Graft and diblock copolymer multifunctional micelles for cancer chemotherapy and imaging.
Multifunctional mixed micelles that constructed from poly(HEMA-co-histidine)-g-PLA and diblock copolymer PEG-PLA with functional moiety was developed in this study. The mixed micelles had well defined core shell structure which was evaluated by TEM. The functional inner core of poly(HEMA-co-histidine)-g-PLA exhibited pH stimulate to enable intracellular drug delivery and outer shell of PEG-b-PLA with functional moiety Cy5.5 for biodistribution diagnosis and folate for cancer specific targeting were synthesized at the end of the polymer chain. The graft and diblock copolymer self assembled to nanospheres against water with an average diameter below 120 nm without doxorubicin, and an average diameter of around 200 nm when loaded with drug. From drug released study, a change in pH destroy the inner core to lead a significant doxorubicin(Dox) release from mixed micelles. Cellular uptake of folate-micelles was found to be higher than that of non-folate-micelles due to the folate-binding effect on the cell membrane, thereby providing a similar cytotoxic effect to drug only against the HeLa cell line. In vivo study revealed that specific targeting of folate-micelles exhibited cancer targeting and efficiency expression on tumor growth, indicating that multifunctional micelles prepared from poly(HEA-co-histidine)-g-PLA and folate-PEG-PLA have great potential in cancer chemotherapy and diagnosis.
Tsai
Hsieh-Chih
HC
Department of Chemical Engineering, National Tsing Hua University, Hsinchu, 300 Taiwan, ROC.
Chang
Wei-Hsiang
WH
Lo
Chun-Liang
CL
Tsai
Cheng-Hung
CH
Chang
Che-Hau
CH
Ou
Ta-Wei
TW
Yen
Tzu-Chen
TC
Hsiue
Ging-Ho
GH
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000627:therapeutic use; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D004317:Doxorubicin / Q000737:chemistry / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D016503:Drug Delivery Systems; D005492:Folic Acid / Q000737:chemistry / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008823:Micelles; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy*; D011108:Polymers / Q000737:chemistry / Q000627:therapeutic use; D014018:Tissue Distribution
D000903:Antibiotics, Antineoplastic; D001672:Biocompatible Materials; D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D004317:Doxorubicin; D005492:Folic Acid