The combined effect of hypoxia activation and radiosensitization by a multifunctional nanoplatform system enhances the therapeutic efficacy of chemoradiotherapy in pancreatic cancer.

[BACKGROUND] Pancreatic cancer is a highly malignant tumor, which is still a major global health problem. Chemotherapy and radiotherapy are regularly used in adjuvant therapy for pancreatic cancer but their therapeutic efficacy is limited.

[METHODS] In the present study, nanoparticle（MSN-AuNPs） was used as a drug carrier loaded with tirapazamine(TPZ) and hyaluronic acid (HA) to synthesize a multifunctional nanoplatform HA@TPZ-MSN-AuNPs (HTMA) for hypoxia activation and radiotherapy sensitization, which can be combined with radiotherapy therapy and synergistically enhance the therapeutic effect in pancreatic cancer. The anti-tumor performance of the nano platform was verified by in vivo and in vitro experiments.

[RESULT] First, the HA@TPZ-MSN-AuNPs (HTMA) was successfully synthesized. Drug release experiments showed that acidic environment and hyaluronidase promoted drug release in the nanoplatform. In vitro experiments, CCK-8, live-dead staining, clonal formation assay and flow cytometry confirmed the combined anti-tumor effect of hypoxia activation and radiotherapy sensitization with HTMA. In the drug uptake experiment, the nanoplatform showed the function of targeting and binding pancreatic cancer cells. In vivo, HTMA demonstrated good antitumor properties and good biocompatibility.

[CONCLUSIONS] The nanoplatform had a good targeting effect and synergistic anti-tumor effect. The combination of hypoxia activation and radiotherapy sensitization is a promising strategy for the treatment of pancreatic cancer.