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

Abstract

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 +/- 9.6 nm), narrow distribution, and negative zeta-potential (-12.0 +/- 0.3 mV). 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. (C) 2017 Elsevier B.V. All rights reserved.