Co-administration of a branched arginine-rich polymer enhances the anti-cancer efficacy of doxorubicin

Huang, X (Huang, Xin)^{[ 1 ]} ; Yan, HS (Yan, Husheng)^{[ 1,2 ]}

COLLOIDS AND SURFACES B-BIOINTERFACES, 2021, 203, 文献号: 111752

DOI: 10.1016/j.colsurfb.2021.111752

摘要

The severe side-effects and drug resistance development of conventional chemotherapy are mainly caused by poor tumor penetration as well as nonspecific biodistribution and insufficient cellular uptake of drugs. Herein a branched arginine-rich polymer was synthesized and co-administration of this polymer with doxorubicin, a model drug of chemotherapeutic agents, overcame simultaneously the three obstacles shown above. Coincubation of the polymer promoted doxorubicin penetration deeply into multicellular tumor spheroids and internalization into cancer cells. Upon co-injection of the polymer with doxorubicin into tumor-bearing mice, the enhanced drug accumulation in and deep penetration into tumor tissue were observed compared to injection of doxorubicin alone. A combined therapy of doxorubicin and the polymer in the treatment of tumor-bearing mice showed a marked enhancement in anticancer efficacy compared to doxorubicin alone. Notably, the treatment with the combination regime reduced the doxorubicin dose to one fifth without reducing the antitumor efficacy compared to the treatment with doxorubicin alone. The possible mechanism of action of the polymer was postulated, in which the guanidinium groups of arginine residues in the polymer may play a pivotal role in the action.