Biodegradable Polyester Nanoparticle Vaccines Deliver Self-Amplifying mRNA in Mice at Low Doses

Delivery of self-amplifying mRNA (SAM) has high potential for infectious disease vaccination due to its self-adjuvanting and dose-sparing properties. Yet a challenge is the susceptibility of SAM to degradation and the need for SAM to reach the cytosol fully intact to enable self-amplification. Lipid nanoparticles are successfully deployed at incredible speed for mRNA vaccination, but aspects such as cold storage, manufacturing, efficiency of delivery, and the therapeutic window can benefit from further improvement. To investigate alternatives to lipid nanoparticles, a class of >200 biodegradable end-capped lipophilic poly(beta-amino ester)s (PBAEs) that enable efficient delivery of SAM in vitro and in vivo as assessed by measuring expression of SAM encoding reporter proteins is developed. The ability of these polymers to deliver SAM intramuscularly in mice is evaluated, and a polymer-based formulation that yields up to 37-fold higher intramuscular (IM) expression of SAM compared to injected naked SAM is identified. Using the same nanoparticle formulation to deliver a SAM encoding rabies virus glycoprotein, the vaccine elicits superior immunogenicity compared to naked SAM delivery, leading to seroconversion in mice at low RNA injection doses. These biodegradable nanomaterials may be useful in the development of next-generation RNA vaccines for infectious diseases.Copyright © 2023 The Authors. Advanced Therapeutics published by Wiley-VCH GmbH.

Macrophage membrane-biomimetic adhesive polycaprolactone nanocamptothecin for improving cancer-targeting efficiency and impairing metastasis

The recent remarkable success and safety of mRNA lipid nanoparticle technology for producing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has stimulated intensive efforts to expand nanoparticle strategies to treat various diseases. Numerous synthetic nanoparticles have been developed for pharmaceutical delivery and cancer treatment. However, only a limited number of nanotherapies have enter clinical trials or are clinically approved. Systemically administered nanotherapies are likely to be sequestered by host mononuclear phagocyte system (MPS), resulting in suboptimal pharmacokinetics and insufficient drug concentrations in tumors. Bioinspired drug-delivery formulations have emerged as an alternative approach to evade the MPS and show potential to improve drug therapeutic efficacy. Here we developed a biodegradable polymer-conjugated camptothecin prodrug encapsulated in the plasma membrane of lipopolysaccharide-stimulated macrophages. Polymer conjugation revived the parent camptothecin agent (e.g., 7-ethyl-10-hydroxy-camptothecin), enabling lipid nanoparticle encapsulation. Furthermore, macrophage membrane cloaking transformed the nonadhesive lipid nanoparticles into bioadhesive nanocamptothecin, increasing the cellular uptake and tumor-tropic effects of this biomimetic therapy. When tested in a preclinical murine model of breast cancer, macrophage-camouflaged nanocamptothecin exhibited a higher level of tumor accumulation than uncoated nanoparticles. Furthermore, intravenous administration of the therapy effectively suppressed tumor growth and the metastatic burden without causing systematic toxicity. Our study describes a combinatorial strategy that uses polymeric prodrug design and cell membrane cloaking to achieve therapeutics with high efficacy and low toxicity. This approach might also be generally applicable to formulate other therapeutic candidates that are not compatible or miscible with biomimetic delivery carriers. © 2022 The Authors

Assessment of Biofortification Approaches Used to Improve Micronutrient-Dense Plants That Are a Sustainable Solution to Combat Hidden Hunger.

Malnutrition causes diseases, immune system disorders, deterioration in physical growth, mental development, and learning capacity worldwide. Micronutrient deficiency, known as hidden hunger, is a serious global problem. Biofortification is a cost-effective and sustainable agricultural strategy for increasing the concentrations or bioavailability of essential elements in the edible parts of plants, minimizing the risks of toxic metals, and thus reducing malnutrition. It has the advantage of delivering micronutrient-dense food crops to a large part of the global population, especially poor populations. Agronomic biofortification and biofertilization, traditional plant breeding, and optimized fertilizer applications are more globally accepted methods today; however, genetic biofortification based on genetic engineering such as increasing or manipulating (such as CRISPR-Cas9) the expression of genes that affect the regulation of metal homeostasis and carrier proteins that serve to increase the micronutrient content for higher nutrient concentration and greater productivity or that affect bioavailability is also seen as a promising high-potential strategy in solving this micronutrient deficiency problem. Data that micronutrients can help strengthen the immune system against the COVID-19 pandemic and other diseases has highlighted the importance of tackling micronutrient deficiencies. In this study, biofortification approaches such as plant breeding, agronomic techniques, microbial fertilization, and some genetic and nanotechnological methods used in the fight against micronutrient deficiency worldwide were compiled.

Exploitation of polyphenols and proteins using nanoencapsulation for anti-viral and brain boosting properties - Evoking a synergistic strategy to combat COVID-19 pandemic.

The world is currently under the threat of COVID pandemic and has focused every dimension of research in finding a cure to this novel disease. In this current situation, people are facing mental stress, agony, fear, depression and other associated symptoms which are taking a toll on their overall mental health. Nanoencapsulation of certain brain boosting polyphenols including quercetin, caffeine, cocoa flavanols and proteins like lectins can become new area of interest in the present scenario. Besides the brain boosting benefits, we have also highlighted the anti- viral activities of these compounds which we assume can play a possible role in combating COVID-19 given to their previous history of action against certain viruses. This review outlines the nanoencapsulation approaches of such synergistic compounds as a novel strategy to take the ongoing research a step ahead and also provides a new insight in bringing the role of nanotechnology in addressing the issues related to COVID pandemic.