A Perfect Pair: Stabilized Black Phosphorous Nanosheets Engineering with Antimicrobial Peptides for Robust Multidrug Resistant Bacteria Eradication.

Black phosphorus (BP) nanosheets emerged as promising 2D nanomaterial that have been applied to eradicate antibiotic-resistant bacteria. However, their applications are limited by intrinsic ambient instability. Here, the ε-poly-l-lysine (ε-PL)-engineered BP nanosheets are constructed via simple electrostatic interaction to cater the demand for passivating BP with amplified antibacterial activity. The dual drug-delivery complex named BP@ε-PL can closely anchor onto the surface of bacteria, leading to membrane disintegration. Subsequently, in situ hyperthermia generated by BP under near-infrared (NIR) irradiation can precisely eradicate pathogenic bacteria. In vitro antibacterial studies verify the rapid disinfection ability of BP@ε-PL against Methicillin-resistant Staphylococcus aureus (MRSA) within 15 min. Moreover, ε-PL can serve as an effective protector to avoid chemical degradation of bare BP. The in vivo antibacterial study shows that a 99.4% antibacterial rate in a MRSA skin infection model is achieved, which is accompanied by negligible toxicity. In conclusion, this work not merely provides a new conjecture for protecting the BP, but also opens a novel window for synergistic antibiotic-resistant bacteria therapy based on antimicrobial peptides and 2D photothermal nanomaterial.

Intelligent and spatiotemporal drug release based on multifunctional nanoparticle-integrated dissolving microneedle system for synergetic chemo-photothermal therapy to eradicate melanoma.

Cutaneous melanoma is one of the most common malignant skin cancer with high lethality. Chemotherapy and photothermal therapy are important and extensively studied treatment modalities for melanoma. However, these therapies still face some challenges, which severely restrict their further applications, such as unsatisfactory efficacy of monotherapy, nonspecific uptake and release during drug delivery, and unexpected adverse effects from system administration. Recently, the strategies of collaboration, functional modification, stimuli-responsive design, and topical administration all show great prospect for solving above problems. In this research, a multifunctional nanoparticle-integrated dissolving microneedle drug delivery system was constructed, in which the nanoparticles were prepared based on the framework with the incorporation of photothermal agent (CuS) into Zeolitic imidazolate framework-8 and functionalized by hyaluronic acid. This system can co-load multi-modal drugs, improve specific uptake and distribution of targeted tumor, deliver drug locally, and release drug intelligently and spatiotemporally, thereby promising a low-dose administration with high efficiency. The high inhibiting tumor performance and excellent systematic safety were verified both in vitro and in vivo. Together, this smart design overcame the drawbacks of monotherapy and conventional system administration. We believe the nanoparticle-integrated dissolving microneedles will be in prospect of clinical application for more superficial tumors with further delicate optimization. STATEMENT OF SIGNIFICANCE: Melanoma is one of the most common skin cancers with high lethality. Extensively studied chemotherapy and photothermal therapy still face some challenges, such as the limited therapeutic efficacy and the severe system adverse effects. In order to overcome these drawbacks, the multifunctional nanoparticle-integrated dissolving microneedles (DMNs) were designed. Especially, the nanoparticles could co-load multi-modal drugs, improve specific uptake, and release drug intelligently and spatiotemporally. The microneedles could increase the drug accumulation in tumor, thus achieving excellent therapeutic efficacy and reducing side effects. This system paved the way to a less invasive, more focused and efficient therapeutic strategy for melanoma therapy.

The rough inhalable ciprofloxacin hydrochloride microparticles based on silk fibroin for non-cystic fibrosis bronchiectasis therapy with good biocompatibility.

Non-cystic fibrosis bronchiectasis (NCFB) is a chronic respiratory disease, and the thick and viscous mucus covering on respiratory epithelia can entrap the inhaled drugs, resulting in compromised therapeutic efficiency. In order to solve this problem, the inhalable ciprofloxacin hydrochloride microparticles (CMs) based on silk fibroin (SF) and mannitol (MAN) were designed and developed. SF was applied to increase the loading efficiency of ciprofloxacin hydrochloride by strong electrostatic interactions. MAN could facilitate the penetration of drugs through mucus, which ensured the drugs could reach their targets before clearance. Furthermore, the aerodynamic performance of the inhalable microparticles could be tuned by changing the surface roughness to achieve a high fine particle fraction value (45.04%). The antibacterial effects of CMs were also confirmed by measuring the minimum inhibitory concentration against four different bacteria strains. Moreover, a series of experiments both in vitro and in vivo showed that CMs would not affect the lung function and induce the secretion of inflammatory cytokines in lungs, demonstrating their excellent biocompatibility and biosafety. Therefore, CMs might be a promising pulmonary drug delivery system for the treatment of NCFB.