Microenvironment Responsive Copper Sulfide Composite Nanoparticles For Tumor Deep Phototherapy

Nanomaterial-mediated photothermal therapy has been widely used to treat cancer research due to its small invasiveness and specific spatial and temporal selectivity.However,in the tumor microenvironment,the interstitial fluid pressure is high,the extracellular matrix is dense,the cell growth is erosive and fibrotic,so that large-scale photothermal nanomaterials can not reach deeper tumor tissue,thus affecting the photothermal treatment of deep tumor.And larger size photothermal nanomaterials remain in the body for long periods of time or even permanently after treatment,creating a non-negligible toxicity problem for healthy tissues/organs.Therefore,it is necessary to design a photothermal nanomaterial that can penetrate deep tumor tissue and and rapidly degrade,which is especially important in cancer treatment research.In this study,we designed a microenvironment responsive degradable copper sulfide and gelatin nanocomposite(PRDCuS@AG,d=240 nm)for deep tumor phototherapy.PRDCuS@AG can be degraded and releases 9 nm CuS-dendrimer composite particles(PRDCuS)by metal matrix proteases treatment in tumor tissues,and has synergistic therapeutic properties of phototherapy and chemotherapy in the deep tumor.Compared with traditional inorganic photothermal materials,this nano-drug has the following advantages:1)It has specific spatial and temporal selectivity,and can improve the EPR effect while effectively accumulating PRDCuS in the deep part of the tumor;2)arginine is exposed on the surface of the degraded PRDCuS,which enhances the uptake of nanoparticles into the cells and the penetration of deep tumors,and can effectively treat the deep tumor(inhibition rate is 97%);3)Moreover,under the stimulation of photothermal and tumor microenvironment,PRDCuS can be rapidly degraded into small particles of 3 nm,which can be quickly removed from the body and avoid toxic side effects on normal tissues.This multi-stimulation response and strong tumor tissue penetration properties of PRDCuS@AG can effectively inhibit tumor growth,metastasis and recurrence through combination therapy,opening up a new way for the construction of biodegradable dual-mode phototherapy materials.