Potent Virustatic Polymer–Lipid Nanomimics Block Viral Entry and Inhibit Malaria Parasites In Vivo

Abstract

Infectious diseases continue to pose a substantial burden on global populations, requiring innovative broad-spectrum prophylactic and treatment alternatives. Here, we have designed modular synthetic polymer nanoparticles that mimic functional components of host cell membranes, yielding multivalent nanomimics that act by directly binding to varied pathogens. Nanomimic blood circulation time was prolonged by reformulating polymer–lipid hybrids. Femtomolar concentrations of the polymer nanomimics were sufficient to inhibit herpes simplex virus type 2 (HSV-2) entry into epithelial cells, while higher doses were needed against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Given their observed virustatic mode of action, the nanomimics were also tested with malaria parasite blood-stage merozoites, which lose their invasive capacity after a few minutes. Efficient inhibition of merozoite invasion of red blood cells was demonstrated both in vitro and in vivo using a preclinical rodent malaria model. We envision these nanomimics forming an adaptable platform for developing pathogen entry inhibitors and as immunomodulators, wherein nanomimic-inhibited pathogens can be secondarily targeted to sites of immune recognition.

Block Length‐Dependent Protein Fouling on Poly(2‐oxazoline)‐Based Polymersomes: Influence on Macrophage Association and Circulation Behavior

“…FCS is a highly sensitive method for detecting nanoparticle loading/release, surface functionalization, enzyme kinetics and protein binding, including measurement of in situ protein corona formation (no purification needed). [ 54–57 ]…”

Revealing Population Heterogeneity in Vesicle-Based Nanomedicines Using Automated, Single Particle Raman Analysis

“…SPARTA measurements were performed either on a custom system as previously described or on the SPARTA alpha prototype. , 200 μL of particle suspension was placed on a 22 mm diameter coverglass (VWR) affixed to a microscope slide, and a 63× 1.0 NA water immersion lens (W Plan Apochromat, Zeiss) was immersed in the droplet. For polymersomes, each trapped particle was measured for 20 s before 1 s laser shuttering to allow particle release and diffusion of a new particle into the confocal volume.…”

“…This high-throughput nature of SPARTA improves the reliability of the data and offers representative population data at the single particle level. Since its establishment, the SPARTA technique has been used for composition analysis of liposomes and polymersomes, − reaction monitoring of nanoparticle functionalization and determining nanoparticle permeability . However, it has not yet been used for detailed characterization of nanomedicine loading heterogeneity or cargo loading location.…”

Progress in Treatment and Diagnostics of Infectious Disease with Polymers

“…The results demonstrate a potent virustatic role of nanomimics in all types of targeted parasites that was tested with a rodent mouse model. 165 Model Organs and Clinical and Preclinical Status of Antimalarial Vaccines. For treatment of malaria standard mouse models are C57BL/6 and CBA/T6 and parasite strains are P. yoelli and P. berghei.…”