2. Academic Validation
  3. Physalis Mottle Virus-Like Nanocarriers with Expanded Internal Loading Capacity

Physalis Mottle Virus-Like Nanocarriers with Expanded Internal Loading Capacity

  • Bioconjug Chem. 2023 Aug 24. doi: 10.1021/acs.bioconjchem.3c00269.
Krister J Barkovich 1,  Zhuohong Wu 2 3,  Zhongchao Zhao 2 3,  Andrea Simms 2 3,  Eric Y Chang 1 4,  Nicole F Steinmetz 1 2 3 5 6 7 8 9
Affiliations

Affiliations

  • 1 Department of Radiology, University of California, San Diego, La Jolla, California 92093, United States.
  • 2 Department of NanoEngineering, University of California, San Diego, La Jolla, California 92093, United States.
  • 3 Center for Nano-ImmunoEngineering, University of California, San Diego, La Jolla, California 92093, United States.
  • 4 Radiology Service, VA San Diego Healthcare System, San Diego, La Jolla, California 92093, United States.
  • 5 Department of Bioengineering, University of California, San Diego, La Jolla, California 92093, United States.
  • 6 Institute for Materials Discovery and Design, University of California, La Jolla, California 92093, United States.
  • 7 Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, United States.
  • 8 Center for Engineering in Cancer, Institute for Engineering in Medicine, University of California, San Diego, La Jolla, California 92093, United States.
  • 9 Shu and K.C. Chien and Peter Farrell Collaboratory, University of California, San Diego, La Jolla, California 92093, United States.
PMID: 37615599 DOI: 10.1021/acs.bioconjchem.3c00269
Abstract

An ongoing challenge in precision medicine is the efficient delivery of therapeutics to tissues/organs of interest. Nanoparticle delivery systems have the potential to overcome traditional limitations of drug and gene delivery through improved pharmacokinetics, tissue targeting, and stability of encapsulated cargo. Physalis mottle virus (PhMV)-like nanoparticles are a promising nanocarrier platform which can be chemically targeted on the exterior and interior surfaces through reactive Amino acids. Cargo-loading to the internal cavity is achieved with thiol-reactive small molecules. However, the internal loading capacity of these nanoparticles is limited by the presence of a single reactive cysteine (C75) per coat protein with low inherent reactivity. Here, we use structure-based design to engineer cysteine-added mutants of PhMV VLPs that display increased reactivity toward thiol-reactive small molecules. Specifically, the A31C and S137C mutants show a greater than 10-fold increased rate of reactivity towards thiol-reactive small molecules, and PhMV Cys1 (A31C), PhMV Cys2 (S137C), and PhMV Cys1+2 (double mutant) VLPs display up to three-fold increased internal loading of the small molecule chemotherapeutics aldoxorubicin and vcMMAE and up to four-fold increased internal loading of the MRI imaging reagent DOTA(Gd). These results further improve upon a promising plant virus-based nanocarrier system for use in targeted delivery of small-molecule drugs and imaging reagents in vivo.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z