최한곤
2019-12-11T02:36:49Z
2019-12-11T02:36:49Z
2019-12
JOURNAL OF CONTROLLED RELEASE, v. 315, Page. 126-138
0168-3659
https://www.sciencedirect.com/science/article/pii/S016836591930611X
https://repository.hanyang.ac.kr/handle/20.500.11754/121221
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.
This research was supported by a grant from the National Research Foundation of Korea (NRF), funded by the Korea government (MSIP) (No. 2018R1A2A2A05021143), and by the Medical Research Center Program (2015R1A5A2009124) through the NRF funded by MSIP.
en_US
ELSEVIER SCIENCE BV
Doxorubicin
microRNA
Folic acid
Nanoparticle
PD-L1
Reprogramming the T cell response to cancer by simultaneous, nanoparticlemediated PD-L1 inhibition and immunogenic cell death
Article
315
10.1016/j.jconrel.2019.10.047
126-138
JOURNAL OF CONTROLLED RELEASE
Dai Phung, C.,
Nguyen, H.T.
Choi, J.Y.
Pham, T.T.
Acharya, S.
Timilshina, M.
Chang, J.H.
Kim, J.H.
Jeong, J.H.
Ku, S.K.
Choi, H.G.
Yong, C.S.
Kim, J.O
2019002890
E
COLLEGE OF PHARMACY[E]
DEPARTMENT OF PHARMACY
hangon