Preparation Of Acid-responsive Heterogeneous CaP Nanoparticles For Cancer Therapy

Tumors are known as "hard to heal wounds",and they have been a serious threat to human life and health.According to statistics,millions of people die of malignant tumors every year.Although scientists have made great efforts in the field of tumor treatment,the incidence and mortality of tumors remain high.In recent years,with the rapid development of nanomedicine,nanomaterials have been gradually used by scientists in the field of precise diagnosis and treatment of tumors due to their large amount of loaded therapeutic factors and easy modification.Calcium-based nanomaterials have good biocompatibility,biodegradability and other characteristics,showing potential application value in the field of precision tumor therapy.Therefore,based on calcium-based nanoparticles,we have developed different tumor combination therapy nanosystems.The developed nanosystems combine gene therapy,chemotherapy and photothermal therapy to design combination therapy to achieve the purpose of efficient tumor treatment.For cancer treatment,nanocarriers were designed with cationic lipids and polymers to improve the cytosolic delivery efficiency of siRNA.Though the positively charged nanocarriers showed great potential for RNA therapy,it was inevitable to generate the potential cytotoxicity.We constructed a pH-responsive nanoplatform,which co-carried siRNA and anticancer drug(hydroxycamptothecine,HCPT),to integrate gene therapy and chemotherapy for combination cancer therapy.The fluorescent conjugated polymer nanoparticles(CPNPs)modified with cell-penetrating peptides were employed as cores to carry siRNA molecules(siRNA-CPNPs)and track the biodistribution of nanotherapeutics by virtue of fluorescence.Calcium phosphate(CaP)nanocoatings were deposited on the surface of siRNA-CPNPs,followed by loading with HCPT and aptamers targeting cancer cells to obtain a targeted and tumor acid-responsive biocompatible nanoplatform.After the uptake of cancer cells,the CaP nanocoatings were decomposed in the acidic endo/lysosomes to release HCPT,and the siRNA-CPNPs were exposed to facilitate the siRNA endo/lysosome escape and cytoplasm delivery.Results obtained from both in vitro and in vivo studies in tumor inhibition expressed that the combined therapy exhibited a better therapeutic efficacy than any monotherapy.Photothermal therapy(PTT)of tumors has always been favored by scientists.The main principle is to kill tumour cells through the high heat generated by photothermal conversion,but this inevitably damages normal cells around the tumor.We use glucose peroxidase(GOx)as a template for biomineralization to form CaP nanoparticles loaded with Capsaicin.Subsequently,a layer of gold nanoclusters was deposited on the surface of the nanoparticles to construct a photothermal-chemical kinetics combined therapy nanoplatform that could be degraded in the tumor microenvironment.The photothermal nanoplatform has absorption in the near-infrared region,Because capsaicin has the function of lowering the temperature tolerance threshold of cells,the nanoplatform has the characteristics that low temperature can kill tumor cells without damaging normal cells.After being degraded in the tumor microenvironment,the nanoplatform exposed GOx to exert its chemokinetic(CDT)therapeutic function.This method will provide a new idea for green treatment of tumors.