Issue 12, 2023

Sequential administration of virus-like particle-based nanomedicine to elicit enhanced tumor chemotherapy

Abstract

Protein cages have played a long-standing role in biomedicine applications, especially in tumor chemotherapy. Among protein cages, virus like particles (VLPs) have received attention for their potential applications in vaccine development and targeted drug delivery. However, most of the existing protein-based platform technologies are plagued with immunological problems that may limit their systemic delivery efficiency as drug carriers. Here, we show that using immune-orthogonal protein cages sequentially and modifying the dominant loop epitope can circumvent adaptive immune responses and enable effective drug delivery using repeated dosing. We genetically modified three different hepadnavirus core protein derived VLPs as delivery vectors for doxorubicin (DOX). These engineered VLPs have similar assembly characteristics, particle sizes, and immunological properties. Our results indicated that there was negligible antibody cross-reactivity in either direction between these three RGD-VLPs in mice that were previously immunized against HBc VLPs. Moreover, the sequential administration of multiple RGD-VLP-based nanomedicine (DOX@RGD-VLPs) could effectively reduce immune clearance and inhibited tumor growth. Hence, this study could provide an attractive protein cage-based platform for therapeutic drug delivery.

Graphical abstract: Sequential administration of virus-like particle-based nanomedicine to elicit enhanced tumor chemotherapy

Supplementary files

Article information

Article type
Paper
Submitted
11 oct. 2022
Accepted
20 dic. 2022
First published
21 dic. 2022

J. Mater. Chem. B, 2023,11, 2674-2683

Sequential administration of virus-like particle-based nanomedicine to elicit enhanced tumor chemotherapy

C. Wang, C. Xiao, Y. Chen, Y. Li, Q. Zhang, W. Shan, Y. Li, S. Bi, Y. Wang, X. Wang and L. Ren, J. Mater. Chem. B, 2023, 11, 2674 DOI: 10.1039/D2TB02163C

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