Photoactivation switch from type II to type i reactions by electron-rich micelles for improved photodynamic therapy of cancer cells under hypoxia

Huiying Ding, Haijun Yu, Ying Dong, Ruhai Tian, Gang Huang, David A. Boothman, Baran D. Sumer, Jinming Gao

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Photodynamic therapy (PDT) is an emerging clinical modality for the treatment of a variety of diseases. Most photosensitizers are hydrophobic and poorly soluble in water. Many new nanoplatforms have been successfully established to improve the delivery efficiency of PS drugs. However, few reported studies have investigated how the carrier microenvironment may affect the photophysical properties of photosensitizer (PS) drugs and subsequently, their biological efficacy in killing malignant cells. In this study, we describe the modulation of type I and II photoactivation processes of the photosensitizer, 5,10,15,20-tetrakis(meso-hydroxyphenyl)porphyrin (mTHPP), by the micelle core environment. Electron-rich poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) micelles increased photoactivations from type II to type I mechanisms, which significantly increased the generation of O 2 - through the electron transfer pathway over 1O 2 production through energy transfer process. The PDPA micelles led to enhanced phototoxicity over the electron-deficient poly(d,l-lactide) control in multiple cancer cell lines under argon-saturated conditions. These data suggest that micelle carriers may not only improve the bioavailability of photosensitizer drugs, but also modulate photophysical properties for improved PDT efficacy.

Original languageEnglish (US)
Pages (from-to)276-280
Number of pages5
JournalJournal of Controlled Release
Volume156
Issue number3
DOIs
StatePublished - Dec 20 2011

Fingerprint

Cell Hypoxia
Photosensitizing Agents
Photochemotherapy
Micelles
Electrons
Neoplasms
Pharmaceutical Preparations
Phototoxic Dermatitis
Argon
Energy Transfer
Porphyrins
Biological Availability
Cell Line
Water

Keywords

  • Nanoparticle delivery
  • Photodynamic therapy
  • Photoinduced electron transfer
  • Polymeric micelles
  • Reactive oxygen species

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

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abstract = "Photodynamic therapy (PDT) is an emerging clinical modality for the treatment of a variety of diseases. Most photosensitizers are hydrophobic and poorly soluble in water. Many new nanoplatforms have been successfully established to improve the delivery efficiency of PS drugs. However, few reported studies have investigated how the carrier microenvironment may affect the photophysical properties of photosensitizer (PS) drugs and subsequently, their biological efficacy in killing malignant cells. In this study, we describe the modulation of type I and II photoactivation processes of the photosensitizer, 5,10,15,20-tetrakis(meso-hydroxyphenyl)porphyrin (mTHPP), by the micelle core environment. Electron-rich poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) micelles increased photoactivations from type II to type I mechanisms, which significantly increased the generation of O 2 - through the electron transfer pathway over 1O 2 production through energy transfer process. The PDPA micelles led to enhanced phototoxicity over the electron-deficient poly(d,l-lactide) control in multiple cancer cell lines under argon-saturated conditions. These data suggest that micelle carriers may not only improve the bioavailability of photosensitizer drugs, but also modulate photophysical properties for improved PDT efficacy.",
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AU - Yu, Haijun

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AU - Tian, Ruhai

AU - Huang, Gang

AU - Boothman, David A.

AU - Sumer, Baran D.

AU - Gao, Jinming

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