Preparation And Antitumour Activity Of Camptothecin Protein Nanodrugs

As a lethal disease that has not been overcome worldwide,cancer is a serious threat to human life and health.In recent years,along with advances and discoveries in biomedicine,early screening and diversified treatment modalities have been established to effectively improve the quality of patient survival.However,developing more effective cancer treatments to improve the survival rate of patients is still the focus of current research in the scientific community.Although many nanomedicines have been developed for the delivery of hydrophobic camptothecin(CPT),the pharmacological shortcomings of synthetic nanocarriers have hindered their clinical translation.Designing nature-inspired nanocarriers is a shortcut to address these issues.Since human serum albumin(HSA)is a natural transporter for delivering long-chain fatty acids(LCFAs)and CPT can react with LCFAs to form CPTLCFAs,biomimetic structures of HSA-LCFAs can be easily prepared by the interaction of HSA with CPT-LCFAs,which is beneficial for achieving safe and effective drug therapy.In this work,CPT4 C,CPT9C and CPT18 C were synthesized by modifying fatty acids of different chain lengths(C4,C9 and C18),which can be easily bound to HSA to prepare CPT4C-HSA,CPT9C-HSA and CPT18C-HSA nanodrugs.Experiments and molecular dynamics simulations were used to characterize the interaction between CPT18 C and HSA,and the results showed that CPT18 C could bind tightly to HSA and form stable complexes.Due to albumin mediation,CPT18C-HSA can be effectively endocytosed by cancer cells and induce apoptosis in the most severe cells.In vivo tumor suppression experiments verified that CPT18C-HSA has the most significant antitumor efficacy with significantly reduced physiological toxicity and can be used at high doses without significant side effects.We believe that this bionanodrug has great potential for effective delivery of hydrophobic and/or physiologically unstable drugs.