Ultraviolet radiation induces skin carcinogenesis through DNA damage and oxidative stress, driving demand for high-efficacy sunscreens. Current organic filters (e.g., octyl methoxycinnamate, OMC) suffer from narrow spectral coverage and phototoxicity. To address these limitations, we engineered OMC-loaded hollow mesoporous silica nanoparticles with polydopamine coating (OMC@HMSN@PDA). This nanoplatform achieved: (i) synergistic broad-spectrum protection, the sun protection factor (SPF) and UVA protection factor (UVAPF) up to 54 ± 0.74, 26.8 ± 6 with the concentration of 6 wt% OMC respectively, exceeding OMC@HMSN by 10.4-fold in UVB and 11.2-fold in UVA attenuation; (ii) 93.1 ± 1.2 % of DPPH and 98.5 ± 2.5 % of ABTS radical scavenging at 10 µg mL-1, and 94.6 ± 0.03 % intracellular reactive oxygen species (ROS) suppression; and (iii) prevention of the payload leakage and photo-instability of OMC, resolution of OMC's phototoxicity with above 80 % cell viability in vitro. In vivo studies demonstrated prevention of UV-induced epidermal hyperplasia and lower inflammation. This technology establishes a promising approach for photoprotection integrating UV filtering, antioxidant activity, and enhanced safety.

Infectious tissue damage evolves through a stage-dependent cascade, progressing from initial pathogen invasion and immune dysfunction to subsequent failure in tissue regeneration. While nanotechnology offers promising strategies for infection control, its inability to dynamically adapt to the changing pathological environment remains a limitation. Here, a programmable single-particle core-shell nanoplatform (Z-Lyc@ELP) was constructed by integrating hierarchical structural separation with environment-responsive mechanisms, enabling sequential intervention aligned with infection progression. The outer shell, composed of unsaturated phospholipid-doped garlic-derived exosome-like nanovesicles (GELNs), exhibits reactive oxygen species (ROS) responsiveness. At the early stage of infection, it rapidly releases polymyxin B (PMB) and immunoregulatory molecules to remodel the pathogenic microenvironment. As lesion acidification deepens, the ZIF-8 core gradually decomposes, releasing lycopene (Lyc) and Zn2+ ions. This second-wave intervention effectively scavenges excessive ROS, promotes macrophage M2 polarization, and upregulates angiogenic factors, thereby reactivating intrinsic tissue repair. In vivo, the Z-Lyc@ELP nanoplatform achieved a 98.1% healing rate of infectious burn wounds after 16 days and an 80% survival rate in sepsis mice over 10 days. This pathology-guided strategy, combining environment-responsive mechanisms with sequential therapeutic release, offers a dynamic nanoplatform for precise infection treatment and tissue repair.

Wound healing is a long-term, multi-stage biological process that relies on the use of biomedical materials to realize comprehensive wound management, encompassing hemostasis, wound healing and promoting anti-scar. In this review, the applications of various hemostatic and bioactive materials in full-course wound management are underscored by summarizing their progress, current status and developing trend in wound healing. Adhesive hydrogels and degradable hemostatic emboli with biomimetic designs have been developed to achieve rapid hemostasis and hence enhance repair efficiency through accelerating clot formation. Smart drug delivery dressings and tissue engineering scaffolds can promote cell proliferation, angiogenesis and matrix remodeling to accelerate wound healing by providing infection monitoring and programmable drug release. Biomaterials are able to effectively prevent abnormal scar formation by controlling mechanical factors, sustaining drug release and regulating fibroblast transformation. These hemostatic and bioactive materials integrate multiple functions, overcoming the limitations of traditional dressings, leading to remarkably improving wound healing speed and quality. Nevertheless, material safety, accessibility and multifunctional optimization remain the major challenges that should be addressed urgently. Smart responsive biomaterials, personalized regenerative bio-scaffolds and full-course management strategies are expected to offer advanced therapeutic options for wound healing, holding great potential for clinical applications.

