title: 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.
abstract: 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 (P71 D3 )-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 (P296 D1 ) vesicles. DOX released from the resultant P71 D3 /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 P71 D3 /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.
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
authors.forename: Geetha
authors.initials: G
authors.lastname: Viswanathan
authors.affiliation: Department of Chemical Engineering, National Taiwan University of Science and Technology, 43 Section 4, Keelung Road, Taipei, 10607, Taiwan.
authors.forename: Yu-Hsuan
authors.initials: YH
authors.lastname: Hsu
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
authors.forename: Siew Hui
authors.initials: SH
authors.lastname: Voon
authors.affiliation: Department of Chemical Engineering, National Taiwan University of Science and Technology, 43 Section 4, Keelung Road, Taipei, 10607, Taiwan.|Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, 43 Section 4, Keelung Road, Taipei, 10607, Taiwan.
authors.forename: Toyoko
authors.initials: T
authors.lastname: Imae
authors.affiliation: Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, 43 Section 4, Keelung Road, Taipei, 10607, Taiwan.
authors.forename: Ampornphan
authors.initials: A
authors.lastname: Siriviriyanun
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
authors.forename: Hong Boon
authors.initials: HB
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
authors.forename: Lik Voon
authors.initials: LV
authors.lastname: Kiew
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
authors.forename: Lip Yong
authors.initials: LY
authors.lastname: Chung
authors.affiliation: Department of Materials Science and Chemistry, University of Hyogo, 2167 Shosha, Himeji, Hyogo, 671-2280, Japan.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Yusa
mesh_terms: D000873:Anthracenes / Q000008:administration & dosage / Q000737:chemistry; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D050091:Dendrimers / Q000008:administration & dosage / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D005260:Female; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage*; D013501:Surface-Active Agents / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000873:Anthracenes; D000970:Antineoplastic Agents; D050091:Dendrimers; D004337:Drug Carriers; D011108:Polymers; D013501:Surface-Active Agents; C501244:dendron; D004317:Doxorubicin
keywords: cellular uptake; diblock copolymer micelles; pendant dendron; self-assemblies; subcellular localization