7 research outputs found

    Rational Design of Multi-Stimuli-Responsive Nanoparticles for Precise Cancer Therapy

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    Stimuli-responsive nanoparticles with target capacity are of great interest in drug delivery for cancer therapy. However, the challenge is to achieve highly smart release with precise spatiotemporal control for cancer therapy. Herein, we report the preparation and properties of multi-stimuli-responsive nanoparticles through the co-assembly of a 3-arm star quaterpolymer with a near-infrared (NIR) photothermal agent and chemotherapeutic compound. The nanoparticles can exhibit NIR light/pH/reduction–responsive drug release and intracellular drug translocation in cancer cells, which further integrate photoinduced hyperthermia for synergistic anticancer efficiency, thereby leading to tumor ablation without tumor regrowth. Thus, this rational design of nanoparticles with multiple responsiveness represents a versatile strategy to provide smart drug delivery paradigms for cancer therapy

    Light-Responsive Nanoparticles for Highly Efficient Cytoplasmic Delivery of Anticancer Agents

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    Stimuli-responsive nanostructures have shown great promise for intracellular delivery of anticancer compounds. A critical challenge remains in the exploration of stimuli-responsive nanoparticles for fast cytoplasmic delivery. Herein, near-infrared (NIR) light-responsive nanoparticles were rationally designed to generate highly efficient cytoplasmic delivery of anticancer agents for synergistic thermo-chemotherapy. The drug-loaded polymeric nanoparticles of selenium-inserted copolymer (I/D-Se-NPs) were rapidly dissociated in several minutes through reactive oxygen species (ROS)-mediated selenium oxidation upon NIR light exposure, and this irreversible dissociation of I/D-Se-NPs upon such a short irradiation promoted continuous drug release. Moreover, I/D-Se-NPs facilitated cytoplasmic drug translocation through ROS-triggered lysosomal disruption and thus resulted in highly preferable distribution to the nucleus even in 5 min postirradiation, which was further integrated with light-triggered hyperthermia for achieving synergistic tumor ablation without tumor regrowth

    Dually pH/Reduction-Responsive Vesicles for Ultrahigh-Contrast Fluorescence Imaging and Thermo-Chemotherapy-Synergized Tumor Ablation

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    Smart nanocarriers are of particular interest as nanoscale vehicles of imaging and therapeutic agents in the field of theranostics. Herein, we report dually pH/reduction-responsive terpolymeric vesicles with monodispersive size distribution, which are constructed by assembling acetal- and disulfide-functionalized star terpolymer with near-infrared cyanine dye and anticancer drug. The vesicular nanostructure exhibits multiple theranostic features including on-demand drug releases responding to pH/reduction stimuli, enhanced photothermal conversion efficiency of cyanine dye, and efficient drug translocation from lysosomes to cytoplasma, as well as preferable cellular uptakes and biodistribution. These multiple theranostic features result in ultrahigh-contrast fluorescence imaging and thermo-chemotherapy-synergized tumor ablation. The dually stimuli-responsive vesicles represent a versatile theranostic approach for enhanced cancer imaging and therapy

    Multipronged Design of Light-Triggered Nanoparticles To Overcome Cisplatin Resistance for Efficient Ablation of Resistant Tumor

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    Chemotherapeutic drugs frequently encounter multiple drug resistance in the field of cancer therapy. The strategy has been explored with limited success for the ablation of drug-resistant tumor <i>via</i> intravenous administration. In this work, the rationally designed light-triggered nanoparticles with multipronged physicochemical and biological features are developed to overcome cisplatin resistance <i>via</i> the assembly of Pt(IV) prodrug and cyanine dye (Cypate) within the copolymer for efficient ablation of cisplatin-resistant tumor. The micelles exhibit good photostability, sustained release, preferable tumor accumulation, and enhanced cellular uptake with reduced efflux on both A549 cells and resistant A549R cells. Moreover, near-infrared light not only triggers the photothermal effect of the micelles for remarkable photothermal cytotoxicity, but also leads to the intracellular translocation of the micelles and reduction-activable Pt(IV) prodrug into cytoplasm through the lysosomal disruption, as well as the remarkable inhibition on the expression of a drug-efflux transporter, multidrug resistance-associated protein 1 (MRP1) for further reversal of drug resistance of A549R cells. Consequently, the multipronged effects of light-triggered micelles cause synergistic cytotoxicity against both A549 cells and A549R cells, and thus efficient ablation of cisplatin-resistant tumor without regrowth. The multipronged features of light-triggered micelles represent a versatile synergistic approach for the ablation of resistant tumor in the field of cancer therapy

