmic reticulum that is a downstream sensor to cytosolic DNA. Upon activation, STING initiates a series of intracellular signaling cascades that ultimately generate potent type I interferon-mediated immune responses. Both natural and synthetic agonists have been used to stimulate the STING pathway, but they are usually administered locally due to low bioavailability, instability, and difficulty in bypassing the plasma membrane. With excellent pharmacokinetic profiles and versatility, nanocarriers can address many of these challenges and broaden the application of STING vaccines. Along these lines, STING-inducing nanovaccines are being developed to address a wide range of diseases. In this review, we discuss the recent advances in STING nanovaccines for anticancer, antiviral, and antibacterial applications.

ACE2 Receptor-Modified Algae-Based Microrobot for Removal of SARS-CoV-2 in Wastewater.

The coronavirus SARS-CoV-2 can survive in wastewater for several days with a potential risk of waterborne human transmission, hence posing challenges in containing the virus and reducing its spread. Herein, we report on an active biohybrid microrobot system that offers highly efficient capture and removal of target virus from various aquatic media. The algae-based microrobot is fabricated by using click chemistry to functionalize microalgae with angiotensin-converting enzyme 2 (ACE2) receptor against the SARS-CoV-2 spike protein. The resulting ACE2-algae-robot displays fast (>100 µm/s) and long-lasting (>24 h) self-propulsion in diverse aquatic media including drinking water and river water, obviating the need for external fuels. Such movement of the ACE2-algae-robot offers effective "on-the-fly" removal of SARS-CoV-2 spike proteins and SARS-CoV-2 pseudovirus. Specifically, the active biohybrid microrobot results in 95% removal of viral spike protein and 89% removal of pseudovirus, significantly exceeding the control groups such as static ACE2-algae and bare algae. These results suggest considerable promise of biologically functionalized algae toward the removal of viruses and other environmental threats from wastewater.

Nanotechnology for virus treatment.

The continued emergence of novel viruses poses a significant threat to global health. Uncontrolled outbreaks can result in pandemics that have the potential to overburden our healthcare and economic systems. While vaccination is a conventional modality that can be employed to promote herd immunity, antiviral vaccines can only be applied prophylactically and do little to help patients who have already contracted viral infections. During the early stages of a disease outbreak when vaccines are unavailable, therapeutic antiviral drugs can be used as a stopgap solution. However, these treatments do not always work against emerging viral strains and can be accompanied by adverse effects that sometimes outweigh the benefits. Nanotechnology has the potential to overcome many of the challenges facing current antiviral therapies. For example, nanodelivery vehicles can be employed to drastically improve the pharmacokinetic profile of antiviral drugs while reducing their systemic toxicity. Other unique nanomaterials can be leveraged for their virucidal or virus-neutralizing properties. In this review, we discuss recent developments in antiviral nanotherapeutics and provide a perspective on the application of nanotechnology to the SARS-CoV-2 outbreak and future virus pandemics.

Cellular Nanosponges Inhibit SARS-CoV-2 Infectivity.

We report cellular nanosponges as an effective medical countermeasure to the SARS-CoV-2 virus. Two types of cellular nanosponges are made of the plasma membranes derived from human lung epithelial type II cells or human macrophages. These nanosponges display the same protein receptors, both identified and unidentified, required by SARS-CoV-2 for cellular entry. It is shown that, following incubation with the nanosponges, SARS-CoV-2 is neutralized and unable to infect cells. Crucially, the nanosponge platform is agnostic to viral mutations and potentially viral species, as well. As long as the target of the virus remains the identified host cell, the nanosponges will be able to neutralize the virus.