摘要
Although surface PEGylation of nanomedicines can decrease serum protein adsorption in vivo,it also blocks uptake by tumor cells.This dilemma could be overcome by employing detachably PEGylated strategy at tumoral extracellular microenvironment to achieve improved cellular uptake while prolonged circulation times.Herein,the amphiphilic graft copolymers with p H-sensitive ortho ester-linked m PEG in side chains and polyurethanes in backbone,can self-assemble into the free and doxorubicin(DOX)-loaded micelles.The p H-sensitive micelles could undergo several characteristics as follows:(i)PEGylated shells for stability in sodium dodecyl sulfonate(SDS)solution;(ii)De PEGylation via degradation of ortho ester linkages at tumoral extracellular pH(6.5)for gradually dynamic size changes and effective release of DOX;and(iii)enhanced cellular uptake and cytotoxicity via positive DOX.Moreover,the dynamic micelles with detachable PEGylation could quickly penetrate the centers of SH-SY5 Y multicellular spheroids(MCs)and strongly inhibit tumor growth in vitro and in vivo,and might be considered as promising and effective drug carriers in tumor therapy.
基金
financially supported by the National Natural Science Foundation of China(No.51803001,51603001 and 51503001)
the Research Foundation of Education Department of Anhui Province of China(No.KJ2018ZD003 and KJ2018A0006)
the Academic and Technology Introduction Project of Anhui University(AU02303203)。
