With the advantages of deep tissue penetration and controllability, external X-ray-induced photodynamic therapy (X-PDT) is highly promising for combined cancer therapy. In addition to the low efficiency of photosensitizer (PS)...

No abstract

Introduction: Cancer selectivity, including targeted internalization and accelerated drug release in tumor cells, remains a major challenge for designing novel stimuli-responsive nanocarriers to promote therapeutic efficacy. The hypoxic microenvironment created by photodynamic therapy (PDT) is believed to play a critical role in chemoresistance.Methods: We construct dual-responsive carriers (DANPCT) that encapsulate the photosensitizer chlorin e6 (Ce6) and hypoxia-activated prodrug tirapazamine (TPZ) to enable efficient PDT and PDT-boosted hypoxia-activated chemotherapy.Results and discussion: Due to TAT masking, DANPCT prolonged payload circulation in the bloodstream, and selective tumor cell uptake occurred via acidity-triggered TAT presentation. PDT was performed with a spatially controlled 660-nm laser to enable precise cell killing and exacerbate hypoxia. Hypoxia-responsive conversion of the hydrophobic NI moiety led to the disassembly of DANPCT, facilitating TPZ release. TPZ was reduced to cytotoxic radicals under hypoxic conditions, contributing to the chemotherapeutic cascade. This work offers a sophisticated strategy for programmed chemo-PDT.

Developing bioresponsive nanocarriers with particular tumor cell targeting and on-demand payload release has remained a great challenge for combined chemo-photodynamic therapy (chemo-PDT). In this study, an intelligent nanocarrier (DATAT-NPCe6) responded to hierarchical endogenous tumor pH, and an exogenous red light was developed through a simple mixed micelle approach. The outside TAT ligand was masked to prevent an unexpected interaction in blood circulation. Following the accumulation of DATAT-NPCe6 in tumor tissues, tumor acidity at pH ∼6.5 recovered its targeting ability via triggering DA moiety degradation. Furthermore, the cascaded chemo-PDT was accomplished through light-stimulated nanocarrier disassembly and doxorubicin (DOX) release. Taking advantage of stability and controllability, this work provides a facile approach to designing bioresponsive nanocarriers and represents a proof-of-concept combinatorial chemo-PDT treatment.