Doxorubicin-Loaded PLGA Nanoparticles for Cancer Therapy: Molecular Weight Effect of PLGA in Doxorubicin Release for Controlling Immunogenic Cell Death

Pharmaceutics

Yujeong Moon¹  Hong Yeol Yoon¹  Sangmin Jeon¹  Man Kyu Shim¹  Seungho Lim¹  Jiwoong Choi²  Jaewan Lee²  Suah Yang²  Jeongrae Kim²  Yongwhan Choi²  Kwangmeyung Kim²  Ick Chan Kwon²  Jinseong Kim² 

[1] Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea;KU-KIST Graduate School of Converging Science and Technology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea;

关键词: cancer immunotherapy;    immunogenic cell death;    nanomedicine;    drug release;   

DOI  :  10.3390/pharmaceutics12121165

来源: DOAJ

【 摘 要 】

Direct local delivery of immunogenic cell death (ICD) inducers to a tumor site is an attractive approach for leading ICD effectively, due to enabling the concentrated delivery of ICD inducers to the tumor site. Herein, we prepared doxorubicin (DOX)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) using different molecular weight PLGA (7000 g/mol and 12,000 g/mol), showing different drug release kinetics. The different release kinetics of DOX might differently stimulate a tumor cell-specific immune response by releasing damage-associated molecular patterns (DAMPs), resulting in showing a different antitumor response in the living body. DOX-PLGA_7K NPs showed faster DOX release kinetics than DOX-PLGA_12K NPs in the physiological condition. DOX-PLGA_7K NPs and DOX-PLGA_12K NPs were successfully taken up by the CT-26 tumor cells, subsequently showing different DOX localization times at the nucleus. Released DOX successfully lead to cytotoxicity and HMGB1 release in vitro. Although the DOX-PLGA_7K NPs and DOX-PLGA_12K NPs showed different sustained DOX release kinetics in vitro, tumor growth of the CT-26 tumor was similarly inhibited for 28 days post-direct tumor injection. Furthermore, the immunological memory effect was successfully established by the ICD-based tumor-specific immune responses, including DC maturation and tumor infiltration of cytotoxic T lymphocytes (CTLs). We expect that the controlled release of ICD-inducible chemotherapeutic agents, using different types of nanomedicines, can provide potential in precision cancer immunotherapy by controlling the tumor-specific immune responses, thus improving the therapeutic efficacy.

【 授权许可】

Unknown