Ofloxacin-loaded HMPB NPs for Klebsiella pneumoniae eradication in the surgical wound with the combination of PTT.

Klebsiella pneumoniae (K. pneumoniae) is a common bacterium whose drug-resistant can cause surgical failures and incurable infections in hospital patients. Thus, how to reverse or delay the resistance induction has become a great challenge for development antiresistant drug. Recently, the combination of nanomaterial-loaded antibiotics with photothermal therapy showed the efficient antibacteria ability under a low dosage of antibiotics. In this study, a nanocomposite of HMPB NPs with inherent photothermal therapy capability was used to eradicate K. pneumoniae after loading with Ofloxacin, an antibiotic against K. pneumoniae in vitro and in vivo. The nanocomplexes named as Ofloxacin@HMPB@HA NPs showed a higher effect against K. pneumoniae by destroying cell integrity and inducing ATP leakage with the assistance of laser irradiation, compared with sole Ofloxacin@HMPB@HA NPs or laser irradiation. Surgical wound infection assay further demonstrated the efficient killing K. pneumoniae and promoting the formation of new tissues, as well, which was reflected by the rapid healing of surgical wound. In summary, these results indicate the great potential of this combinational tactic based on Ofloxacin@HMPB@HA NPs for preventing the failure caused by K. pneumoniae infection.

Near-infrared laser-assisted Ag@Chi-PB nanocompounds for synergistically eradicating multidrug-resistant bacteria and promoting diabetic abscess healing.

Chronic wound infections, particularly multidrug-resistant microbe-caused infections, have imposed severe challenges in clinical administration. The therapeutic effectiveness of the current strategy using conventional antibiotics is extremely unsatisfactory. The development of novel treatment strategies to inhibit the infections caused by multidrug-resistant bacteria is highly desired. In this work, based on the combination of nanocompounds with the assistance of NIR laser, an antibacterial strategy was designed for MRSA-infected abscesses in diabetic mice. The nanocompounds named Ag@Chi-PB were prepared by using chitosan-coated Prussian blue (PB) as a nanocarrier for silver nanoparticles anchoring. Combined with near-infrared (NIR) laser, the nanocompounds were more efficient at killing Escherichia coli (E. coli) and Methicillin-resistant staphyllococcus aureus (MRSA) in vitro. Notably, MRSA was significantly removed in vivo and promoted diabetic abscess healing by the combined therapy of this nanocompound and NIR laser, owing to the synergistic antibacterial effect of photothermal therapy and release of Ag+. Meanwhile, the nanocompound showed satisfactory biocompatibility and superior biosafety. Collectively, the combination therapy of this nanocompound with the assistance of NIR laser may represent a promising strategy for clinical anti-infection.

Real-time tracking of the intracellular delivery of a 2D nanosystem using a progressively activatable fluorescence platform for cancer diagnosis.

In this work, a smart nanoplatform responding to multiple biomarkers has been developed for the real-time tracking of the intracellular delivery of a 2D nanosystem. Our work provides a promising avenue for developing an optimized imaging nanoplatform for site-specific imaging and real-time tracking of the delivery process.

Nongenetic surface engineering of mesenchymal stromal cells with polyvalent antibodies to enhance targeting efficiency.

Systemic infusion is a prevalent administration method for mesenchymal stromal cells (MSCs) in clinical trials. However, the inability to deliver a large number of therapeutic cells to diseased tissue is a substantial barrier. Here, we demonstrate that surface engineering of MSCs with polyvalent antibodies can effectively improve the targeting efficiency of MSCs to diseased tissue. The polyvalent antibody is directly synthesized on the cell surface via DNA template-directed biomolecule assembly. The data show that engineered MSCs exhibit superior adhesion to inflamed endothelium in vitro and in vivo. In female mouse models of acute inflammation and inflammatory bowel disease, engineered MSCs show enhanced targeting efficiency and therapeutic efficacy in damaged tissues. Notably, the entire procedure for polyvalent functionalization only requires the simple mixing of cells and solutions under physiological conditions within a few hours, which significantly reduces preparation processes and manufacturing costs and minimizes the impact on the cells. Thus, our study provides a strategy for improved MSC-based regenerative medicine.