    MnO<sub>2</sub>‑Based Nanoplatform Serves as Drug Vehicle and MRI Contrast Agent for Cancer Theranostics

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    Multidrug resistance (MDR) greatly impedes the therapeutic efficacy of chemotherapeutic agents. Overexpression of ATP-binding cassette (ABC) transporters, such as P-gp, on the surface of tumor cells is a major mechanism in MDR. In this study, we fabricated manganese dioxide (MnO<sub>2</sub>)/doxorubicin (DOX)-loaded albumin nanoparticles (BMDN) for magnetic resonance imaging and reversing MDR in resistant tumor. BMDN facilitated the delivery of DOX into MDR tumor cells through their MDR reversal effects including enhanced cellular uptake, reduced drug efflux, and decreased hypoxic tumor microenvironment. BMDN also acted as an effective MRI contrast agent, thereby causing good in vitro and in vivo <i>T</i><sub>1</sub>-weighted imaging

    Size-Dependent Ag<sub>2</sub>S Nanodots for Second Near-Infrared Fluorescence/Photoacoustics Imaging and Simultaneous Photothermal Therapy

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    Ag<sub>2</sub>S nanoparticles are increasingly important in biomedicine, such as in cancer imaging. However, there has been only limited success in the exploration of theranostic Ag<sub>2</sub>S nanoparticles for photoinduced cancer imaging and simultaneous therapy. Here we report size-dependent Ag<sub>2</sub>S nanodots (NDs) with well-defined nanostructure as a theranostic agent for multimodal imaging and simultaneous photothermal therapy. The NDs are precisely synthesized through carefully controlled growth of Ag<sub>2</sub>S in hollow human serum albumin nanocages. These NDs produce effective fluorescence in second near-infrared (NIR-II) region, distinct photoacoustic intensity, and good photothermal conversion in a size-dependent manner under light irradiation, thereby generating sufficient <i>in vivo</i> fluorescence and photoacoustic signals as well as potent hyperthermia at tumors. Moreover, Ag<sub>2</sub>S NDs possess ideal resistance to photobleaching, effective cellular uptake, preferable tumor accumulation, and <i>in vivo</i> elimination, thus facilitating NIR-II fluorescence/photoacoustics imaging with both ultrasensitivity and microscopic spatial resolution and simultaneous photothermal tumor ablation. These findings provide insight into the clinical potential of Ag<sub>2</sub>S nanodots for cancer theranostics

    Bifunctional Tellurium Nanodots for Photo-Induced Synergistic Cancer Therapy

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    Elemental tellurium (Te) nanoparticles are increasingly important in a variety of applications such as thermoelectricity, photoconductivity, and piezoelectricity. However, they have been explored with limited success in their biomedical use, and thus a tremendous challenge still exists in the exploration of Te nanoparticles that can treat tumors as an effective anticancer agent. Here, we introduce bifunctional Te nanodots with well-defined nanostructure as an effective anticancer agent for photo-induced synergistic cancer therapy with tumor ablation, which is accomplished using hollow albumin nanocages as a nanoreactor. Under near-infrared light irradiation, Te nanodots can produce effective photothermal conversion, as well as highly reactive oxygen species such as •O<sub>2</sub><sup>–</sup> and dismutated •OH <i>via</i> a type-I mechanism through direct electron transfer, thereby triggering the potent <i>in vivo</i> hyperthermia and simultaneous intracellular reactive oxygen species at tumors. Moreover, Te nanodots possess perfect resistance to photobleaching, effective cytoplasmic translocation, preferable tumor accumulation, as well as <i>in vivo</i> renal elimination, promoting severe photo-induced cell damage and subsequent synergy between photothermal and photodynamic treatments for tumor ablation. These findings provide the insight of elemental Te nanodots for biomedical research
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