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J. Control. Release, Vol 359, July 2023, Pages 52-68 | http://doi.org/10.1016/j.jconrel.2023.05.025 Development and characterization of pH-responsive nanocarriers for chemo-photothermal combination therapy of acidic tumors

Patihul Husni ^a,b, Yuseon Shin ^a,b, Hyewon Jeon ^a,b, Eun Seong Lee ^c, Yu Seok Youn ^d, Chi-Duen Poon ^e, Chaemin Lim ^a,b, Kyung Taek Oh ^a,b

^aDepartment of Global Innovative Drugs, The Graduate School of Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul 06974, Republic of Korea
^bCollege of Pharmacy, Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul 06974, Republic of Korea
^cDepartment of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Bucheon-si 14662, Gyeonggi-do, Republic of Korea
^dSchool of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon 16419, Gyeonggi-do, Republic of Korea
^eResearch Computer Center, University of North Carolina Chapel Hill, Chapel Hill, NC 27599, USA

Corresponding authors : Chaemin Lim, Kyung Taek Oh

Abstract

The combination of photothermal therapy and chemotherapy has been considered a promising strategy for improving the excellent antitumor activities of these treatments. In this study, we developed a new simple type of pH-sensitive chemo-photothermal combination agent capable of repeated exposures to a near-infrared (NIR) laser and evaluated its anticancer efficacy in vitro and in vivo. Doxorubicin (Dox) and gold nanoclusters (GNCs) were successfully co-loaded into pH-sensitive nanoparticles (poly(ethylene glycol)-poly[(benzyl-l-aspartate)-co-(N-(3-aminopropyl)imidazole-L-aspartamide)] (PEG-PABI)), resulting in a particle size of approximately120 nm with a narrow size distribution. The dual drug-loaded nanoparticles (Dox/GNC-loaded PEG-PABI micelles (Dox/GNC-Ms)) showed consistent pH-sensitive properties and heat generation efficiency after repeated NIR laser exposure. In particular, GNC-M has improved photothermal stability while maintaining high photothermal conversion efficiency, addressing the shortcomings of previous gold nanoparticles. As the concentration of GNC-Ms, irradiation light exposure time, and light source intensity increased, the amount of heat generated and the anticancer effect increased. When Dox was encapsulated with GNCs (Dox/GNC-Ms), a faster drug release rate under acidic pH conditions and a strong synergistic effect against U87MG cells were observed. When the Dox/GNC-M system was extended to in vivo studies, it effectively increased the temperature of the tumor tissue under near-infrared irradiation and showed excellent anticancer efficacy. Therefore, the Dox/GNC-M system could be a simple but promising strategy for chemo-photothermal combination treatment capable of targeting acidic tumors.

논문정보

형식Research article
게재일2023년 07월 (BRIC 등록일 2023-06-23)
연구진국내 연구진
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