Concept paperPhotoactivation switch from type II to type I reactions by electron-rich micelles for improved photodynamic therapy of cancer cells under hypoxia
Graphical abstract
Table of Content Graphics: The electron-rich mTHPP-PDPA micelles resulted in the increase of type I photoactivation reactions and higher phototoxicity in multiple cancer cells under hypoxic conditions.
Section snippets
Concept and hypothesis
Photodynamic therapy (PDT) is an emerging clinical modality that has received considerable attention for the treatment of cancer, cardiovascular, dermatological, and ophthalmic diseases [1], [2], [3]. PDT has three essential elements: a photosensitizer (PS), light and oxygen. New photosensitizing drugs based on porphyrins and chemically related compounds such as chlorins and phthalocyanines have been under extensive investigations [4], [5]. Most photosensitizers are hydrophobic and poorly
Preparation of mTHPP-loaded micelles
PEG-b-PDPA and PEG-b-PLA copolymers were synthesized using atom transfer radical polymerization (ATRP) [23] and ring-opening polymerization [24] methods, respectively. The PEG segments in both copolymers were controlled at 5 kD. The PDPA and PLA segments were controlled at 10 kD. mTHPP-loaded PEG-b-PLA (mTHPP-PLA) and PEG-b-PDPA (mTHPP-PDPA) micelles were produced using a solvent evaporation method [25]. Briefly, a proper amount of the copolymer was first dissolved in tetrahydrofuran (THF) with
Conclusions
In summary, we report the development of a novel PS nanoparticle formulation that confers greater PDT cytotoxicity against cancer cells under hypoxic conditions. The photophysical and photodynamic properties of mTHPP are highly dependent on the micelle core environment. With the electron-donating PDPA segment, the generation of O2− through the electron transfer pathway competes with 1O2 production through the energy transfer process under aerobic environments, and becomes dominant under hypoxic
Acknowledgement
This research is supported by the National Cancer Institute to JG (R01CA122994 and R01CA129011) and to DAB (R01CA102792) and the National Center for Research Resources to BDS (5 UL1 RR024982-02). This is manuscript CSCN060 from the Program of Cell Stress and Cancer Nanomedicine in the Simmons Cancer Center. We thank Yanhong Liu at Technical Institute of Physics and Chemistry, CAS for assistance with ESR studies, Kejin Zhou for helpful discussions, and Vikram Kodibagkar and Praveen Gulaka for
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