Nano-Drug Delivery System For Combination Therapy

Due to the complexity of cancers,combination chemotherapy as a kind of solution has become more and more important to achieve long-term prognosis and reduced side effects.These multidrug regimens are usually designed to achieve therapeutic synergy,or a medicinal effect that is greater than the sum of each drug treatment alone.Although small-molecule drugs have been the mainstay of such strategies,nanoparticle-formulated drugs have now come of age in the clinic and are inspiring innovative investigations in multidrug delivery.Nanoparticle therapies provide improved drug solubility,reduced systemic toxicity,longer circulation time in the blood,controllable release profiles,and the potential to target specific cells and tissues.Camptothecin and doxorubicin as two kinds of small molecule cancer drugs show high efficiency for cancer therapy.However,because of poor solubility in water,severe side effects and multidrug resistence（MDR）,they suffer from some limitations in clinical application.Base on camptothecin and doxorubicin,we proposed two co-delivery systems.Firstly,a new kind of H₂O₂-responsive HPG-based nanomicelle,which loaded with chemotherapy drugs SN38 and DOX,was develop for effective cancer therapy.Considering the carrier has no therapeutic efficacy,we designed a nano scaled drug delivery system without any carrier.The details are described as follows:（1）H₂O₂-responsive anticancer hyperbranched polymer micelles for co-delivery of the chemotherapeutic drugs SN38 and DOX were constructed.The chemical structure of HPG-2S-SN38 was characterized by ¹H NMR,GPC and DSC.The amphiphilic HPG-2S-SN38self-assembled into nanomicelles which could encapsulate DOX.The size and morphology of HPG-2S-SN38 nanomicelles were characterized by DLS and TEM.The H₂O₂-responsive release behavior of HPG-2S-SN38nanomicelles was measured by DLS.By flow cytometry and fluorescence microscope,the cellular uptake of HPG-2S-SN38 nanomicelles was investigated.The proliferation inhibition of HPG-2S-SN38 nanomicelles was evaluated against MCF-7 cancer cells and Hela cancer cells by MTT assay.（2）Self-tracking nanoscale drug delivery system was developed from irinotecan（Ir）and DOX for cancer therapy.The Ir-DOX nanoscale drug was synthesized by two steps,and the chemical structure was characterized by ¹H NMR,¹³C NMR,LC-MS,FTIR and UV-Vis in detail.The Ir-DOX nanoscale drug could self-assemble into nanoparticles.The fluorescence behavior of Ir-DOX nanoscale drug was investigated by fluorescence spectra.Then,the cellular uptake of Ir-DOX nanoscale drug was evaluated by fluorescence microscopy and flow cytometry.The proliferation inhibition of Ir-DOX nanoscale drug was evaluated against MCF-7/ADR cancer cells by MTT assay.The in vitro results show that Ir-DOX nanoscale drug can overcome the multidrug resistance（MDR）and present an excellent anticancer activity.