HER2-targeting two-dimensional black phosphorus as a nanoplatform for chemo-photothermal therapy in breast cancer

Yuanke Liang; Jinxing Liu; Cong Zhao; Hexing Sun; Kaiyuan Huang; Qin Xie; De Zeng; Haoyu Lin; Benqing Zhou

doi:10.1016/j.mtbio.2023.100812

HER2-targeting two-dimensional black phosphorus as a nanoplatform for chemo-photothermal therapy in breast cancer

Mater Today Bio. 2023 Sep 22:23:100812. doi: 10.1016/j.mtbio.2023.100812. eCollection 2023 Dec.

Authors

Yuanke Liang¹, Jinxing Liu², Cong Zhao², Hexing Sun¹, Kaiyuan Huang¹, Qin Xie³, De Zeng³, Haoyu Lin¹, Benqing Zhou²

Affiliations

¹ Department of Thyroid and Breast Surgery, Clinical Research Center, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515000, China.
² Department of Biomedical Engineering, College of Engineering, Shantou University, Shantou, 515063, China.
³ Cancer Hospital of Shantou University Medical College, Shantou, 515031, China.

Abstract

Trastuzumab (Tmab) targeted therapy or its combination with chemotherapy is normally insufficient to elicit a comprehensive therapeutic response owing to the inherent or acquired drug resistance and systemic toxicity observed in highly invasive HER2-positive breast cancer. In this study, we propose a novel approach that integrates photothermal therapy (PTT) with targeted therapy and chemotherapy, thereby achieving additive or synergistic therapeutic outcomes. We utilize PEGylated two-dimensional black phosphorus (2D BP) as a nanoplatform and photothermal agent to load chemotherapeutic drug mitoxantrone (MTO) and conjugate with Tmab (BP-PEG-MTO-Tmab). The in vitro and in vivo experiments demonstrated that the HER2-targeting BP-PEG-MTO-Tmab complexes exhibited desirable biocompatibility, safety and enhanced cancer cell uptake efficiency, resulting in increased accumulation and prolonged retention of BP and MTO within tumors. Consequently, the complex improved photothermal and chemotherapy treatment efficacy in HER2-positive cells in vitro and a subcutaneous tumor model in vivo, while minimized harm to normal cells and showed desirable organ compatibility. Collectively, our study provides compelling evidence for the remarkable efficacy of targeted and synergistic chemo-photothermal therapy utilizing all-in-one nanoparticles as a delivery system for BP and chemotherapeutic drug in HER2-positive breast cancer.

Keywords: Breast cancer; Chemotherapy; Photothermal therapy; Trastuzumab; Two-dimensional black phosphorus.