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Reprogramming the T cell response to cancer by simultaneous, nanoparticlemediated PD-L1 inhibition and immunogenic cell death

Title
Reprogramming the T cell response to cancer by simultaneous, nanoparticlemediated PD-L1 inhibition and immunogenic cell death
Author
최한곤
Keywords
Doxorubicin; microRNA; Folic acid; Nanoparticle; PD-L1
Issue Date
2019-12
Publisher
ELSEVIER SCIENCE BV
Citation
JOURNAL OF CONTROLLED RELEASE, v. 315, Page. 126-138
Abstract
In this study, dual drug-loaded nanoparticles were constructed to co-deliver low-dose doxorubicin (DOX) and miR-200c (DOX/miR-NPs) to inhibit programmed death-1 receptor (PD-L1) expression and trigger immunogenic cell death (ICD) in cancer cells. Two block copolymers, folic acid (FA)-conjugated PLGA-PEG (PLGA-PEG-FA) and PLGA-PEI, were formulated as folate-targeted NPs and loaded with DOX and miR-200c. The NPs, which were formed as nanosize objects (110.4 ± 2.1) with narrow size distribution (0.19 ± 0.02), effectively protected the miR-200c from degradation in serum. Modifying the NPs with FA increased not only their uptake by cancer cells in vitro but also their accumulation in tumor microenvironments in vivo, as compared with those properties of non-FA-modified NPs. The DOX/miR-NPs also exhibited efficacious inhibition of PD-L1 expression and robust induction of ICD in cancer cells in vitro and in vivo, resulting in increased dendritic cell maturation and CD8+ T cell response towards cancer cells. Furthermore, tumor growth was significantly inhibited by folate-targeted NPs loaded with the low-dose DOX/miR-200c combination, but not by treatments with free DOX, miR-NPs or DOX-NPs. Thus, our results suggest that simultaneous PD-L1 inhibition via microRNAs and the induction of an immunogenic tumor microenvironment via low-dose cytotoxic drugs may improve cancer therapy efficacy.
URI
https://www.sciencedirect.com/science/article/pii/S016836591930611Xhttps://repository.hanyang.ac.kr/handle/20.500.11754/121221
ISSN
0168-3659
DOI
10.1016/j.jconrel.2019.10.047
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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