Targeted co-delivery of polypyrrole and rapamycin by trastuzumab-conjugated liposomes for combined chemo-photothermal therapy

[Display omitted] Trastuzumab is a therapeutic monoclonal antibody that selectively recognizes HER2/neu receptor for targeting breast cancers. In this study, we aimed to present a strategy to combine chemo and phototherapy and targeted delivery via monoclonal antibody for enhanced anticancer effects...

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Bibliographic Details
Published in:International journal of pharmaceutics 2017-07, Vol.527 (1-2), p.61-71
Main Authors: Nguyen, Hanh Thuy, Tran, Tuan Hiep, Thapa, Raj Kumar, Phung, Cao Dai, Shin, Beom Soo, Jeong, Jee-Heon, Choi, Han-Gon, Yong, Chul Soon, Kim, Jong Oh
Format: Article
Language:English
Subjects:
Antibodies, Monoclonal, Humanized
Antineoplastic Agents - administration & dosage
Breast cancer
Breast Neoplasms - drug therapy
Cell Line, Tumor
Drug Carriers - chemistry
Humans
Liposomes - chemistry
Photochemotherapy
Polymers - administration & dosage
Polypyrrole
Pyrroles - administration & dosage
Rapamycin
Receptor, ErbB-2 - metabolism
Sirolimus - administration & dosage
Targeted nanoparticle
Trastuzumab
Trastuzumab - administration & dosage
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Summary:[Display omitted] Trastuzumab is a therapeutic monoclonal antibody that selectively recognizes HER2/neu receptor for targeting breast cancers. In this study, we aimed to present a strategy to combine chemo and phototherapy and targeted delivery via monoclonal antibody for enhanced anticancer effects. We co-loaded a chemotherapeutic agent, rapamycin, and a photosensitizer, polypyrrole, in trastuzumab-conjugated liposomes (LRPmAb) for combined chemo-photothermal therapy. LRPmAb had small size (172.2±9.6nm), narrow distribution, and negative ζ-potential (−12.0±0.3mV). In addition, LRPmAb showed pH- and temperature-dependent release profiles. LRPmAb showed significantly enhanced uptake in BT-474 cells, a natural HER2/neu expressing cell line. We found that these LRPmAb were effective in delivering rapamycin and showed higher therapeutic efficacy in breast cancer cells overexpressing HER2/neu receptors compared with cells that did not overexpress these receptors. Furthermore, LRPmAb showed synergistic activity against rapamycin-sensitive and resistant cell lines in vitro. These findings indicated that LRPmAb-mediated drug delivery could improve the therapeutic efficacy against breast cancer and overcome drug resistance.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2017.05.034