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Biomimetic polymeric nanoparticle-based photodynamic immuno-therapy against primary and distant tumors

Abstract

In this study, we aimed to design a bionanomaterial that could exert anticancer effects against primary and distant tumors via photodynamic immunotherapy. As a biomaterial, we used an amphiphilic phenylalanine derivative of poly gamma glutamic acid, which forms nanoparticles (AN) by self-assembly. For anticancer effects, we co-entrapped hydrophobic chlorin e6 and monophosphoryl lipid A in the core of the AN, to generate M/C/AN. For comparison, we used plain AN and chlorin e6-loaded AN (C/AN). In vitro studies showed that B16F10 cancer cells treated with C/AN or M/C/AN generated reactive oxygen species and exhibited enhanced surface display of calreticulin upon exposure to 660-nm light irradiation. C/AN and M/C/AN exerted similar photodynamic anticancer effects; however, M/C/AN, but not C/AN, induced in vitro dendritic cell maturation. Our biodistribution study revealed that C/AN and M/C/AN showed higher accumulation at the tumor tissues compared to that seen in the free chlorin e6-treated group. In B16F10 tumor-bearing mice, the intravenous injection of C/AN or M/C/AN showed similar photodynamic anticancer effects against primary tumors. However, the growth of distant tumors was more significantly inhibited in the M/C/AN group compared to the C/AN group. At day 40 after inoculation of the primary tumor, MC/AN-treated mice showed 100% survival, whereas the other groups showed 0% survival. In the tumor microenvironment, higher infiltration of CD8 T cells was observed in the M/C/AN group compared to the other groups. Our results suggest that AN co-loaded with a photosensitizer and an immune stimulant may hold great potential to confer photodynamic immunotherapy to inhibit both primary and distant tumors.

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Article information


Submitted
23 Oct 2019
Accepted
09 Jan 2020
First published
10 Jan 2020

Biomater. Sci., 2020, Accepted Manuscript
Article type
Paper

Biomimetic polymeric nanoparticle-based photodynamic immuno-therapy against primary and distant tumors

D. Kim, J. Byun, J. Park, Y. Lee, G. Shim and Y. Oh, Biomater. Sci., 2020, Accepted Manuscript , DOI: 10.1039/C9BM01704F

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