Construction Of NIR-Ⅱ Photoresponsive Hyaluronic Acid-based Hydrogel And Its Application In Postoperative Treatment Of Tumor

As the most invasive skin cancer,melanoma poses a great threat to human life and health.Currently,the common treatment for melanoma is surgical resection followed by chemotherapy(CT)and radiotherapy(RT)to prevent recurrence caused by residual tumor cells after surgery.However,surgical resection will lead to large skin defects and lead to wound infection.Systemic chemotherapy and radiotherapy lack controllable and precise treatment of tumor tissue,resulting in poor treatment effect and serious physiological side effects for patients.Photothermal therapy(PTT)has the advantages of precise and controllable,simple and efficient,and few side effects.However,the responsiveness of the first near-infrared window(NIR-I)makes its tissue penetration ability weak and it is difficult to completely remove tumor cells.Aiming at the above problems,this paper constructed a near-infrared second window(NIR-Ⅱ)light-responsive hyaluronic acid-based multifunctional hydrogel that prevents the recurrence and metastasis of melanoma after operation,and integrates hemostasis,antibacterial and wound healing.glue.The thesis is mainly divided into the following three parts:(1)The water-dispersible and NIR-II photoresponsive HP@PNPG was prepared by coating poly-N-phenylglycine(PNPG)with phenylboronic acid-modified hyaluronic acid(HP),and then the hydrophobic drug curcumin(Cur)was used to the1,3 diketone group of HP@PNPG and the boronic acid group of HP@PNPG are dynamically connected through complexation to obtain HP@PNPG/Cur,and finally with natural polyphenol tannic acid(TA)by forming dynamic borate bond to prepare HP@PNPG/Cur-TA hydrogel.TA a large number of catechol groups make the hydrogel has good adhesion(30.2 k Pa)and antioxidant(>96.2%).The dynamic reversibility of borate ester bonds endows hydrogels with good self-healing properties,injectability,temperature/p H responsiveness,light-controlled drug release properties,etc.The organic acid doping of HP red-shifted the absorption peak of PNPG to NIR-II,so the hydrogel showed excellent photothermal conversion ability of NIR-II photoresponse(η=42.57%).(2)Studies have shown that the prepared hydrogel has good cytocompatibility(L929 cell viability > 85%)and blood safety(hemolysis rate < 3%).Under the irradiation of 1064 nm laser,HP@PNPG/Cur-TA hydrogel showed excellent photothermal-chemotherapy synergistic anti-tumor effect,and the killing rate of B16 melanoma cells was as high as 99.54%.In addition,the hydrogel exhibited excellent in vitro antibacterial activity(inhibition rate >99%)based on the combined antibacterial activity of TA and Cur.Therefore,HP@PNPG/Cur-TA hydrogel has the potential to inhibit residual tumor recurrence and prevent wound infection in the postoperative treatment of melanoma.(3)Hydrogels were investigated for their in vivo hemostatic effects,inhibition of postoperative melanoma recurrence,and promotion of infected wound healing.The results showed that the hydrogel had an excellent hemostatic effect(the amount of bleeding in the liver and tail wounds decreased from 114.6 mg and 184.8 mg to 15.8mg and 10.3 mg,respectively).HP@PNPG/Cur-TA hydrogel,as a combined photothermal-chemotherapy platform,can effectively kill tumor tissue,showing excellent melanoma inhibitory effect,and no signs of tumor recurrence were seen 14 days after surgery.In addition,the hydrogel was significantly effective in promoting the healing of staphylococcus aureus-infected wounds(wounds were completely healed on day 14).