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Tumor microenvironment-responsive and oxygen self-sufficient oil droplet nanoparticles for enhanced photothermal/photodynamic combination therapy against hypoxic tumors.

Abstract
The combination of photothermal and photodynamic therapy (PTT/PDT) shows pronounced potential as a prominent therapeutic strategy for tumor treatment. However, the efficacy is limited by insufficient tumor-targeted delivery of PTT and PDT reagents and the hypoxic nature of the tumor microenvironment. To overcome these limitations, tumor acidity-responsive lipid membrane-enclosed perfluorooctyl bromide oil droplet nanoparticles (NPs) surface modified with N-acetyl histidine-modified D-α-tocopheryl polyethylene glycol 1000 succinate (PFOB@IMHNPs) were developed, capable of co-delivering oxygen, IR780 (a photothermal agent) and mTHPC (a photodynamic sensitizer) into tumors. Through self-sufficient oxygen transportation in combination with promotion of cellular uptake upon acid-triggered generation of surface positive charge, the PFOB@IMHNPs effectively delivered IR780 and mTHPC and produced singlet oxygen within hypoxic TRAMP-C1 cells following exposure to irradiation at 660 nm. This led to effective killing of hypoxic cancer cells in vitro. Importantly, when irradiation at 808 and 660 nm was carried out, PT/PD combination therapy utilizing PFOB@IMHNPs dramatically suppressed the growth of TRAMP-C1 tumors through effective tumor-targeted cargo delivery and relief of tumor hypoxia. Our results suggest the high potential of the PFOB@IMHNPs developed in this study in clinical application for cancer treatment.
AuthorsReesha Kv, Te-I Liu, I-Lin Lu, Chia-Chen Liu, Hsin-Hung Chen, Ting-Yu Lu, Wen-Hsuan Chiang, Hsin-Cheng Chiu
JournalJournal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 328 Pg. 87-99 (12 10 2020) ISSN: 1873-4995 [Electronic] Netherlands
PMID32858076 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2020 Elsevier B.V. All rights reserved.
Chemical References
  • Photosensitizing Agents
  • Oxygen
Topics
  • Cell Line, Tumor
  • Humans
  • Nanoparticles
  • Neoplasms (drug therapy)
  • Oxygen
  • Photochemotherapy
  • Photosensitizing Agents (therapeutic use)
  • Tumor Microenvironment

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