Self-assembled star-shaped chlorin-core poly(epsilon-caprolactone)-poly(ethylene glycol) diblock copolymer micelles for dual chemo-photodynamic therapies.
Amphiphilic 4-armed star-shaped chlorin-core diblock copolymers based on methoxy poly(ethylene glycol) (mPEG) and poly (epsilon-caprolactone) (PCL) were synthesized and characterized in this study. The synthesized photosensitizer-centered amphiphilic star block copolymer that forms assembled micelle-like structures can be used in a photodynamic therapy (PDT)-functionalized drug delivery system. Moreover, the hydrophobic chemotherapeutic agent, paclitaxel, can be trapped in the hydrophobic inner core of micelles. In our results, the star-polymer-formed micelle exhibited efficient singlet oxygen generation, whereas the hydrophobic photosensitizer failed due to aggregation in aqueous solution. The chlorin-core micelle without paclitaxel loading exhibited obvious phototoxicity in MCF-7 breast cancer cells with 7J/cm2 or 14J/cm2 light irradiation at a chlorin concentration of 125microg/ml. After paclitaxel loading, the size of micelle increased from 71.4nm to 103.2nm. Surprisingly, these micelles were found to improve the cytotoxicity of paclitaxel significantly in MCF-7 cells after irradiation through a synergistic effect evaluated by median effect analysis. This functionalized micellar delivery system is a potential dual carrier for the synergistic combination of photodynamic therapy and chemotherapy for the treatment of cancer.
Peng
Cheng-Liang
CL
Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei 100, Taiwan.
Shieh
Ming-Jium
MJ
Tsai
Ming-Hsien
MH
Chang
Cheng-Chung
CC
Lai
Ping-Shan
PS
D001672:Biocompatible Materials / Q000737:chemistry / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry*; D004358:Drug Therapy / Q000379:methods*; D005026:Ethylene Glycols / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D008823:Micelles; D008870:Microtubules / Q000378:metabolism; D015394:Molecular Structure; D017239:Paclitaxel / Q000378:metabolism; D010778:Photochemotherapy / Q000379:methods*; D011091:Polyesters / Q000737:chemistry / Q000627:therapeutic use; D011108:Polymers / Q000737:chemistry / Q000627:therapeutic use; D011166:Porphyrins / Q000737:chemistry / Q000627:therapeutic use; D026082:Singlet Oxygen / Q000737:chemistry / Q000378:metabolism; D050257:Tubulin Modulators / Q000378:metabolism
D001672:Biocompatible Materials; D004337:Drug Carriers; D005026:Ethylene Glycols; D008823:Micelles; D011091:Polyesters; D011108:Polymers; D011166:Porphyrins; D050257:Tubulin Modulators; C476300:poly(epsilon-caprolactone)-b-poly(ethylene glycol); D026082:Singlet Oxygen; C006969:chlorin; D017239:Paclitaxel