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.
Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei 100, Taiwan.
Cheng-Liang
CL
Peng
Ming-Jium
MJ
Shieh
Ming-Hsien
MH
Tsai
Cheng-Chung
CC
Chang
Ping-Shan
PS
Lai
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