Combretastatin A4 phosphate(CA4P)is a potent vascular disrupting agent with good water solubility.However,it is only effective at high doses,which decreases clinical applicability.Herein,we designed stable CA4P polyme...Combretastatin A4 phosphate(CA4P)is a potent vascular disrupting agent with good water solubility.However,it is only effective at high doses,which decreases clinical applicability.Herein,we designed stable CA4P polymeric nanoparticles(CA4P NPs)consisting of various cholesterol derivatives,and with a drug loading efficacy of 93%.The nanoparticles released CA4P in a sustained manner and achieved a 72%inhibition rate in the murine H22 liver tumor model,which was about 2.9-fold higher than that of free CA4P(24.6%).Furthermore,the carrier components of CA4P NPs were metabolized to arginine,cholesterol,ethanol and poly(ethylene glycol)in vivo;therefore,the CA4P NPs are safe and have significant potential for clinical translation.展开更多
基金financially supported by the Ministry of Science and Technology of China(No.2022YFE0110200)the Natural Science Foundation of Hunan Province of China(No.2021JJ30680)the National Natural Science Foundation of China(Nos.52203198,52025035 and 52103195)。
文摘Combretastatin A4 phosphate(CA4P)is a potent vascular disrupting agent with good water solubility.However,it is only effective at high doses,which decreases clinical applicability.Herein,we designed stable CA4P polymeric nanoparticles(CA4P NPs)consisting of various cholesterol derivatives,and with a drug loading efficacy of 93%.The nanoparticles released CA4P in a sustained manner and achieved a 72%inhibition rate in the murine H22 liver tumor model,which was about 2.9-fold higher than that of free CA4P(24.6%).Furthermore,the carrier components of CA4P NPs were metabolized to arginine,cholesterol,ethanol and poly(ethylene glycol)in vivo;therefore,the CA4P NPs are safe and have significant potential for clinical translation.
