The consequences caused by bacterial resistance are becoming more and more serious. The rate of antibiotic development is far behind the rate of bacterial resistance, so it is urgent to develop a new drug system. In this study, photoresponsive nanogels based on hyaluronic acid were prepared and loaded with ciprofloxacin as a model molecule. The results showed that the nanogels had the advantages of high stability and good cytocompatibility. The inhibition effect of drug-loaded nanogels after light irradiation on the growth of Staphylococcus aureus and Salmonella typhimurium was significantly better than that before light irradiation, and ciprofloxacin could be released on demand and in control. This strategy is of great significance to reduce the unnecessary use of antibiotics and weaken bacterial resistance.

Dry eye disease (DED) is a prevalent ocular disorder characterized by unstable tear film condition with loss of aqueous or mucin, excessive oxidative stress, and inflammation, leading to discomfort and potential damage to the ocular surface. Current DED therapies have shown restricted therapeutic effects such as frequent dosing and temporary relief with potential unwanted side effects, urgently necessitating the development of innovative efficient therapeutic approaches. Herein, we developed rosmarinic acid (RosA) conjugated gelatin nanogels loading diquafosol sodium (DQS), DRGNG, for simultaneous ROS-scavenging and mucin-secreting DED treatment. Mechanically, DRGNG suppressed the ROS production, reduced inflammatory factors, and prompted mucin secretion in vitro and in vivo. The whole transcriptome RNA sequencing in vitro further provided a detailed analysis of the upregulation of anti-oxidant, anti-inflammatory, and mucin-promotion pathways. Therapeutically, both in evaporative DED and aqueous deficient DED models, the dual-functional DRGNG could prolong the retention time at the ocular surface, efficiently suppress the oxidative stress response, reverse ocular surface morphology, and recover tear film homeostasis, thus alleviating the DED when the dosage is halved compared to the commercial Diquas®. Our findings contribute to developing innovative therapies for DED and offer insights into the broader applications of nanogels in ocular drug delivery and oxidative stress-related conditions.

The challenges posed by intractable relapse and metastasis in cancer treatment have led to the development of various forms of photodynamic therapy (PDT). However, traditional drug delivery systems, such as virus vectors, liposomes, and polymers, often suffer from issues like desynchronized drug release, carrier instability, and drug leakage during circulation. To address these problems, we have developed a dual-prodrug nanogel (PVBN) consisting of Pyro (Pyropheophorbide a) and SAHA (Vorinostat) bound to BSA (Bovine Serum Albumin), which facilitates synchronous and spontaneous drug release in situ within the lysosome. Detailed results indicate that PVBN-treated tumor cells exhibit elevated levels of ROS and Acetyl-H3, leading to necrosis, apoptosis, and cell cycle arrest, with PDT playing a dominant role in the synergistic therapeutic effect. Furthermore, the anti-tumor efficacy of PVBN was validated in melanoma-bearing mice, where it significantly inhibited tumor growth and pulmonary metastasis. Overall, our dual-prodrug nanogel, formed by the binding of SAHA and Pyro to BSA and releasing drugs within the lysosome, represents a novel and promising strategy for enhancing the clinical efficacy of photochemotherapy.

Dexamethasone (DEX) has been demonstrated to inhibit the inflammatory corneal neovascularization (CNV). However, the therapeutic efficacy of DEX is limited by the poor bioavailability of conventional eye drops and the increased risk of hormonal glaucoma and cataract associated with prolonged and frequent usage. To address these limitations, we have developed a novel DEX-loaded, reactive oxygen species (ROS)-responsive, controlled-release nanogel, termed DEX@INHANGs. This advanced nanogel system is constructed by the formation of supramolecular host-guest complexes by cyclodextrin (CD) and adamantane (ADA) as a cross-linking force. The introduction of the ROS-responsive material, thioketal (TK), ensures the controlled release of DEX in response to oxidative stress, a characteristic of CNV. Furthermore, the nanogel\'s prolonged retention on the corneal surface for over 8 h is achieved through covalent binding of the integrin β1 fusion protein, which enhances its bioavailability. Cytotoxicity assays demonstrated that DEX@INHANGs was not notably toxic to human corneal epithelial cells (HCECs). Furthermore, DEX@INHANGs has been demonstrated to effectively inhibit angiogenesis in vitro. In a rabbit model with chemically burned eyes, the once-daily topical application of DEX@INHANGs was observed to effectively suppress CNV. These results collectively indicate that the nanomedicine formulation of DEX@INHANGs may offer a promising treatment option for CNV, offering significant advantages such as reduced dosing frequency and enhanced patient compliance.

