Active Microneedle Administration of Plant Virus Nanoparticles for Cancer In Situ Vaccination Improves Immunotherapeutic Efficacy
- 7 August 2020
- journal article
- research article
- Published by American Chemical Society (ACS) in ACS Applied Nano Materials
- Vol. 3 (8), 8037-8051
- https://doi.org/10.1021/acsanm.0c01506
Abstract
The solid tumor microenvironment (TME) poses a significant structural and biochemical barrier to immunotherapeutic agents. To address the limitations of tumor penetration and distribution and to enhance antitumor efficacy of immunotherapeutics, we present here an autonomous active microneedle (MN) system for the direct intratumoral (IT) delivery of a potent immunoadjuvant, cowpea mosaic virus nanoparticles (CPMV), in vivo. In this active delivery system, magnesium (Mg) microparticles embedded into active MNs react with the interstitial fluid in the TME, generating a propulsive force to drive the nanoparticle payload into the tumor. Active delivery of the CPMV payload into B16F10 melanomas in vivo demonstrated substantially more pronounced tumor regression and prolonged survival of tumor-bearing mice compared to that of passive MNs and conventional needle injection. Active MN administration of CPMV also enhanced local innate and systemic adaptive antitumor immunity. Our approach represents an elaboration of conventional CPMV in situ vaccination, highlighting substantial immune-mediated antitumor effects and improved therapeutic efficacy that can be achieved through CPMV in situ vaccination mediated by an active and autonomous delivery system.Funding Information
- National Cancer Institute (U01CA218292)
- Society of Interventional Radiology Foundation
- Consejo Nacional de Ciencia y Tecnolog?a
- University of California Institute for Mexico and the United States
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