Complementary autophagy inhibition and glucose metabolism with rattle-structured polydopamine@mesoporous silica nanoparticles for augmented low-temperature photothermal therapy and in vivo photoacoustic imaging.

Rattle-structured nanoparticles with movable cores, porous shells and hollow interiors have shown great effectiveness in drug delivery and cancer theranostics. Targeting autophagy and glucose have provided alternative strategies for cancer intervention therapy. Herein, rattle-structured polydopamine@mesoporous silica nanoparticles were prepared for in vivo photoacoustic (PA) imaging and augmented low-temperature photothermal therapy (PTT) via complementary autophagy inhibition and glucose metabolism. Methods: The multifunctional rattle-structured nanoparticles were designed with the nanocore of PDA and the nanoshell of hollow mesoporous silica (PDA@hm) via a four-step process. PDA@hm was then loaded with autophagy inhibitor chloroquine (CQ) and conjugated with glucose consumer glucose oxidase (GOx) (PDA@hm@CQ@GOx), forming a corona-like structure nanoparticle. Results: The CQ and GOx were loaded into the cavity and decorated onto the surface of PDA@hm, respectively. The GOx-mediated tumor starvation strategy would directly suppress the expression of HSP70 and HSP90, resulting in an enhanced low-temperature PTT induced by PDA nanocore. In addition, autophagy inhibition by the released CQ made up for the loss of low-temperature PTT and starvation efficiencies by PTT- and starvation-activated autophagy, realizing augmented therapy efficacy. Furthermore, the PDA nanocore in the PDA@hm@CQ@GOx could be also used for PA imaging. Conclusion: Such a "drugs" loaded rattle-structured nanoparticle could be used for augmented low-temperature PTT through complementarily regulating glucose metabolism and inhibiting autophagy and in vivo photoacoustic imaging.

Auto-fluorescent polymer nanotheranostics for self-monitoring of cancer therapy via triple-collaborative strategy.

Aberrant regulation of angiogenesis supply sufficient oxygen and nutrients to exacerbate tumor progression and metastasis. Taking this hallmark of cancer into account, reported here is a self-monitoring and triple-collaborative therapy system by auto-fluorescent polymer nanotheranostics which could be concurrently against angiogenesis and tumor cell growth by combining the benefits of anti-angiogenesis, RNA interfere and photothermal therapy (PTT). Auto-fluorescent amphiphilic polymer polyethyleneimine-polylactide (PEI-PLA) with positive charge can simultaneously load hydrophobic antiangiogenesis agent combretastatin A4 (CA4), NIR dye IR825 and absorb negatively charged heat shock protein 70 (HSP70) inhibitor (siRNA against HSP70) to construct self-monitoring nanotheranostics (NPICS). NPICS can effectively restrain the expression of HSP70 to reduce their endurance to the IR825-mediated PTT, leading to an enhanced photocytotoxicity. In a xenograft mouse tumor model, NPICS show an effect of inhibition of tumor angiogenesis and also display a highly synergistic anticancer efficacy with NIR laser irradiation. Significantly, based on its inherent auto-fluorescence, PEI-PLA not only serves as the drug carrier, but also as the self-monitor to real-time track NPICS biodistribution and tumor accumulation via fluorescence imaging. Moreover, IR825 endows NPICS could also be used as photoacoustic (PA) agents for in vivo PA imaging. This nanoplatform shows enormous potentials in cancer theranostics.