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  2. Supramolecular Engineering of Molecular Inhibitors in an Adaptive Cytotoxic Nanoparticle for Synergistic Cancer Therapy

Supramolecular Engineering of Molecular Inhibitors in an Adaptive Cytotoxic Nanoparticle for Synergistic Cancer Therapy

  • ACS Appl Mater Interfaces. 2020 Jan 8;12(1):1707-1720. doi: 10.1021/acsami.9b20178.
Weidong Han 1 Linlin Shi 1 Binbin Xie 1 Jianqin Wan 2 Lulu Ren 1 Yuchen Wang 2 Xiaona Chen 2 Hangxiang Wang 1
Affiliations

Affiliations

  • 1 Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine , Zhejiang University , Hangzhou , 310016 , PR China.
  • 2 Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, School of Medicine , Zhejiang University , Hangzhou , 310003 , PR China.
Abstract

Combinatorial regimens that rationally pair molecular inhibitors with standard cytotoxic chemotherapeutics are used to improve therapeutic outcomes. Simultaneously engineering these therapies within a single nanocarrier that spans cytotoxic, antiangiogenic, and anti-invasive mechanisms and that enables the delivery of unique drug combinations remains a technical challenge. In this study, we developed a simple and broadly applicable strategy in which ultrastable cytotoxic nanoparticles with an established excellent antitumor efficacy and π-rich inner core structure supramolecularly stabilized the antiangiogenic molecular inhibitor apatinib to create a synergistic Drug Delivery system (termed sTKI-pSN38). This small-sized nanoparticle accomplished the sequential release of both encapsulated drugs to exert antimetastatic, antivascular, and cytotoxic activities simultaneously. In xenograft models of hepatocellular carcinoma, a single intravenous administration of sTKI-pSN38 elicited robust and durable tumor reduction and suppressed metastasis to lymph nodes. Interestingly, sTKI-pSN38 treatment alleviated intratumoral hypoxia, which could contribute to impaired tumor metastasis and reduced drug resistance. Collectively, this nanotherapeutic platform offers a new strategy for Cancer therapy by simply engineering a drug cocktail in conventional nanoparticles and by enabling the spatiotemporal modulation of drug release to enhance the synergy of the combined drugs.

Keywords

apatinib; cancer nanomedicine; cytotoxic drug; drug combination; metastasis inhibition.

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