Synergistic photothermal-photodynamic-chemotherapy toward breast cancer based on a liposome-coated core-shell AuNS@NMOFs nanocomposite encapsulated with gambogic acid

J Nanobiotechnology. 2022 May 6;20(1):212. doi: 10.1186/s12951-022-01427-4.

Abstract

A multifunctional nanoplatform with core-shell structure was constructed in one-pot for the synergistic photothermal, photodynamic, and chemotherapy against breast cancer. In the presence of gambogic acid (GA) as the heat-shock protein 90 (HSP90) inhibitor and the gold nanostars (AuNS) as the photothermal reagent, the assembly of Zr4+ with tetrakis (4-carboxyphenyl) porphyrin (TCPP) gave rise to the nanocomposite AuNS@ZrTCPP-GA (AZG), which in turn, further coated with PEGylated liposome (LP) to enhance the stability and biocompatibility, and consequently the antitumor effect of the particle. Upon cellular uptake, the nanoscale metal - organic framework (NMOF) of ZrTCPP in the resulted AuNS@ZrTCPP-GA@LP (AZGL) could be slowly degraded in the weak acidic tumor microenvironment to release AuNS, Zr4+, TCPP, and GA to exert the synergistic treatment of tumors via the combination of AuNS-mediated mild photothermal therapy (PTT) and TCPP-mediated photodynamic therapy (PDT). The introduction of GA serves to reduce the thermal resistance of the cell to re-sensitize PTT and the constructed nanoplatform demonstrated remarkable anti-tumor activity in vitro and in vivo. Our work highlights a facile strategy to prepare a pH-dissociable nanoplatform for the effective synergistic treatment of breast cancer.

Keywords: Chemotherapy; Gambogic acid; Gold nanostar; Nanoscale metal−organic framework; Photodynamic therapy; Photothermal therapy.

MeSH terms

  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / metabolism
  • Female
  • Humans
  • Liposomes / therapeutic use
  • Metal-Organic Frameworks*
  • Nanocomposites*
  • Photochemotherapy*
  • Tumor Microenvironment
  • Xanthones

Substances

  • Liposomes
  • Metal-Organic Frameworks
  • Xanthones
  • gambogic acid