%0 Journal Article
%T In vitro/vivo antitumor study of modified-chitosan/carboxymethyl chitosan "boosted" charge-reversal nanoformulation.
%A Li L
%A Zhang P
%A Li C
%A Guo Y
%A Sun K
%J Carbohydr Polym
%V 269
%N 0
%D Oct 2021 1
%M 34294300
%F 10.723
%R 10.1016/j.carbpol.2021.118268
%X Major obstacles in the development of nanoformulations as efficient drug delivery systems are the rapid clearance from blood circulation and lysosomal entrapment. To overcome these problems, a polysaccharide-based core-shell type charge-switchable nanoformulation (CS-LA-DMMA/CMCS/PAMAM@DOX) is constructed to improve antitumor efficacy of DOX. By applying carboxymethyl chitosan (CMCS) as bridge polymer and negatively charged chitosan-derivative as outer shell, the stability and pH-sensitivity of this nanoformulation is promisingly enhanced. Furthermore, the positively charged PAMAM@DOX could escape from lysosomes via "proton sponge effect" and "cationic-anionic interaction with lysosome membranes". Admirable cellular uptake and high apoptosis/necrosis rate were detected in this study. In vitro assays demonstrate that the CS-LA-DMMA/CMCS/PAMAM@DOX was internalized into HepG2 cells predominantly via the clathrin-mediated endocytosis pathway. Excitingly, in vivo studies showed that high accumulation of CS-LA-DMMA/CMCS/PAMAM@DOX in tumor tissue led to enhanced tumor inhibition. Compared with free DOX, the tumor inhibition rate of nanoformulation was improved up to 226%.