Anti-PEG antibodies boosted in humans by SARS-CoV-2 lipid nanoparticle mRNA vaccine

Humans commonly have low level antibodies to poly(ethylene) glycol (PEG) due to environmental exposure. Lipid nanoparticle mRNA vaccines for SARS-CoV-2 contain small amounts of PEG but it is not known if PEG antibodies are enhanced by vaccination and if there are any consequences. We studied plasma from 55 people receiving the Comirnaty (Pfizer-BioNTech) mRNA vaccine for PEG-specific antibodies. Anti-PEG IgG was commonly detected prior to vaccination and was boosted a mean of 1.78-fold (range 0.68 to 16.6) by vaccination. Anti-PEG IgM increased 2.64-fold (0.76 to 12.84) following vaccination. PEG antibodies did not impact the neutralizing antibody response to vaccination. Pre-existing levels of anti-PEG IgM correlated with increased reactogenicity. A rise in PEG antibodies following vaccination was associated with an increase in the association of PEG-based nanoparticles to blood immune cells ex vivo. We conclude that low level PEG-specific antibodies can be modestly boosted by a lipid nanoparticle mRNA-vaccine and that PEG-specific antibodies are associated with higher reactogenicity. The longer-term clinical impact of the increase in PEG-specific antibodies induced by lipid nanoparticle mRNA-vaccines should be monitored.

Intracellular Reduction-Responsive Molecular Targeted Nanomedicine for Hepatocellular Carcinoma Therapy

The stimuli-responsive polymer-based platform for controlled drug delivery has gained increasing attention in treating hepatocellular carcinoma (HCC) owing to the fascinating biocompatibility and biodegradability, improved antitumor efficacy, and negligible side effects recently. Herein, a disulfide bond-contained polypeptide nanogel, methoxy poly(ethylene glycol)−poly(l-phenylalanine-co-l-cystine) [mPEG−P(LP-co-LC)] nanogel, which could be responsive to the intracellular reduction microenvironments, was developed to deliver lenvatinib (LEN), an inhibitor of multiple receptor tyrosine kinases, for HCC therapy. The lenvatinib-loaded nanogel (NG/LEN) displayed concise drug delivery under the stimulus of glutathione in the cancer cells. Furthermore, the intracellular reduction-responsive nanomedicine NG/LEN showed excellent antitumor effect and almost no side effects toward both subcutaneous and orthotopic HCC tumor-allografted mice in comparison to free drug. The excellent tumor-inhibition efficacy with negligible side effects demonstrated the potential of NG/LEN for clinical molecular targeted therapy of gastrointestinal carcinoma in the future.

Fabrication of Low-Fouling Surfaces on Alkyne-Functionalized Poly-(p-xylylenes) Using Click Chemistry

A facial, versatile, and universal method that breaks the substrate limits is desirable for antifouling treatment. Thin films of functional poly-p-xylylenes (PPX) that are deposited using chemical vapor deposition (CVD) provide a powerful platform for surface immobilization of molecules. In this study, we prepared an alkyne-functionalized PPX coating on which poly (sulfobetaine methacrylate-co-Az) could be conjugated via click chemistry. We found that the conjugated polymers were very stable and inhibited cell adhesion and protein adsorption effectively. The same conjugation strategy could also be applied to conjugate azide-containing poly (ethylene glycol) and poly (NIPAAm). The results indicate that our method provides a simple and robust tool for fabricating antifouling surfaces on a wide range of substrates using CVD technology of functionalized poly (p-xylylenes) for biosensor, diagnostics, immunoassay, and other biomaterial applications.