In Situ Sprayed Biotherapeutic Gel Containing Stable Microbial Communities for Efficient Anti-Infection Treatment.

Systematic administration of antibiotics to treat infections often leads to the rapid evolution and spread of multidrug-resistant bacteria. Here, an in situ-formed biotherapeutic gel that controls multidrug-resistant bacterial infections and accelerates wound healing is reported. This biotherapeutic gel is constructed by incorporating stable microbial communities (kombucha) capable of producing antimicrobial substances and organic acids into thermosensitive Pluronic F127 (polyethylene-polypropylene glycol) solutions. Furthermore, it is found that the stable microbial communities-based biotherapeutic gel possesses a broad antimicrobial spectrum and strong antibacterial effects in diverse pathogenic bacteria-derived xenograft infection models, as well as in patient-derived multidrug-resistant bacterial xenograft infection models. The biotherapeutic gel system considerably outperforms the commercial broad-spectrum antibacterial gel (0.1% polyaminopropyl biguanide) in pathogen removal and infected wound healing. Collectively, this biotherapeutic strategy of exploiting stable symbiotic consortiums to repel pathogens provides a paradigm for developing efficient antibacterial biomaterials and overcomes the failure of antibiotics to treat multidrug-resistant bacterial infections.

Peptide-based semiconducting polymer nanoparticles for osteosarcoma-targeted NIR-II fluorescence/NIR-I photoacoustic dual-model imaging and photothermal/photodynamic therapies.

BACKGROUND: The overall survival rate of osteosarcoma (OS) patients has not been improved for 30 years, and the diagnosis and treatment of OS is still a critical issue. To improve OS treatment and prognosis, novel kinds of theranostic modalities are required. Molecular optical imaging and phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT), are promising strategies for cancer theranostics that exhibit high imaging sensitivity as well as favorable therapeutic efficacy with minimal side effect. In this study, semiconducting polymer nanoparticles (SPN-PT) for OS-targeted PTT/PDT are designed and prepared, using a semiconducting polymer (PCPDTBT), providing fluorescent emission in the second near-infrared window (NIR-II, 1000 - 1700 nm) and photoacoustic (PA) signal in the first near-infrared window (NIR-I, 650 - 900 nm), served as the photosensitizer, and a polyethylene glycolylated (PEGylated) peptide PT, providing targeting ability to OS. RESULTS: The results showed that SPN-PT nanoparticles significantly accelerated OS-specific cellular uptake and enhanced therapeutic efficiency of PTT and PDT effects in OS cell lines and xenograft mouse models. SPN-PT carried out significant anti-tumor activities against OS both in vitro and in vivo. CONCLUSIONS: Peptide-based semiconducting polymer nanoparticles permit efficient NIR-II fluorescence/NIR-I PA dual-modal imaging and targeted PTT/PDT for OS.

The Effect and Mechanism of Negative Pressure Wound Therapy on Lymphatic Leakage in Rabbits.

BACKGROUND: Lymphatic leakage is one of the severe complications after lymphadenectomy. However, efficient treatment it still unclear. MATERIALS AND METHODS: We employed inguinal lymphadenectomy and saphenous lymphatic vessel excision to establish a inguinal lymphatic leakage rabbit model. Rabbits with bilateral lymphatic leakage were divided in two groups, which were subject to negative pressure wound therapy (NPWT) on right sides and dressing change on left sides, respectively. Following 7-11 d of treatment, skin thickness and drainage volume were measured. Western blot and RT-PCR were used for analyzing the VEGF-C level. Tissues of wound were dissected and subject to anti-LYVE-1 immunohistochemical for lymphatic average positive staining area percentage and the ratio of lymphatic lumen area evaluation. RESULTS: Our lymphatic leakage model showed significant lymph stasis, delayed wound healing, and skin swelling and was confirmed by methylene blue instillation. Using this rabbit model, we found that NPWT could largely promote wound healing and resolution of skin edema. Compared with the dressing change group, the thickness of the dermis layer in the NPWT group was significantly reduced. Western blot and RT-PCR analysis showed a decrease of VEGF-C in the NPWT group. The immunohistochemical result of the NPWT group did not show a significant change in lymphatic average positive staining area percentage, whereas the ratio of lymphatic lumen area was significantly decreased, suggesting that NPWT treatment can significantly compress the dilated lymphatic vessels. CONCLUSIONS: We successfully established the first clinically relevant lymphatic leakage model in rabbits. NPWT can be an effective treatment for lymphatic leakage via reducing edema and lymphatic stasis by compressing dilated lymph vessels and promoting lymphatic drainage.

