Versatile biomimetic cantharidin-tellurium nanoparticles enhance photothermal therapy by inhibiting the heat shock response for combined tumor therapy

Abstract

The heat shock response (HSR) induced by photothermal therapy (PTT), which can cause tumor cells to resist apoptosis, has increasingly attracted the attention of researchers. Synergistic treatment of tumors using multiple means to improve therapeutic efficiency would be a promising strategy for effective cancer treatment. In this study, a cancer cell membrane-camouflaged nanocarrier was developed and loaded with tellurium (Te) and cantharidin (CTD) for efficient combinatorial therapy. The designed nanoparticles (m-CTD@Te) used a 4T1 cell membrane coating as the shell with homologous targeting capability, CTD as an the HSR inhibitor and antitumor drug, and Te as a PTT and photodynamic therapy (PDT) photosensitizer. An in vivo study indicated that the tumor inhibition rate of this combinatorial therapy could reach approximately 82.3% in 4T1 mammary tumor models. This study suggested that m-CTD@Te, as a versatile biomimetic nanoplatform, provides a new alternative for more precise and effective tumor treatment. STATEMENT OF SIGNIFICANCE: In this work, we constructed cell membrane-coated biomimetic nanoparticles (m-CTD@Te) to suppress cancer effectively through synergistic treatment. The developed m-CTD@Te nanoparticles presented strong homologous targeting capabilities. The encapsulated Te triggered PDT and PPT under the near-infrared laser irradiation. Subsequently, the PTT triggered the release of CTD, which could suppress the HSR of tumor and achieve chemotherapy. In addition, due to the presence of outer cell membrane coating, these m-CTD@Te nanoparticles showed good biocompatibility to healthy cells.

Keywords: Biomimetic; Heat shock response (HSR); Photothermal therapy (PTT); Synergistic treatment; Tellurium (Te).