Graft and diblock copolymer multifunctional micelles for cancer chemotherapy and imaging

Hsieh Chih Tsai; Wei Hsiang Chang; Chun Liang Lo; Cheng Hung Tsai; Che Hau Chang; Ta Wei Ou; Tzu Chen Yen; Ging Ho Hsiue

doi:10.1016/j.biomaterials.2009.11.059

Graft and diblock copolymer multifunctional micelles for cancer chemotherapy and imaging

Hsieh Chih Tsai, Wei Hsiang Chang, Chun Liang Lo, Cheng Hung Tsai, Che Hau Chang, Ta Wei Ou, Tzu Chen Yen, Ging Ho Hsiue^*

^*Corresponding author for this work

Department of Biomedical Engineering

Research output: Contribution to journal › Article › peer-review

102 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	2293-2301
Number of pages	9
Journal	Biomaterials
Volume	31
Issue number	8
DOIs	https://doi.org/10.1016/j.biomaterials.2009.11.059
State	Published - Mar 2010

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title = "Graft and diblock copolymer multifunctional micelles for cancer chemotherapy and imaging",

abstract = "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.",

author = "Tsai, {Hsieh Chih} and Chang, {Wei Hsiang} and Lo, {Chun Liang} and Tsai, {Cheng Hung} and Chang, {Che Hau} and Ou, {Ta Wei} and Yen, {Tzu Chen} and Hsiue, {Ging Ho}",

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AU - Tsai, Hsieh Chih

AU - Chang, Wei Hsiang

AU - Lo, Chun Liang

AU - Tsai, Cheng Hung

AU - Chang, Che Hau

AU - Ou, Ta Wei

AU - Yen, Tzu Chen

AU - Hsiue, Ging Ho

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AB - 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.

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Graft and diblock copolymer multifunctional micelles for cancer chemotherapy and imaging

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