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

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

Bacteria-Activated Theranostic Nanoprobes against Methicillin-Resistant <i>Staphylococcus aureus</i> Infection

Despite numerous advanced imaging and sterilization techniques available nowadays, the sensitive <i>in vivo</i> diagnosis and complete elimination of drug-resistant bacterial infections remain big challenges. Here we report a strategy to design activatable theranostic nanoprobes against methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) infections. This probe is based on silica nanoparticles coated with vancomycin-modified polyelectrolyte-cypate complexes (SiO₂-Cy-Van), which is activated by an interesting phenomenon of bacteria-responsive dissociation of the polyelectrolyte from silica nanoparticles. Due to the aggregation of hydrophobic cypate fluorophores on silica nanoparticles to induce ground-state quenching, the SiO₂-Cy-Van nanoprobes are nonfluorescent in aqueous environments. We demonstrate that MRSA can effectively pull out the vancomycin-modified polyelectrolyte-cypate complexes from silica nanoparticles and draw them onto their own surface, changing the state of cypate from off (aggregation) to on (disaggregation) and leading to <i>in vitro</i> MRSA-activated near-infrared fluorescence (NIRF) and photothermal elimination involving bacterial cell wall and membrane disruption. <i>In vivo</i> experiments show that this <i>de novo</i>-designed nanoprobe can selectively enable rapid (4 h postinjection) NIRF imaging with high sensitivity (10⁵ colony-forming units) and efficient photothermal therapy (PTT) of MRSA infections in mice. Remarkably, the SiO₂-Cy-Van nano­probes can also afford a long-term tracking (16 days) of the development of MRSA infections, allowing real-time estimation of bacterial load in infected tissues and further providing a possible way to monitor the efficacy of antimicrobial treatment. The strategy of bacteria-activated polyelectrolyte dissociation from nanoparticles proposed in this work could also be used as a general method for the design and fabrication of bacteria-responsive functional nanomaterials that offer possibilities to combat drug-resistant bacterial infections

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

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