Synthesis And Properties Of Stimuli-responsive Nanocarriers For Controlled Anticancer Drug Delivery

Nanodrug delivery systems have been considered as one of the most prospective platforms for cancer chemotherapy.They have unique physicochemical and biological properties,such as increased drug accumulation in solid tumors by the enhanced permeability and retention effect and decreased side effects.Polymeric carriers have been widely studied because of their biodegradability and good biocompatibility.However,conventional polymer carriers have disadvantages in holding the drug being transported stably in the bloodstream,tumor targeting and controlled drug release.To achieve these requirements,various intelligent drug carriers have been constructed for anticancer drug delivery.They are sensitive to the microenvironment stimuli(pH,enzymes,redox,etc.)of tumor tissue or external environment stimuli(light,etc.),which can control the release of encapsulated drugs.Here,three novel types of stimuli-responsive systems for controlled drug release based on enzymes,redox and near-infrared light were prepared by designing the molecular structure of polymer carriers and using doxorubicin or camptothecin as model drug.Their properties including drug release,cellular uptake and cytotoxicity were evaluated in vitro.The specific contents are as follows:(1)Doxorubicin was mixed with monomer and the crosslinker in response to one of the matrix metalloproteases(MMP-2).Doxorubicin nanocapsules were prepared through in situ radical polymerization.Doxorubicin nanocapsules were about 200 nm in diameter with spherical structure.The polymer shell was gradually degraded with the help of MMP-2,accelerating the doxorubicin release.In addition,Doxorubicin nanocapsules were internalized by cells and could escape from the lysosome compartment,resulting in prominent cell death.(2)Camptothecin was mixed with monomer and the crosslinker with disulfide bond,which formed the polymer shell through in situ radical polymerization.Camptothecin nanocapsules were spherical with about 200 nm in diameter.Drug release behavior of camptothecin was related to glutathione.Faster dissolution rate and more cumulative dissolution were attributed to higher concentration of glutathione.Moreover,camptothecin nanocapsules were also internalized by cells and could escape from the lysosome compartment and then induced apoptosis effectively.(3)Hollow mesoporous Prussian blue nanoparticles were surface modified using thiolated polymers,fabricating near-infrared light and redox-responsive organic-inorganic composite nanocapsules.Doxorubicin was loaded into nanocapsules and the loading content was up to 42%,due to distinctive structure of hollow mesoporous Prussian blue.With the existence of 808 nm laser irradiation and glutathione,the rate and amount of drug release from nanocapsules were significantly increased.Cellular uptake and cytotoxicity experiments further confirmed the positive role of the photothermal properties in accelerating drug release and killing the tumor cells.