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A Comparative Study of Cellular Uptake and Subcellular Localization of Doxorubicin Loaded in Self‐Assemblies of Amphiphilic Copolymers with Pendant Dendron by MDA‐MB‐231 Human Breast Cancer Cells
Author(s) -
Viswanathan Geetha,
Hsu YuHsuan,
Voon Siew Hui,
Imae Toyoko,
Siriviriyanun Ampornphan,
Lee Hong Boon,
Kiew Lik Voon,
Chung Lip Yong,
Yusa Shinichi
Publication year - 2016
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.201500435
Subject(s) - nanocarriers , micelle , doxorubicin , amphiphile , chemistry , biophysics , drug delivery , dendrimer , drug carrier , copolymer , cytotoxicity , drug , cancer cell , biochemistry , cancer , pharmacology , in vitro , organic chemistry , biology , chemotherapy , aqueous solution , genetics , polymer
Previously synthesized amphiphilic diblock copolymers with pendant dendron moieties have been investigated for their potential use as drug carriers to improve the delivery of an anticancer drug to human breast cancer cells. Diblock copolymer (P 71 D 3 )‐based micelles effectively encapsulate the doxorubicin (DOX) with a high drug‐loading capacity (≈95%, 104 DOX molecules per micelle), which is approximately double the amount of drug loaded into the diblock copolymer (P 296 D 1 ) vesicles. DOX released from the resultant P 71 D 3 /DOX micelles is approximately 1.3‐fold more abundant, at a tumoral acidic pH of 5.5 compared with a pH of 7.4. The P 71 D 3 /DOX micelles also enhance drug potency in breast cancer MDA‐MB‐231 cells due to their higher intracellular uptake, by approximately twofold, compared with the vesicular nanocarrier, and free DOX. Micellar nanocarriers are taken up by lysosomes via energy‐dependent processes, followed by the release of DOX into the cytoplasm and subsequent translocation into the nucleus, where it exert its cytotoxic effect.