Nanogels offer hope for precise drug delivery, while addressing drug delivery hurdles is vital for effective prostate cancer (PCa) management. We developed an injectable elastin nanogels (ENG) for efficient drug delivery system to overcome castration-resistant prostate cancer (CRPC) by delivering Decursin, a small molecule inhibitor that blocks Wnt/βcatenin pathways for PCa. The ENG exhibited favourable characteristics such as biocompatibility, flexibility, and low toxicity. In this study, size, shape, surface charge, chemical composition, thermal stability, and other properties of ENG were used to confirm the successful synthesis and incorporation of Decursin (DEC) into elastin nanogels (ENG) for prostate cancer therapy. In vitro studies demonstrated sustained release of DEC from the ENG over 120 h, with a pH-dependent release pattern. DU145 cell line induces moderate cytotoxicity of DEC-ENG indicates that nanomedicine has an impact on cell viability and helps strike a balance between therapeutics efficacy and safety while the EPR effect enables targeted drug delivery to prostate tumor sites compared to free DEC. Morphological analysis further supported the effectiveness of DEC-ENG in inducing cell death. Overall, these findings highlight the promising role of ENG-encapsulated decursin as a targeted drug delivery system for CRPC.

Nanozymes have recently become a research hotspot because of the advantages of good stability, excellent catalytic performance and easy storage in comparison to natural enzymes. Nanozymes with oxidase-like activity get special attention because they needn\'t the participation of hydrogen peroxide. In this paper, poly(N-isopropylacrylamide) nanogel with oxidase-like activity was synthesized for the first time. The catalytic mechanism was explored by EPR and UV spectroscopy after adding specific trapping agents of ROS, and the results showed that PNIPAM NG can catalyze O2 to 1O2. In the presence of PNIPAM NG, o-phenylenediamine (OPD) and ascorbic acid (AA) can be oxidized to 2,3-diaminophenazine (oxOPD) and dehydroascorbic acid (DHA), and DHA can further react with OPD to produce a fluorescence substance. The colorimetric and fluorescence detection platforms for AA were constructed based on the above principles. Both platforms have satisfactory results in real samples. The fluorescence platform has better sensitivity and selectivity than the colorimetric platform.

UNASSIGNED: To improve the bioavailability of trans-resveratrol (trans-Res), it is commonly co-delivered with antioxidant bioactives using a complex synthetic intestinal targeted carrier, however, which makes practical application challenging.
UNASSIGNED: A nanogel (Ngel), as broad-spectrum autonomous ROS scavenger, was prepared using selenized thiolated sodium alginate (TSA-Se) and crosslinked with calcium lactate (CL) for loading trans-Res to obtain Ngel@Res, which maintained spherical morphology in the upper digestive tract but broke down in the lower digestive tract, resulting in trans-Res release.
UNASSIGNED: Under protection of Ngel, trans-Res showed enhanced stability and broad-spectrum ROS scavenging activity. The synergistic mucoadhesion of Ngel prolonged the retention time of trans-Res in the intestine. Ngel and Ngel@Res increased the lifespan of Caenorhabditis elegans to 26.00 ± 2.17 and 26.00 ± 4.27 days by enhancing the activity of antioxidases, upregulating the expression of daf-16, sod-5 and skn-1, while downregulating the expression of daf-2 and age-1.
UNASSIGNED: This readily available, intestinal targeted selenized alginate-based nanogel effectively improves the bioactivity of trans-Res.

