Nanomaterial Strategies for Delivery of Therapeutic Cargoes

Abstract

Over the last decade, much progress has been made in developing nanoparticle-mediated delivery systems to overcome the limitations of existing in vivo delivery technologies. However, the balance between efficacy and safety continues to limit the clinical translation of nanoscale delivery systems. Furthermore, optimizing delivery efficiency requires tuning nanoparticle type and attachment chemistry, both of which are dependent on the cargo being delivered. While the delivery of protein therapeutics is of particular interest, the complexity inherent to protein cargo introduces additional challenges for cargo loading and stabilization. Advances needed for efficient and safe in vivo nanoparticle delivery systems should prioritize design strategies that co-optimize safety, biodegradability, and covalent functionalization. In this review, the most commonly used non-viral nanoparticles are outlined for delivery of small molecule drug, nucleic acid, and protein therapeutic cargoes and potential strategies are discussed for rationally designing nanoparticle-mediated delivery systems.

Tannic Acid Lipid Nanoparticles can Deliver Messenger RNA Payloads and Improve their Endosomal Escape

“…Nucleic acid sequences can be rapidly engineered to silence, augment, or replace defective genes in the body. [1][2][3][4][5][6][7] Accordingly, the usage of nucleic acids as drugs has emerged as an attractive strategy to prevent and treat disease. [8][9][10][11][12][13][14][15] Despite their therapeutic potential, many nucleic acids are unable to act therapeutically unless they can enter target cells in the body.…”

An Efficacy and Mechanism Driven Study on the Impact of Hypoxia on Lipid Nanoparticle Mediated mRNA Delivery

“…mRNA drugs are a powerful yet sensitive class of genetic medicines with application in vaccination, protein replacement, genome editing, and cellular reprogramming, amongst other therapeutic areas. − What makes mRNA drugs so powerful is that their sequence can be easily reprogrammed to instruct the body to produce therapeutic proteins using the body’s native cellular machinery; what makes mRNA drugs so sensitive is that they are susceptible to degradation inside and outside of the body, are immunogenic, and are poorly internalized by target cells. , Accordingly, mRNA drugs require carrier systems to ensure they can be delivered to the correct location in the body, at the right dose, and for the appropriate amount of time. Recently, lipid nanoparticles (LNPs) have emerged as a frontrunner class of delivery vehicles for translational mRNA therapy following the clinical approval of the Moderna and Pfizer/BioNTech COVID-19 vaccines. − In addition to having the ability to deliver mRNA to cell populations in vitro and in vivo, LNPs also offer a “plug-and-play” approach that easily allows for a cell-type specific LNP to deliver different mRNAs encoding for multiple types of therapeutic proteins.…”

Importance of Standardizing Analytical Characterization Methodology for Improved Reliability of the Nanomedicine Literature

“…One can assume that if unreliability or lack of reproducibility [ 10 – 12 ] were the major barriers in nanomedicine, few products would pass through the regulatory pipeline to reach the market. However, an increasingly large number of medical products using nanotechnology have reached the market, comprising a multi-billion dollar industry, such as the recently developed SARS-CoV2 vaccine formulations by Moderna and Pfizer/BioNTech among others [ 13 ]. More generally, according to the FDA database of medical devices, about 2586 different 'nano' medical devices were sold in the USA from 1980 to 2017 [ 14 ].…”