Infected deep burn wounds represent a severe clinical challenge due to microbial invasion, persistent inflammation, impaired tissue regeneration, and subsequent scar formation. To address these issues, we developed stimuli-responsive and on-demand removable hydrogel dressing (AMP@GPQCD) with injectability, antibacterial, antioxidant, anti-inflammatory, and pro-angiogensis capacities for comprehensive management of deep burn wounds. The AMP@GPQCD hydrogel was composed of phenylboronic acid-modified gelatin methacrylate (GelMA-PBA), catechol-decorated chitosan (CS-DA), vinyl-terminated VEGF-mimetic peptide (QKMA), and an ultrashort antimicrobial lipopeptide (AMP, C12-RFKFRF-NH2). The dual crosslinking GPQCD hydrogel was fabricated through the dynamic phenylborate bonds between GelMA-PBA and CS-DA, and UV-initiated polymerization of GelMA and QKMA. The acidic and oxidative microenvironment at the infected burn wounds triggered the dissociation of phenylborate bonds, leading to the rapid release of the encapsulated AMP. Notably, the on-demand and painless removal of the hydrogel dressing could be achieved by applying glucose solution through competition with the catechol groups on CS-DA for binding to phenylboronic acid. In vivo studies demonstrated advanced burn wound healing via hemostasis, antibacterial, antioxidant, anti-inflammation, angiogenesis, and tissue regeneration, promoting the formation of a healthier basket-weave collagen network, thereby reducing the tendency towards fibrosis. This study provides a transformative therapeutic solution for infected deep burn wounds. Statement of significance A dual-crosslinked smart hydrogel (AMP@GPQCD) with multi-stimuli responsiveness was constructed. The dynamic borate network of AMP@GPQCD hydrogels in response to acidic pH and high ROS level could rapidly release ultrashort antimicrobial lipopeptides and scavenge excess ROS, followed by effective macrophages polarization into M2 phenotype for comprehensive anti-infection and inflammation regulation. AMP@GPQCD hydrogels can continuously promote fibroblast proliferation/migration and angiogenesis through covalently grafted VEGF mimetic peptides, capable of enhancing collagen remodeling for reducing fibrosis tendency. In addition, the glucose-responsive AMP@GPQCD hydrogel can be painlessly removed on demand, avoiding secondary damage to the wound.

Over 15% of acne patients manifest moderate to severe clinical presentations, accompanied with bacterial infection, long-term inflammatory responses, dysregulated lipid metabolism, and post-acne skin atrophy. Although microneedles (MNs) represent an effective transdermal drug delivery system for acne treatment, the therapeutic effects on the restoration of dysregulated lipid metabolism and the prevention of atrophic acne scars are still lacking. Herein, we develop proteoglycan-mimetic comb polymer (HMC)-based dissolving microneedles (HMC-PEP MNs) with encapsulation of therapeutic peptides. This system effectively targets the acne pathophysiological pathways involving bacterial colonization, lipid dysregulation, chronic inflammation and impaired tissue repair. Specifically, HMC enables sustained release of antimicrobial and anti-inflammatory peptides via multiple non-covalent interactions. HMC-PEP MNs display significant efficacy via eradicating Cutibacterium acnes infection, suppressing pro-inflammatory mediator expression, and reducing the TREM2/M2 macrophage ratio. Integrated transcriptomic and metabolomic analysis reveals that HMC-PEP MNs effectively regulate cholesterol and linoleic acid metabolism, inhibit pro-inflammatory signaling transduction, and reduce keratinocyte proliferation and differentiation by inhibiting the IGF1/IGF1R/PI3K/AKT/mTOR signaling pathway. Interestingly, HMC-PEP MNs also promote collagen synthesis and ameliorate fibroblast dysfunction, thereby preventing the formation of post-acne dermal atrophy. This study presents an effective therapeutic strategy for acne and elucidates the underlying mechanisms of HMC-PEP MNs, demonstrating considerable promise for clinical translation.

An orthogonal strategy is employed to synthesize the antibacterial adjuvant GCPP5 through functionalization of pillar[5]arene with guanidinocarbonyl pyrrole (GCP) units. This design enables the construction of a supramolecular nanoassembly (GCPP5⊃CFZ⊃EsY-CN) for multimodal treatment of Staphylococcus aureus (S. aureus) infections. The system integrates a membrane-targeting GCP group, the antibiotic cefazolin (CFZ), and a photosensitizer eosin Y derivative (EsY-CN) via host-guest interactions, including the binding of CFZ to the nitrogen sites on the GCP moieties and the encapsulation of EsY-CN within the electron-rich cavity of the pillar[5]arene. These programmed interactions realize a multimodal "targeting-chemical inhibition-photodynamic oxidation" antibacterial strategy. Experimental results show that the photoactivated assembly effectively generates reactive oxygen species, eradicates S. aureus at extremely low concentrations (5 to 10 nm), inhibits and eliminates biofilms, and mitigates the increase in the minimum inhibitory concentration during serial-passage assays under the tested conditions. In vivo wound models confirm that the nanoassembly could accelerate the healing process and reduce bacterial load while exhibiting good biocompatibility. By exploiting an orthogonal supramolecular design, this work establishes a promising multimodal antimicrobial strategy for combating light-accessible biofilm-associated infections.

