Amphiphilic Combination Chemotherapy Dilivery System For Synergistic Cancer Therapy

Combination chemotherapy has become more and more important in cancer treatment and attracted broad attention among researchers for overcoming the limitations of monotherapy including drug-mitigating response,serious side effects,and poor therapeutic efficacy.However,due to the present cocktail administration of combination chemotherapy,the unique pharmacokinetics of individual drugs,which could give rise to noncoordinated biodistribution and suboptimal drug combination at the tumor sites,have limited the enhancement of therapeutic efficacy.Now many kinds of combination drug delivery systems have been developed to address this issue,yet most of them encounter numerous barriers regarding low drug loading efficiency and complex preparation process with high cost,which keep them away from mass production.Based on the previous research,we proposed a new carrier-free strategy for combination chemotherapy dilivery system.We conjugated a hydrophilic anticancer drug and a hydrophobic anticancer drug with synergistic anticancer effect,which could self-assemble into nanoparticles.This nanoparticle could diliver synergistic ratio of drugs to cancer cells,leading to remarkable synergistic anticancer efficacy.The details are as follows:?1?Preparation of chlorambucil-floxuridine self-assembled nanoparticles and study of the synergistic anticancer effect.The chlorambucil-floxuridine conjugate was synthesized by esterification.The chemical structure was characterized by ¹H NMR,¹³C NMR,MS,FTIR and UV-Vis.Due to its inherent amphiphilicity,the conjugate could self-assemble into nanoparticles.The size and morphology of this nanoparticle were characterized by DLS and TEM.In vitro studies demonstrated synergistic anticancer efficacy of the chlorambucil-floxuridine nanoparticles including improved cell apoptosis and effective inhibition of cancer cell proliferation.?2?Preparation of camptothecin-floxuridine self-assembled nanoparticles and study of the synergistic anticancer effect.Camptothecin and floxuridine were connected to the diglycolic anhydride linker through two steps of esterification.The chemical structure was characterized by ¹H NMR,¹³C NMR,MS,FTIR and UV-Vis.Due to its inherent amphiphilicity,the conjugate could self-assemble into nanoparticles.The size and morphology of this nanoparticle were characterized by DLS and TEM.In vitro studies demonstrated synergistic anticancer efficacy of the camptothecin-floxuridine nanoparticles including improved cell apoptosis,varied cell cycle arrest,as well as effective inhibition of cancer cell proliferation.