| Multidrug resistance(MDR)is considered to be the toughest obstruct hinders the cancer therapy efficiency and leads to high recrudescence rate.In the multidrug resistant(MDR)cancer treatment field,chemo/photo-synergistic therapy has emerged as a significant research focus recently.Firstly in this work,a mesoporous carbon nanoparticles(MCNs)based,anti-cancer agent doxorubicin(DOX)loaded nano-drug delivery system(DOX@MCNs)is designed for enhanced anti-MDR effect via chemo/photothermal/photodynamictherapy.Mesoporouscarbon nanoparticles(MCNs)were prepared by low-concentration hydrothermal route.The morphology,surface properties and the near infrared(NIR)induced photothermal effect were evaluated.DOX was loaded into MCNs to fabricate DOX@MCNs via adsorption method.Drug loading capacity was calculated by UV,and drug release profile was investigated by dialysis method.We chose MCF-7/ADR cells to investigate intracellular DOX@MCNs uptake and distribution by confocal laser microscopy and evaluate cytotoxicity of DOX@MCNs by MTT method.Intracellular ROS level under NIR irradiation was measured by flow cytometry.The results showed that:MCNs particle size was about 90 nm.Surface carboxyl existed.Specific surface area was 541.62 m~2/g,pore volume was0.34 cm~3/g,pore size was 2.5 nm.Significant photothermal effect was demonstrated.Drug loading capacity of DOX@MCNs was as high as47.4%,pH and NIR responsive release profiles can be observed.DOX@MCNs can promote DOX uptake and nuclear distribution in MDF-7/ADR cells and induce the generation of ROS under NIR irradiation,and had an enhanced inhibitory effect on drug resistantant tumor cells.Then,a near infrared(NIR)stimuli-responsive mesoporous carbon nanoparticles(MCNs)based,anti-cancer agent doxorubicin(DOX)loaded,PEG-poly(curcumin-dithiodipropionic acid)(PEG-PCDA)coated multi-functional nano-drug delivery system(PEG-PCDA/DOX@MCNs)was successfully developed for chemo/photothermal/photodynamic synergistic therapy.It performed versatile properties of high drug loading capacity(~47.4%),pH responsive drug releasing,excellent stability and biocompatibility.What's more,the disulfide bond linked PEG-PCDA playedasasmart“gatekeeper”role,whichendowed PEG-PCDA/DOX@MCNs with tumor-site-specific glutathione(GSH)responsive drug releasing property(76.9%cumulative release in 5 mM GSH medium vs 34.4%in non-GSH one).Moreover,due to the inherent photothermal effect of MCNs,a sudden and repetitively enhanced DOX release was observed as the 808 nm NIR“switched on/off”.In particular,PEG-PCDA/DOX@MCNs were further demonstrated to induce the generation of reactive oxygen species(ROS)in vitro,known as photodynamic effect,which could kill the tumor cells directly with minimumside-effect.Combiningthemeritsabove,PEG-PCDA/DOX@MCNs showed promoted cytotoxicity,enhanced DOX uptake,weakened efflux and increased accumulation in multidrug resistant cancer,and moreover,an obvious tendency to distribute towards nucleus was observed after NIR irradiation.Taken together,this novel MCNs based,tumor environment intelligently responsive,chemo/photothermal/photodynamic synergistic drug delivery system is a potential MDR cancer treatment agent both now and future. |
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