| Cancer is one of the main diseases that seriously endanger human life and health and cause human death,and its incidence is increasing year by year.As one of the methods of conventional clinical treatment of cancer,chemotherapy(CT)has problems such as poor targeting,large side effects,and multi-drug resistance,which limit its efficacy.Photothermal therapy(PTT)has attracted widespread attention because of its non-invasive,easy operation,non-invasive,local selectivity,low drug resistance,and few side effects.Photothermal therapy is mainly through specific wavelength laser irradiation of photothermal agent(PTA)enriched at the lesion site,PTA converts the absorbed light energy into heat energy,resulting in local high heat at the irradiation site,thereby inducing apoptosis and/or necrosis of cancer cells.However,during PTT treatment,cancer cells will produce heat shock protein for self-protection,resulting in low treatment efficiency and easy recurrence.Therefore,for tumors with complexity,diversity and heterogeneity,monotherapy can not achieve the ideal therapeutic effect,and PTT/CT combination therapy can overcome the limitations of monotherapy,PTT generated local high temperature while killing cancer cells,accelerating the release of chemotherapy drugs,enhancing the uptake of chemotherapy drugs by cancer cells,and effectively avoiding the resistance of chemotherapy drugs,thereby improving the efficiency of tumor treatment.In addition,controlling the precise release of drugs in the lesion site and increasing the local drug concentration are also effective ways to improve the efficiency of tumor treatment.This paper focuses on the design and preparation of temperature-sensitive nanoparticles based on caproylated ethylene glycol chitosan(HGC)to achieve controlled drug release and its application in tumor PTT/CT combination therapy,the main research contents are as follows:1.Gold nanoparticles(AuNPs)were used as the core and temperature-sensitive HGC as the shell.CT drugs(DOX)and photothermal preparations(ICG)were coated on the surface of AuNPs to form temperature-sensitive nanoparticles(AuNPs@HGC-DOX-ICG)for PTT/CT combination therapy.HGC shell can control the size of nanoparticles and DOX release behavior.The results showed that AuNPs@HGC-DOX-ICG had a spheroid structure,and DOX and ICG loading were35.7% and 16.6%,respectively.Under 808 nm laser irradiation,AuNPs@HGC-DOX-ICG showed obvious size shrinkage and DOX release behavior with increasing temperature,and the photothermal conversion efficiency was 19.1%.In vitro cell experiments showed that AuNPs@HGC-DOX-ICG showed higher cytotoxicity to He La and Si Ha cells than PTT and CT alone.2.Cu sulfide nanoparticles(CuS)with photothermal properties were designed and prepared as the core and HGC as the shell.CT drugs(doxorubicin,DOX)were coated on the surface of CuS to form thermosensitive nanoparticles(CuS@HGC-DOX)for PTT/CT collaborative treatment of tumor.The HGC shell could control the size and release behavior of DOX.The results showed that CuS@HGC-DOX was spheroid structure and DOX loading was 27.1%.At 880 nm laser irradiation,CuS@HGC-DOX showed obvious size shrinkage and DOX release behavior,as well as high photothermal conversion efficiency(35.4%,based on indocycyanine green)with increasing temperature,and showed good photostability and obvious photothermal activity after 5 cycles of laser irradiation.In vitro cell experiments showed that CuS@HGC-DOX showed higher cytotoxicity to He La and Si Ha cells than PTT and CT alone. |
