Melanoma is a highly aggressive cutaneous cancer with high rates of mortality.Currently,the widely applied traditional therapeutics such as surgery excision,chemotherapy,and radiotherapy still suffered from several problems including high risk of infection,great threat of recurring,severe adverse effects,undesirable drug resistance and so on.Wherefore,treatment of melanoma involves not only the elimination of skin cancer cells,but also repairing tumor-initiated skin defects and avoiding the bacteria invasion.In order to overcome the above problems,this thesis proposes an injectable multifunctional hydrogel with tumor therapy,antibacterial treatment and wound healing properties for simultaneous eradicating melanoma and promoting wound healing of tumor-initiated skin defects.Based on this,the work content is divided into the following three parts:(1)iron-doped polyaniline(PANI(Fe))tethered with guar gum(GG)chains by electrostatic and hydrogen bonding interactions is employed as a building unite for constructing a superior hydrogel(GG@PANI(Fe)-borax)crosslinked by borate/didiol bonds.Due to the dynamic and reversible properties of boronate bonds,the GG@PANI(Fe)-borax was endowed with self-healing property,injectability,and reversible gel-sol transformations under thermal or p H.Furthermore,taking advantage of the second near-infrared(NIR-Ⅱ)responsive photothermal conversion capability of GG@PANI(Fe)(η=44.81%),accompany with the photothermal-enhanced Fenton reaction and high cytotoxic·OH generation ability in the H2O2-enriched tumor microenvironment induced by PANI(Fe)applied to CDT.(2)CDDP/GG@PANI(Fe)-borax has NIR-triggered drug release properties and in vitro synergistic antitumor effects.First,GG@PANI(Fe)-borax has excellent cytocompatibility in vitro(L929 cell viability>95%).Subsequently,GG@PANI(Fe)-borax+H2O2 could produce a large amount of·OH available for CDT in B16 cells.Therefore,CDDP/GG@PANI(Fe)-borax has significant in vitro synergistic anti-tumor effect under 1064 nm laser irradiation,and the synergistic tumor cell killing rate was up to 98.2%,indicating that combined NIR light irradiation and loaded anticancer drugs could achieve synergistic PTT/CDT/chemotherapy treatment on melanoma cells.In addition,the in vitro cell scratch test and antibacterial activity test showed that the hydrogel has potential application in promoting wound healing.(3)To investigate the combined anti-tumor effect of CDDP/GG@PANI(Fe)-borax in B16 tumor-bearing mice in vivo.The in vivo anti-tumor results showed that after combined with 1064 nm laser irradiation,the hydrogel showed stronger anti-tumor effect with 98.8%tumor inhibition,which could achieve the synergistic effect of PTT/CDT/chemotherapy synchronization on melanoma treatment and promotion of wound healing.In addition,the hydrogel not only promoted the healing of infected wounds,but also effectively eradicated the infection of Staphylococcus aureus.In summary,GG@PANI(Fe)-borax may be used simultaneously for eradication of the tumor cells,preventing wound infection and accelerating the tissue healing.This work offers an effective strategy to prepare injectable self-healing multifunctional hydrogels for skin-tumor therapy,bacterial infection treating,and skin wound healing. |