Efficacy of thermosensitive chitosan/ß-glycerophosphate hydrogel loaded with ß-cyclodextrin-curcumin for the treatment of cutaneous wound infection in rats.

Wound infection has been a persistent problem that is common and costly. Thermosensitive hydrogel has been demonstrated to be a suitable dressing candidate due to its high moldability, easy administration and ability to maintain a moist topical environment at the wound bed. In the present study, a novel thermosensitive hydrogel was successfully prepared and characterized to have a porous inner structure and a sustained curcumin-releasing profile. The wound healing ability of the hydrogel was investigated in a wound infection model in rats. On analysis, it was observed that the hydrogel complex-dressed wounds exhibited a faster wound closure rate compared with gauze-covered wounds, which was paralleled with improved histological outcomes that were observed. Additionally, the results of in vitro antimicrobial, anti-oxidant, western blot analysis and reverse transcription-quantitative polymerase chain reaction assays indicated that the hydrogel complex had distinct anti-oxidative, antimicrobial and anti-nuclear factor-κB-signaling capacities. These results suggest that this novel hydrogel may be a suitable candidate for facilitating the healing of infected cutaneous wounds in rats.

Co-targeting of DNA, RNA, and protein molecules provides optimal outcomes for treating osteosarcoma and pulmonary metastasis in spontaneous and experimental metastasis mouse models.

Metastasis is a major cause of mortality for cancer patients and remains as the greatest challenge in cancer therapy. Driven by multiple factors, metastasis may not be controlled by the inhibition of single target. This study was aimed at assessing the hypothesis that drugs could be rationally combined to co-target critical DNA, RNA and protein molecules to achieve "saturation attack" against metastasis. Independent actions of the model drugs DNA-intercalating doxorubicin, RNA-interfering miR-34a and protein-inhibiting sorafenib on DNA replication, RNA translation and protein kinase signaling in highly metastatic, human osteosarcoma 143B cells were demonstrated by the increase of γH2A.X foci formation, reduction of c-MET expression and inhibition of Erk1/2 phosphorylation, respectively, and optimal effects were found for triple-drug combination. Consequently, triple-drug treatment showed a strong synergism in suppressing 143B cell proliferation and the greatest effects in reducing cell invasion. Compared to single- and dual-drug treatment, triple-drug therapy suppressed pulmonary metastases and orthotopic osteosarcoma progression to significantly greater degrees in orthotopic osteosarcoma xenograft/spontaneous metastases mouse models, while none showed significant toxicity. In addition, triple-drug therapy improved the overall survival to the greatest extent in experimental metastases mouse models. These findings demonstrate co-targeting of DNA, RNA and protein molecules as a novel therapeutic strategy for the treatment of metastasis.

Ligustilide treatment promotes functional recovery in a rat model of spinal cord injury via preventing ROS production.

Ligustilide from traditional Chinese medicine extract, angelica sinensis is one of the main active components, and has many pharmacological activities related to the effectiveness. This study sought to determine whether neuro-protection of ligustilide promotes functional recovery in a rat model of spinal cord injury (SCI) via preventing ROS production. Male Sprague-Dawley (SD) rats were induced using operation for model SCI. Furthermore, Basso, Beattie, Bresnahan (BBB) scale and footprint analysis of gait was used to assess the neuro-protection of ligustilide on SCI. The intracellular reactive oxygen species (iROS), prostaglandin E(2) (PGE(2)), interleukin-1ß (IL-1ß) and tumor necrosis factor (TNF)-α production levels were measured by monoclonal enzyme immunoassay kit. Inducible nitric oxide synthase (iNOS) gene expression, activator protein-1 (AP-1) and c-Jun N-terminal kinase (JNK) protein expressions were detected using Quantitative real-time reverse transcription polymerase chain reaction (Q-PCR) and western blot analyses, respectively. Interestingly, treatment with ligustilide significantly increased BBB scale and reduced recovery of coordination in SCI rats. After SCI, the iROS, PGE(2), IL-1ß, TNF-α production levels and iNOS gene expression were significantly suppressed in SCI rats. These results suggest that the neuro-protection of ligustilide promotes functional recovery in a rat model of spinal cord injury via preventing ROS production.