Construction Of Hydroxyethyl Starch-Chlorin E6 Nanoparticles And Its Application In Photodynamic Antitumor Research

In recent years,photodynamic therapy has become a powerful means of tumor treatment.However,the effect of photodynamic therapy is still not satisfactory.Most photosensitizers have poor water solubility,limiting the clinical use of photosensitizers to a certain extent.In addition,because photodynamic therapy is a method of local treatment,the photosensitizers need to be delivered to the tumor site,producing reactive oxygen species and then killing the tumor.Therefore,the solubility and delivery efficiency of photosensitizers become two key factors to determine the effect of photodynamic therapy.Nowadays,nanomedicines have been extensively studied in antitumor research because of their ability to enhance drug solubility and targeting.Therefore,researchers apply nanodrug delivery systems to improve the solubility of photosensitizers and facilitate targeted delivery of photosensitizers to tumors,thus boosting the efficacy of photodynamic therapy.However,there are still few nanomedicines available for clinical use,and more controllable and safe nanomedicines need to be developed.In view of the above problems,the hydroxyethyl starch-chlorin e6 nanoparticles were constructed and applied to the antitumor research.Chlorin e6(Ce6)is a commonly used photosensitizer with hydrophobicity.Hydroxyethyl starch(HES)is a semisynthetic polysaccharide with strong water solubility because of its numerous hydroxyl groups.Therefore,hydroxyethyl starch-chlorin e6 conjugates(HES-Ce6)were synthesized by the coupling of Ce6 and HES through ester bond.Compared with Ce6,the solubility of HESCe6 was enhanced.Then,hydroxyethyl starch-chlorin e6 nanoparticles(HES-Ce6 NPs)were prepared by the method of ultrasonic emulsification.Compared with Ce6,HES-Ce6 NPs had stronger photostability and greater reactive oxygen production capacity.Due to the passive targeting of nanoparticles,HES-Ce6 NPs were enriched in tumor tissues,thus improving the killing effect against tumors.Furthermore,HES-Ce6 NPs were characterized by cell assay in this study.The results showed that compared with free Ce6,the HES-Ce6 NPs promoted the cellular uptake of Ce6,facilitated the generation of intracellular reactive oxygen,and enhanced the cytotoxicity.Finally,the in vivo antitumor effect of HES-Ce6 NPs was also studied.The results displayed that HES-Ce6 NPs improved the effect of photodynamic therapy,and achieved strong biological safety simutaneously.In conclusion,the HES-Ce6 NPs were designed in this study to improve the water solubility of Ce6,thereby promoting the delivery of Ce6 to the tumor site.Compared with free Ce6,the photostability of Ce6 was significantly enhanced,thus increasing the production of reactive oxygen,and further improving the effect of photodynamic therapy on tumors.What’s more,HES-Ce6 NPs have a strong potential of clinical transformation due to the good biosafety of hydroxyethyl starch which is used as plasma substitute in clinical practice.