Doxorubicin-loaded plga nanoparticles for cancer therapy: Molecular weight effect of plga in doxorubicin release for controlling immunogenic cell death

Yongwhan Choi, Hong Yeol Yoon, Jeongrae Kim, Suah Yang, Jaewan Lee, Ji Woong Choi, Yujeong Moon, Jinseong Kim, Seungho Lim, Man Kyu Shim, Sangmin Jeon, Ick Chan Kwon, Kwangmeyung Kim

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number1165
Pages (from-to)1-18
Number of pages18
JournalPharmaceutics
Volume12
Issue number12
DOIs
Publication statusPublished - 2020

Keywords

  • Cancer immunotherapy
  • Drug release
  • Immunogenic cell death
  • Nanomedicine

ASJC Scopus subject areas

  • Pharmaceutical Science

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