To achieve highly selective synergistic chemotherapy attractive for clinical translation,the precise polymeric nano-prodrugs(PPD-NPs)were successfully constructed via the facile crosslinking reaction between p H-sensi...To achieve highly selective synergistic chemotherapy attractive for clinical translation,the precise polymeric nano-prodrugs(PPD-NPs)were successfully constructed via the facile crosslinking reaction between p H-sensitive poly(ortho ester)s and reduction-sensitive small molecule synergistic prodrug(Pt(IV)-1).PPD-NPs endowed the defined structure and high drug loading of cisplatin and demethylcantharidin(DMC).Moreover,PPD-NPs exhibited steady long-term storage and circulation via the crosslinked structure,suitable negative potentials and low critical micelle concentration(CMC),improved selective tumour accumulation and cellular internalization via dynamic size transition and surficial amino protonation at tumoural extracellular p H,promoted efficient disintegration and drug release at tumoural intracellular p H/glutathione,and enhanced cytotoxicity via the synergistic effect between cisplatin and DMC with the feed ratio of 1:2,achieving significant tumour suppression while decreasing the side effects.Thus,the dynamic crosslinked polymeric nano-prodrugs exhibit tremendous potential for clinically targeted synergistic cancer therapy.展开更多
基金supported by the Anhui Engineering Technology Research center of Biochemical Pharmaceutical(Bengbu Medical College)the National Natural Science Foundation of China(No.51803001)the Research Foundation of Education Department of Anhui Province of China(No.KJ2018ZD003,KJ2018A0006 and KJ2019A0015)the Academic and Technology Introduction Project of Anhui University(AU02303203)。
文摘To achieve highly selective synergistic chemotherapy attractive for clinical translation,the precise polymeric nano-prodrugs(PPD-NPs)were successfully constructed via the facile crosslinking reaction between p H-sensitive poly(ortho ester)s and reduction-sensitive small molecule synergistic prodrug(Pt(IV)-1).PPD-NPs endowed the defined structure and high drug loading of cisplatin and demethylcantharidin(DMC).Moreover,PPD-NPs exhibited steady long-term storage and circulation via the crosslinked structure,suitable negative potentials and low critical micelle concentration(CMC),improved selective tumour accumulation and cellular internalization via dynamic size transition and surficial amino protonation at tumoural extracellular p H,promoted efficient disintegration and drug release at tumoural intracellular p H/glutathione,and enhanced cytotoxicity via the synergistic effect between cisplatin and DMC with the feed ratio of 1:2,achieving significant tumour suppression while decreasing the side effects.Thus,the dynamic crosslinked polymeric nano-prodrugs exhibit tremendous potential for clinically targeted synergistic cancer therapy.
