Synthesis Of Thermo/Oxidation-responsive Block Copolymers For Anticancer Drug Delivery

Malignant tumor has become one of the main reasons for the current threat to human health.Despite remarkable progresses on cancer therapy,some serious impediments of drugs are still unresolved,such as poor water-soluble properties,bad biocompatibility and severe side effects to normal tissues.Tumor treatments include radiation,chemical drug therapy,traditional Chinese medicine and surgery.However,these therapies are unable to cure most cancer.In recent years,nanomaterials with stimuli-responsibilities have attracted increasing attention in the research community,and are widely used to design smart drug delivery system to target various cancers.In this study,we synthesized a dual thermo/oxidation-responsive polymer and prepared nano-micelles for antitumor drug delivery.Firstly,amphiphilic poly(propylene sulfide)(PPS)and poly(N-isopropy lacrylamide)(PNIPAm)block copolymers were synthesized by combining a living anionic ring-opening and an atom transfer radical polymerization(ATRP)process.The resulting copolymers were self-assembled in water to form aggregated structures,which were characterized by dynamic light scattering(DLS)and scanning electronic microscopy(SEM).DLS measurements showed that heat and oxidants caused a significant change to the hydrodynamic diameter of the particles.Using doxorubicin(DOX)and Nile red as model drugs,the data showed that the release of the Nile red was positively correlated to the concentrations of hydrogen peroxide.At 5 h,the accumulated release of NR increased to 80% with 5% H2O2,38% with 2% H2O2 and 16% with 1% H2O2.Encapsulation and in vitro release of the drug molecules in PPS-PNIPAm nanocarriers confirmed the responsive release profile of such system.Fluorescent spectroscopy data confirmed the liberation of the encapsulated dye,which indicated the decomposition of the particles and validated the concept of stimuli-triggered payload release.Cell uptake of the Dox loaded micelles was investigated with human breast cancer cell line(MCF-7).The results showed Dox-loaded micelles were able to be taken by the cells and mainly resided in the cytoplasma.In the stimulated cells with an elevated level of ROS,more released DOX was observed around the nuclei.At a concentration of 1 mg/mL,the blank micelles showed a high cell viability with A549 lung cancer cells,which suggested good biocompatibility of the synthesized material.On the other hand,in the efficacy experiments,the Dox-loaded micells demonstrated comparable cytotoxicity to free Dox at higher concentrations(up to 5 μg/mL),especially on ROS stimulated cells.These results demonstrated that PPS-PNIPAm nanocarriers possess the capability to respond to two typical stimuli in inflammatory cells: temperature and oxidants and could be used in anticancer drug delivery.