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Article

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

1
KU-KIST Graduate School of Converging Science and Technology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea
2
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea
*
Authors to whom correspondence should be addressed.
Pharmaceutics 2020, 12(12), 1165; https://doi.org/10.3390/pharmaceutics12121165
Received: 16 September 2020 / Revised: 26 November 2020 / Accepted: 27 November 2020 / Published: 29 November 2020
(This article belongs to the Special Issue Controlled Release of Nanostructured Drug Systems)
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-PLGA7K NPs showed faster DOX release kinetics than DOX-PLGA12K NPs in the physiological condition. DOX-PLGA7K NPs and DOX-PLGA12K 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-PLGA7K NPs and DOX-PLGA12K 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. View Full-Text
Keywords: cancer immunotherapy; immunogenic cell death; nanomedicine; drug release cancer immunotherapy; immunogenic cell death; nanomedicine; drug release
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MDPI and ACS Style

Choi, Y.; Yoon, H.Y.; Kim, J.; Yang, S.; Lee, J.; Choi, J.W.; Moon, Y.; Kim, J.; Lim, S.; Shim, M.K.; Jeon, S.; Kwon, I.C.; Kim, K. Doxorubicin-Loaded PLGA Nanoparticles for Cancer Therapy: Molecular Weight Effect of PLGA in Doxorubicin Release for Controlling Immunogenic Cell Death. Pharmaceutics 2020, 12, 1165. https://doi.org/10.3390/pharmaceutics12121165

AMA Style

Choi Y, Yoon HY, Kim J, Yang S, Lee J, Choi JW, Moon Y, Kim J, Lim S, Shim MK, Jeon S, Kwon IC, Kim K. Doxorubicin-Loaded PLGA Nanoparticles for Cancer Therapy: Molecular Weight Effect of PLGA in Doxorubicin Release for Controlling Immunogenic Cell Death. Pharmaceutics. 2020; 12(12):1165. https://doi.org/10.3390/pharmaceutics12121165

Chicago/Turabian Style

Choi, Yongwhan, Hong Y. Yoon, Jeongrae Kim, Suah Yang, Jaewan Lee, Ji W. Choi, Yujeong Moon, Jinseong Kim, Seungho Lim, Man K. Shim, Sangmin Jeon, Ick C. Kwon, and Kwangmeyung Kim. 2020. "Doxorubicin-Loaded PLGA Nanoparticles for Cancer Therapy: Molecular Weight Effect of PLGA in Doxorubicin Release for Controlling Immunogenic Cell Death" Pharmaceutics 12, no. 12: 1165. https://doi.org/10.3390/pharmaceutics12121165

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