Near-Infrared Plasmon-Boosted Heat/Oxygen Enrichment for Reversing Rheumatoid Arthritis with Metal/Semiconductor Composites.

Rheumatoid arthritis (RA) is an autoimmune disease that often causes progressive joint dysfunction, even disability and death in severe cases. The radical improvement of inflammatory cell infiltration and the resulting disorder in oxygen supply is a novel therapeutic direction for RA. Herein, a near-infrared-absorbing metal/semiconductor composite, polyethylene glycol-modified ceria-shell-coated gold nanorod (Au@CeO2), is fabricated for topical photothermal/oxygen-enriched combination therapy for RA in a mouse model. Upon laser irradiation, the photothermal conversion of Au@CeO2 is exponentially enhanced by the localized surface plasma resonance-induced light focusing. The elevated temperature can not only remarkably obliterate hyperproliferative inflammatory cells gathered in diseased joints but also vastly increase the catalase-like activity of ceria to accelerate the decomposition of H2O2 to produce much oxygen, which relieves hypoxia. Significantly, RA-induced lesions are improved, and the expression of proinflammatory cytokines and hypoxia-inducible factors is effectively repressed under the cooperation of heat and oxygen. Overall, the core/shell-structured Au@CeO2 is a promising nanotherapeutic platform that can well realize light-driven heat/oxygen enrichment to completely cure RA from the perspective of pathogenesis.

Versatile pH-response Micelles with High Cell-Penetrating Helical Diblock Copolymers for Photoacoustic Imaging Guided Synergistic Chemo-Photothermal Therapy.

With high optical absorption efficiency, near infrared (NIR) dyes have been proposed as theranostic agents for fluorescence imaging, photoacoustic imaging (PAI), and photothermal therapy (PTT). However, inherent hydrophobicity and short circulation time of small molecule hinder the further biomedical application. Herein smart amphiphilic copolymer was synthesized containing IR780/camptothecin@poly(ε-caprolactone) (IR780/CPT@PCL) as core, helical poly(phenyl isocyanide) (PPI) blocks as shell with the pH-responsive rhodamine B (RhB) moieties in the core-shell interface. With hydrophilic helical PPI coronas, these micelles present significantly enhanced cell-penetrating capacity that plays a key role in facilitating intracellular delivery of various cargos. By encapsulating CPT and IR780 molecules, the multifunctional self-assemble probe has huge potential to realize functional cooperativity and adaptability for cancer diagnosis and therapy. The in vitro and in vivo experimental results demonstrate that the pH-triggered fluorescent responsiveness and strong acoustic generation permit them efficient fluorescent and PA signal sensing for cancer diagnosis. Moreover, with 808 nm laser irradiation, the generated heat significantly improves the drug release from PCL core, leading to synergetic chemo-photothermal therapy and decreases tumor recurrence rates in mice. Overall, the biocompatible multifunctional micelles with these combined advantages can potentially be utilized for PAI guided disease diagnosis and tumor ablation.

Photosensitizer loaded nano-graphene for multimodality imaging guided tumor photodynamic therapy.

Graphene, a 2-dimensional carbon nanomaterial, has attracted wide attention in biomedical applications, owing to its intrinsic physical and chemical properties. In this work, a photosensitizer molecule, 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-alpha (HPPH or Photochlor®), is loaded onto polyethylene glycol (PEG)-functionalized graphene oxide (GO) via supramolecular π-π stacking. The obtained GO-PEG-HPPH complex shows high HPPH loading efficiency. The in vivo distribution and delivery were tracked by fluorescence imaging as well as positron emission tomography (PET) after radiolabeling of HPPH with (64)Cu. Compared with free HPPH, GO-PEG-HPPH offers dramatically improved photodynamic cancer cell killing efficacy due to the increased tumor delivery of HPPH. Our study identifies a role for graphene as a carrier of PDT agents to improve PDT efficacy and increase long-term survival following treatment.

Dual-factor triggered fluorogenic nanoprobe for ultrahigh contrast and subdiffraction fluorescence imaging.

Ultrahigh contrast fluorescence molecular imaging has long been pursued over the past few decades from basic sciences to clinics. Although new classes of near-infrared (NIR) molecular probes are emerging, the requirement of fluorophores with high quantum yield, high signal to noise (S/N) ratio, and being activatable to microenvironment changes can hardly be fulfilled. In this study, a new NIR dye embedded fluorogenic nanoprobe (fg-nanoprobe) was developed for ultrahigh contrast in vitro and in vivo imaging with negligible background interference. The achieved S/N ratio was found to be attributed to the synergistic effects of the cellular compartmental triggered fluorogenicity and pH tunable fluorescence on/off character. In addition, this constructed fluorogenic nanoprobe could be coupled with image processing method for super-resolution subdiffraction imaging. The developed fg-nanoprobe integrated photophysical merits of the synthesized NIR fluorophore and advantages of engineered nanoparticle for enhanced fluorescence molecular imaging. This probe may open another avenue for ultrahigh contrast fluorescence molecular imaging in the future.