Silver nanoparticles coated by green graphene quantum dots for accelerating the healing of MRSA-infected wounds.

Bacterial infection, especially multidrug-resistant bacteria-induced infection, threatens human health seriously, which has posed great challenges for clinical therapy. The overuse of conventional antibiotics has given rise to bacterial resistance that severely restricts the clinical treatment options of conventional antibiotics. The development of highly effective antibacterial materials and therapeutic strategies to inhibit the multidrug-resistant bacteria-induced infections is of great urgency. Although silver nanoparticles (AgNPs) have exhibited certain effectiveness in killing multidrug-resistant bacteria, their antibacterial efficacy and biosafety are still unsatisfactory. In this work, we prepared graphene quantum dots (GQDs) by a green synthesis method with the natural polymer starch as a precursor for uniformly decorating AgNPs to form GQDs coated AgNPs (GQDs@Ag). The nanocomplex was comprehensively characterized, and its antibacterial activity and biosafety were systematically investigated. The characterization results revealed that the successfully constructed GQDs@Ag hybrids with improved dispersion and stability are composed of AgNPs closely and uniformly surrounded by the GQDs. Furthermore, in vitro and in vivo results demonstrated that GQDs@Ag hybrids with superior biosafety showed a markedly enhanced effect in killing MRSA and accelerating MRSA-infected wound healing as compared to AgNPs alone. Collectively, these results suggest that the biocompatible nanosystem of GQDs@Ag exhibits great potential in clinical application for MRSA infection.

PB@PDA@Ag nanosystem for synergistically eradicating MRSA and accelerating diabetic wound healing assisted with laser irradiation.

The ever-growing threats of multidrug-resistant bacterial infection and chronic wound healing have created an imperative need for the development of novel antibacterial materials and therapeutic strategies, especially for diabetic patients infected with multidrug-resistant bacteria. In this work, the nanocomplexes named as PB@PDA@Ag were used for eradicating multidrug-resistant bacteria and accelerating wound healing of MRSA-infected diabetic model with the assistance of laser irradiation. In vitro results revealed that the combinational strategy exerted a synergistic effect for anti-MRSA through disrupting cell integrity, producing ROS, declining ATP, and oxidizing GSH, comparing with PB@PDA@Ag or NIR laser irradiation alone. Moreover, in vivo assay demonstrated that this system effectively accelerated MRSA-infected diabetic wound healing by mitigating local inflammatory response and up-regulating VEGF expression on the wound bed. Meanwhile, satisfactory biocompatibility and negligible damage to major organs were observed. Altogether, the aforementioned results indicate that the combinational therapy of PB@PDA@Ag and NIR irradiation shows a great potential application in the field of clinic infection.

Daptomycin and AgNP co-loaded rGO nanocomposites for specific treatment of Gram-positive bacterial infection in vitro and in vivo.

In order to improve the stability of AgNPs and decrease the dosage of Daptomycin for killing bacteria, a reduced graphene oxide (rGO) was used for simultaneously anchoring AgNPs and Daptomycin to prepare rGO@Ag@Dap nanocomposites. In vitro experiments showed that the nanocomposites can efficiently kill four kinds of pathogenic bacteria, especially two kinds of Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis) through damaging cell integrity, producing ROS, decreasing ATP and GSH and disrupting bacterial metabolism. Against Gram-positive bacteria, the rGO@Ag@Dap nanocomposites showed a cooperative antibacterial effect. Moreover, in vivo experiments showed that rGO@Ag@Dap can improve the healing of wounds infected with bacteria by efficiently killing the bacteria on the wounds and further promoting skin regeneration and dense collagen deposition. In summary, the above results suggest that the cooperative function of AgNPs with Daptomycin can significantly improve antibacterial efficiency against infectious diseases caused by bacteria, especially for therapies made ineffective due to the drug resistance of pathogenic bacteria.