Despite numerous advantages of liposomes in treating rheumatoid arthritis (RA), the in vivo stability remains a critical issue. Current strategies for improving liposomal stability often compromise their original properties. Herein, we designed an alginate nanogel-embedded liposome aiming at retaining those inherent advantages while enhancing their in vivo stability. The introduction of alginate network within the liposome core can provide mechanical support and controlled drug release without affecting the surface properties. Results showed the cross-linking of alginate network within the inner core of liposomes elevated the particle rigidity to 3 times, allowing for improved stability and decreased drug leakage. Moreover, this nanogel-embedded liposome with optimized elasticity obviously facilitated cellular uptake in inflammatory macrophages. When entering blood circulation, increased rigidity altered the composition of protein corona on the particle surface, resulting in 2-fold increase in circulation time and improved drug accumulation in arthritic joints. When anti-inflammatory chlorogenic acid (CA) was encapsulated into the nanogel network, this CA-loaded nanogel-embedded liposome significantly inhibited ROS production and inflammatory response, ultimately achieved superior therapeutic outcome in arthritic rats. Results demonstrated that this nanogel-embedded liposomes can essentially retain the inherent advantages and overcome the drawbacks of liposomes, thereby improving the drug delivery efficiency.

Antitumor agents often lack effective penetration and accumulation to achieve high therapeutic efficacy in treating solid tumors. Nanomotor-based nanomaterials offer a potential solution to address this obstacle. Among them, nitric oxide (NO) based nanomotors have garnered attention for their potential applications in nanomedicine. However, there widespread clinical adoption has been hindered by their complex preparation processes. To address this limitation, we have developed a NO-driven nanomotor utilizing a convenient and scalable nanogel preparation procedure. These nanomotors, loaded with the fluorescent probe / sonosensitizer chlorin e6 (Ce6), were specifically engineered for sonodynamic therapy. Through comprehensive in vitro investigations using both 2D and 3D cell models, as well as in vivo analysis of Ce6 fluorescent signal distribution in solid tumor models, we observed that the self-propulsion of these nanomotors significantly enhances cellular uptake and tumor penetration, particularly in solid tumors. This phenomenon enables efficient access to challenging tumor regions and, in some cases, results in complete tumor coverage. Notably, our nanomotors have demonstrated long-term in vivo biosafety. This study presents an effective approach to enhancing drug penetration and improving therapeutic efficacy in tumor treatment, with potential clinical relevance for future applications.

Asthma is a chronic and heterogeneous disease affecting the lungs and respiratory tract. In particular, the neutrophil subtype of asthma was described as persistent, more severe, and corticosteroid-resistant. Growing evidence suggested that nontypeable Haemophilus influenzae (NTHi) infection contributes to the development of neutrophilic asthma, exacerbating clinical symptoms and increasing the associated medical burden. In this work, arginine-grafted chitosan (CS-Arg) was ionically cross-linked with tris(2-carboxyethyl) phosphine (TCEP), and a highly-efficient antimicrobial agent, poly-ε-L-Lysine (ε-PLL), was incorporated to prepare ε-PLL/CS-Arg/TCEP (ECAT) composite nanogels. The results showed that ECAT nanogels exhibited highly effective inhibition against the proliferation of NTHi, Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). In addition, ECAT nanogels could effectively inhibit the formation of mucins aggregates in vitro, suggesting that the nanogel might have the potential to destroy mucin in respiratory disease. Furthermore, in the ovalbumin (OVA)/NTHi-induced Balb/c mice model of neutrophilic asthma, the number of neutrophils in the alveolar lavage fluid and the percentage of inflammatory cells in the blood were effectively reduced by exposure to tower nebulized administration of ECAT nanogels, and reversing airway hyperresponsiveness (AHR) and reducing inflammation in neutrophilic asthma mice. In conclusion, the construction of ECAT nanogels was a feasible anti-infective and anti-inflammatory therapeutic strategy, which demonstrated strong potential in the clinical treatment of neutrophilic asthma.