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Hypertrophic scarring (HS) is a common skin injury complication with unmet needs. Verteporfin (VP) should be an ideal HS-targeted therapeutic drug due to its efficient fibrosis and angiogenesis inhibitory abilities. However, its application is restricted by its side effects such as dose-dependent cytotoxicity on normal cells. Herein, the bioadhesive nanoparticles encapsulated VP (VP/BNPs) are successfully developed to attenuate the side effects of VP and enhance its HS inhibition effects by limiting VP releasing slowly and stably in the lesion site but not diffusing easily to normal tissues. VP/BNPs displayed significant inhibition on the proliferation, migration, collagen deposition, and vessel formation of human hypertrophic scar fibroblasts (HSFBs) and dermal vascular endothelial cells (HDVECs). In a rat tail HS model, VP/BNPs treated HS exhibits dramatic scar repression with almost no side effects compared with free VP or VP-loaded non-bioadhesive nanoparticles (VP/NNPs) administration. Further immunofluorescence analysis on scar tissue serial sections validated VP/BNPs effectively inhibited the collagen deposition and angiogenesis by firmly confined in the scar tissue and persistently releasing VP targeted to nucleus Yes-associated protein (nYAP) of HSFBs and HDVECs. These findings collectively suggest that VP/BNPs can be a promising and technically advantageous agent for HS therapies., (© 2023 Wiley‐VCH GmbH.)

To identify a replacement strategy for bronchial thermoplasty (BT) with non-invasive and free-of-severe side effect is urgently needed in the clinic for severe asthma treatment. In this study, PLGA-PEG@ICG@TRPV1 pAb (PIT) photothermal nanoparticles targeting bronchial TRPV1 were designed for photothermal therapy (PTT) against severe murine asthma induced by ovalbumin and lipopolysaccharide. PIT was formulated with a polyethylene glycol (PEG)-grafted poly (lactic-co-glycolic) acid (PLGA) coating as a skeleton structure to encapsulate indocyanine green (ICG) and was conjugated to the polyclonal antibody against transient receptor potential vanilloid 1 (TRPV1 pAb). The results revealed that PIT held good druggability due to its electronegativity and small diameter. PIT demonstrated great photothermal effects both in vivo and in vitro and exhibited good ability to target TRPV1 in vitro because of its selective cell uptake and specific cell toxicity toward TRPV1-overexpressing cells. The PIT treatment effectively reduced asthma symptoms in mice. This is evident from improvements in expiratory airflow limitation, significant decreases in inflammatory cell infiltration in the airways, and increases in goblet cell and columnar epithelial cell proliferation. In conclusion, PIT alleviates severe murine asthma symptoms through a combination of TRPV1 targeting and photothermal effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ocular formulations should provide an effective antibiotic concentration at the site of infection to treat bacterial eye infections. However, tears and frequent blinking accelerate the drug clearance rate and limit drug residence time on the ocular surface. This study describes a biological adhesion reticulate structure (BNP/CA-PEG) consisting of antibiotic-loaded bioadhesion nanoparticles (BNP/CA), with an average 500-600 nm diameter, and eight-arm NH 2 -PEG-NH 2 for local and extended ocular drug delivery. This retention-prolonging effect is a function of the Schiff base reaction between groups on the surface of BNP and amidogen on PEG. BNP/CA-PEG showed significantly higher adhesion properties and better treatment efficacy in an ocular rat model with conjunctivitis in comparison to non-adhesive nanoparticles, BNP, or free antibiotics. Both in vivo safety experiment and in vitro cytotoxicity test verified the biocompatibility and biosafety of the biological adhesion reticulate structure, indicating a promising translational prospect for further clinical use.

Fenton reaction-based chemodynamic therapy is hardly a self-sufficient cancer treatment, due to its stringent reaction conditions, limited substrate concentration, and negative feedback from the tumor microenvironment. Herein, we synthesized a novel two-dimensional (2D) vanadium-based nanosheets (Vanadene, V NSs) with polyvalent surfaces (V IV /V V ), a very narrow band gap of 0.8 eV, and high biodegradability by a liquid-phase exfoliation strategy. The polyvalent surface endowed its multiple capabilities to modulate TME through GSH consumption and O 2 production via V V and to catalyze a Fenton-like reaction to produce ·OH under a mild condition via V IV . In addition, efficient energy conversions including near-infrared (NIR)-thermal conversion (photothermal therapy, PTT) and NIR-electron conversion (photodynamic therapy, PDT) were ensured by the narrow band gap, in which NIR-thermal conversion enhanced the Fenton-like reaction activity through accelerating ionization while NIR-electron conversion catalyzed the conversion of O 2 to ·O 2 - for further breaking redox homeostasis. Moreover, V NSs-based nanocatalyst can be slowly degraded into non-toxic species, enabling it to be innocuously eliminated from the body after completing tumor eradication by single drug injection and single NIR irradiation. Therefore, this study provides new insights into a universal nanoplatform for NIR-enhanced combination cancer therapy, highlighting the utility of 2D V NSs in the field of biomedicine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The effective treatment of esophageal disease represents a significant unmet clinical need, as existing treatments often lead to unnecessary systemic drug exposure and suboptimal concentrations at the disease site. Here, surface-modified bioadhesive poly(lactic acid)-hyperbranched polyglycerol nanoparticles (BNPs), with an average 100-200 nm diameter, were developed for local and sustained esophageal drug delivery. BNPs showed significantly higher adhesion and permeation into ex vivo human and rat esophageal tissue than non-adhesive nanoparticles (NNPs) and had longer residence times within the rat esophagus in vivo . Incubation with human esophagus (Het-1A) cells confirmed BNPs' biocompatibility at clinically relevant concentrations. In a rat model of achalasia, nifedipine-loaded BNPs significantly enhanced esophageal drug exposure, increased therapeutic efficacy, and reduced systemic drug exposure compared to NNPs and free drug. The safety of BNPs was demonstrated by an absence of intestinal, hepatic, and splenic toxicity following administration. This study is the first to demonstrate the efficacy of BNPs for esophageal drug delivery and highlight their potential for improving the lives of patients suffering with esophageal conditions.

This study reports an ultrasound-mediated and two-dimensional (2D) porous vermiculite nanosheets (VMT NSs)-based nanocatalyst platform (Arg@VMT@PDA-PEG) that synergistically harnessed the Fenton reaction-based chemodynamic therapy (CDT), 2D semiconductor-based sonodynamic therapy (SDT) and nitric oxide (NO)-based gas therapy for combination cancer therapy. The tumor microenvironment responsive degradation of polydopamine (PDA) shell could not only prevent L-Arg, a NO donor, leakage during blood circulation, but also selectively release the active sites of VMT NSs for catalytic reactions in tumor cells. Additionally, the Fenton reactions mediated by the abundant Fe2+/Fe3+ in VMT NSs could efficiently produce ·OH and consume glutathione (GSH) for CDT. Moreover, the reactive oxygen species (ROS, ·OH and ·O 2 −) produced by ultrasound-triggered Arg@VMT@PDA-PEG could not only execute SDT but also oxidize L-Arg to NO for synergetic gas therapy. The results show that the transformation of ROS to NO can enhance curative efficacy owing to the ability of NO with much longer life-time in freely diffusing into cells from intercellular space. This biodegradable Arg@VMT@PDA-PEG nanocatalytic platform integrating three different catalytic reactions provides a new therapeutic paradigm for combination cancer therapy. [Display omitted] [ABSTRACT FROM AUTHOR]