Stimuli responsive PEGylated bismuth selenide hollow nanocapsules for fluorescence/CT imaging and light-driven multimodal tumor therapy

Stimuli-responsive therapeutic nanosystems exhibit enhanced selectivity and higher biosafety for cancer theranostics via recognizing exogenous or endogenous tumor-associated factors. Herein, we developed a multifunctional nanocomplex (Bi2Se3@PEG/DOX/Ce6 nanocapsules, or BPDC NCs in brief) which was constructed by loading chlorin e6 (Ce6) and doxorubicin (DOX) into PEGylated hollow bismuth selenide nanocapsules. Upon administration of BPDC NCs, composite laser irradiation can effectively activate the local hyperthermia generation and the yield of cytotoxic reactive oxygen species (ROS). In another aspect, on-demand drug release can be triggered in a mild acidic tumor microenvironment or by thermal shock. Moreover, imaging and navigation with respect to infrared thermography, computed tomography (CT) and fluorescence imaging may potentially monitor the biodistribution of BPDC NCs, thanks to the local hyperthermia generation, fluorescence emission of Ce6 and high Z-element of bismuth. Finally, we demonstrated tumor site-specific photothermal therapy (PTT), photodynamic therapy (PDT) and chemotherapeutic effects for highly efficacious tumor suppression with minimized systemic toxicity. Taken together, these findings indeed provide insights that can broaden the application of Bi2Se3 nanocapsules for cancer management and precision medicine.