Abstract
Purpose
Photodynamic therapy (PDT) has been an attractive strategy for skin tumor treatment. However, the hypoxic microenvironment of solid tumors and further O2 consumption during PDT would diminish its therapeutic effect. Herein, we developed a strategy using the combination of PDT and hypoxia-activated bioreductive drug tirapazamine (TPZ).
Methods
TPZ was linked to DSPE-PEG-NHS forming DSPE-PEG-TPZ to solve leakage of water-soluble TPZ and serve as an antitumor agent and monomer molecule further forming the micellar. Chlorin e6 (Ce6) was loaded in DSPE-PEG-TPZ forming DSPE-PEG-TPZ@Ce6 (DPTC). To further improve tumor infiltration and accumulation, hyaluronic acid was adopted to make DPTC-containing microneedles (DPTC-MNs).
Results
Both in vitro and in vivo studies consistently demonstrated the synergistic antitumor effect of photodynamic therapy and TPZ achieved by DPTC-MNs. With laser irradiation, overexpressions of PDT tolerance factors NQO1 and HIF-1α were inhibited by this PDT process.
Conclusion
The synergistic effect of PDT and TPZ significantly improved the performance of DPTC-MNs in the treatment of melanoma and cutaneous squamous cell carcinoma and has good biocompatibility.
Abbreviations
CLSM, Confocal microscopy; DLS, Dynamic light scattering; DMEM, Dulbecco’s modified Eagle’s medium; DPTC: DSPE-PEG-TPZ forming DSPE-PEG-TPZ@Ce6; DPTC-MNs: DPTC-containing microneedles; FBS, Fetal bovine serum; H&E, Hematoxylin and eosin; HA, Hyaluronic acid; MNs, Microneedles; NHS, N-hydroxysuccinimide; PBS, Phosphate-buffered saline; ROS, Reactive oxygen species; SEM, Scanning electron microscopy; TEM, Transmission electron microscopy.
Acknowledgments
This work was supported by the National Natural Science Foundation of China [grant numbers 82003295, 82172706, 82073385], the Science and Technology Commission of Shanghai Municipality [grant numbers 20DZ2255200, 21S21900900, 22S21902700, 23S11901300], and Shanghai Sailing Program [grant number 19YF1443700].
Disclosure
The authors report no conflicts of interest in this work.