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Surface Functionalization of Hepatitis E Virus Nanoparticles Using Chemical Conjugation Methods

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Physalis Mottle Virus-Like Nanocarriers with Expanded Internal Loading Capacity.

Krister J Barkovich¹, Zhuohong Wu^2,3, Zhongchao Zhao^2,3

¹Department of Radiology, University of California, San Diego, La Jolla, California 92093, United States.

Bioconjugate Chemistry

|August 24, 2023

Summary

This summary is machine-generated.

Researchers engineered plant virus nanoparticles to improve drug delivery. Mutants showed significantly increased reactivity and loading capacity for therapeutics and imaging agents, enhancing precision medicine applications.

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Area of Science:

Biotechnology
Nanomedicine
Drug Delivery Systems

Background:

Precision medicine requires efficient therapeutic delivery to target tissues.
Nanoparticle delivery systems offer improved pharmacokinetics and targeting over traditional methods.
Physalis mottle virus (PhMV)-like nanoparticles are a promising nanocarrier platform.

Purpose of the Study:

To engineer PhMV virus-like particles (VLPs) with enhanced internal loading capacity.
To increase the reactivity of PhMV VLPs towards thiol-reactive small molecules for cargo loading.
To improve PhMV VLPs for targeted delivery of therapeutics and imaging agents.

Main Methods:

Structure-based design was used to engineer cysteine-added mutants of PhMV VLPs.
Reactivity of mutants towards thiol-reactive small molecules was measured.
Internal loading capacity of engineered PhMV VLPs was assessed using chemotherapeutics and an MRI imaging reagent.

Main Results:

Engineered A31C and S137C mutants showed over 10-fold increased reactivity.
PhMV Cys1, Cys2, and double mutant VLPs exhibited up to 3-fold increased loading of chemotherapeutics (aldoxorubicin, vcMMAE).
Engineered VLPs showed up to 4-fold increased loading of the MRI imaging reagent DOTA(Gd).

Conclusions:

Engineered PhMV VLPs demonstrate significantly enhanced reactivity and internal loading capacity.
These improved nanocarriers show potential for advanced targeted delivery of drugs and imaging agents.
This work advances plant virus-based nanocarriers for in vivo precision medicine applications.