Ultra-thin silica shell-guarded nanoflares for high-fidelity live cell miRNA-21 imaging by fully avoiding the interference of biothiols.

We successfully constructed a new class of nanoflares based on ultra-thin silica-coated gold nanoparticles (Au@SiO2) with the covalent binding of nucleic acids, which demonstrated more resistance to biothiols than that exhibited in the traditional Au-S binding strategy, for imaging the target miRNA-21 with high fidelity in living cells.

Near-infrared-guided NO generator for combined NO/photothermal/chemodynamic therapy of bacterial infections.

Nitric oxide (NO)-based gas therapy approaches are promising in the treatment of infections; however, these strategies are hindered by poor delivery to the target site, which leads to unsatisfactory effects. In this study, we developed a NO-controlled platform (SCM@HA) via NO-generating mesoporous silica nanoparticles co-doped with sodium nitroprusside and copper sulphide to control NO production under near-infrared (NIR)-laser irradiation. Irradiation with an 808 nm NIR laser rapidly triggered the release of NO from the particles to actualise gas therapy. Photothermal therapy (PTT) also increased the local microenvironment temperature, and the close relationship between chemodynamic therapy (CDT) and temperature suggests that the increasing temperature facilitates in its working. The hydroxyl radicals generated by CDT can destroy the structure of bacteria in acidic environments. The germicidal activity of the nanoparticles was determined by the combined action of PTT, CDT, and NO-based gas therapy. The nanoparticles showed bactericidal activity in vitro against bacterial strains Staphylococcus aureus (S. aureus) and Salmonella typhimurium (S. typhimurium). Finally, the anti-infective efficacy in vivo in S. aureus-infected mouse model was demonstrated. Thus, the synergistic antimicrobial effects of NO-generating silica nanoparticles have good potential for the non-antibiotic treatment of bacterial infections in wounds. STATEMENT OF SIGNIFICANCE: Bacterial infections and resistance are challenging health threats. Therefore, the development of an antibiotic-independent method is essential for the treatment of wound bacterial infections. In this study, NO-generating nanoparticles loaded with sodium nitroprusside in copper sulphide-doped mesoporous silica were prepared to control the long-term release of NO using near-infrared laser, which has good efficacy of PTT and CDT. The bactericidal effects of as-prepared nanoparticles against S. aureus and S. typhimurium have been well elucidated. This study proposes a feasible method in the field of NO-based therapy, thus paving the way that will benefit for the treatment of bacterial infections in wounds.

Acidic biofilm microenvironment-responsive ROS generation via a protein nanoassembly with hypoxia-relieving and GSH-depleting capabilities for efficient elimination of biofilm bacteria.

Reactive oxygen species (ROS) are widely considered to the effective therapeutics for fighting bacterial infections especially those associated with biofilm. However, biofilm microenvironments including hypoxia, limited H2O2, and high glutathione (GSH) level seriously limit the therapeutic efficacy of ROS-based strategies. Herein, we have developed an acidic biofilm microenvironment-responsive antibacterial nanoplatform consisting of copper-dopped bovine serum albumin (CBSA) loaded with copper peroxide (CuO2) synthesized in situ and indocyanine green (ICG). The three-in-one nanotherapeutics (CuO2/ICG@CBSA) are capable of releasing Cu2+ and H2O2 in a slightly acidic environment, where Cu2+ catalyzes the conversion of H2O2 into hydroxyl radical (•OH) and consumes the highly expressed GSH to disrupt the redox homeostasis. With the assistance of an 808 nm laser, the loaded ICG not only triggers the production of singlet oxygen (1O2) by a photodynamic process, but also provides photonic hyperpyrexia that further promotes the Fenton-like reaction for enhancing •OH production and induces thermal decomposition of CuO2 for the O2-self-supplying 1O2 generation. The CuO2/ICG@CBSA with laser irradiation demonstrates photothermal-augmented multi-mode synergistic bactericidal effect and is capable of inhibiting biofilm formation and eradicating the biofilm bacteria. Further in vivo experiments suggest that the CuO2/ICG@CBSA can effectively eliminate wound infections and accelerate wound healing. The proposed three-in-one nanotherapeutics with O2/H2O2-self-supplied ROS generating capability show great potential in treating biofilm-associated bacterial infections. STATEMENT OF SIGNIFICANCE: Here, we have developed an acidic biofilm microenvironment-responsive nanoplatform consisting of copper-dopped bovine serum albumin (CBSA) loaded with copper peroxide (CuO2) synthesized in situ and indocyanine green (ICG). The nanotherapeutics (CuO2/ICG@CBSA) are capable of releasing Cu2+ and H2O2 in an acidic environment, where Cu2+ catalyzes the conversion of H2O2 into •OH and consumes the overexpressed GSH to improve oxidative stress. With the aid of an 808 nm laser, ICG provides photonic hyperpyrexia for enhancing •OH production, and triggers O2-self-supplying 1O2 generation. CuO2/ICG@CBSA with laser irradiation displays photothermal-augmented multi-mode antibacterial and antibiofilm effect. Further in vivo experiments prove that CuO2/ICG@CBSA effectively eliminates wound infection and promotes wound healing. The proposed three-in-one nanotherapeutics show great potential in treating biofilm-associated bacterial infections.