Bacterial biofilms in infected wounds and implant-associated infections are highly tolerant to antibiotics and often coexist with excessive inflammatory reactive oxygen species (ROS), resulting in treatment failure and delayed healing. Here, we report a photothermal-responsive curcumin-loaded gold nanorod-silica hybrid nanocomposite (Cur@T-Au) for antibiotic-free infection control and infectious microenvironment remodeling. Gold nanorods were electrostatically assembled onto hollow mesoporous silica nanoparticles (HAu) and further coated with polyethyleneimine to yield a positively charged carrier (T-Au) with bacterial-adhesive capability. Upon near-infrared irradiation, Cur@T-Au demonstrated rapid photothermal hyperthermia synergized with photothermal-responsive triggered structural degradation for controlled release of curcumin, exhibiting broad-spectrum antibacterial activity and potent antibiofilm efficacy. Meanwhile, Cur@T-Au effectively scavenged free radicals and reduced intracellular ROS, and markedly modulated inflammatory responses. In vivo, Cur@T-Au significantly reduced bacterial burden and accelerated healing in infected wound and implant-related infection models, accompanied by improved tissue regeneration and inflammation resolution. Collectively, Cur@T-Au provides an on-demand photothermal-responsive sequential therapeutic strategy that integrates bactericidal action, ROS mitigation and degradability, offering a promising non-antibiotic platform for treating biofilm-associated infections.

As the rapid growth of aging population, intervertebral disc degeneration (IVDD) becomes a prevalent degenerative disorder in clinical practice. Ferroptosis-induced senescence in nucleus pulposus cells (NPCs) represents a primary pathological mechanism underlying IVDD. Strategies for reducing ferroptosis to delay NPC senescence hold prospects for therapeutic advances. According to previously reported proteomic profiles of apoptotic extracellular vesicles (ApoEVs), we noticed that most key ferroptosis-regulating proteins were identified in the ApoEVs proteome, including upregulation of Glutathione Peroxidase 4 (GPX4). In this study, we developed injectable hydrogel microspheres (HMs) integrating with senescent NPC-targeting ApoEVs as GPX4 delivery vehicle and anti-inflammatory diclofenac sodium (DFS) for IVDD treatment. The effect of ApoEVs on reducing NPC ferroptosis and reversing NPC senescence-related metabolic dysfunction and damage was reinforced through modification of reactive oxygen species (ROS) responsive and senescent NPC-targeting peptide. In vivo experiments and single cell RNA sequencing analysis elucidated that the senescence-targeted system significantly attenuated ferroptosis and inflammatory pathways, and prevented the transformation of inflammatory NPC phenotypes, thereby offering opportunities for reducing senescent NPCs from ferroptosis and mitigating IVDD progression.

The development of heart valve prostheses with regenerative capabilities offers significant potential to overcome the limitations of existing commercial artificial valves in clinical practice. Immune modulation plays a crucial role in heart valve regeneration by reversing the coagulation and inflammatory microenvironment, thereby facilitating recellularization. In this study, a biosynthesis factory is constructed on decellularized heart valves (DHVs) to continuously convert the abundant heme in the blood into immunomodulators, supporting long-term immune modulation and tissue regeneration. This biosynthesis factory is achieved through a grafting from DNA hydrogel, utilizing tailored rolling circle amplification (RCA) on DHVs. Anti-coagulation NU172 aptamers are incorporated into the DNA hydrogel to recruit heme from the bloodstream, while heme oxygenase 1 (HO-1) is encapsulated to simultaneously convert heme into biliverdin. This system ensures the sustained production of biliverdin, facilitating anti-inflammatory immune modulation and reactive oxygen species (ROS) scavenging, thus creating a regenerative immune microenvironment. Additionally, the DNA coating is further crosslinked with zwitterionic polymers, which protect the functional DNA layer and provide anti-calcification and anti-adhesion properties. This comprehensive design promotes full endothelial cell coverage and significant extracellular matrix remodeling within one-month post-implantation.

Local inflammation modulation and stem cell therapy have attracted much attention in the treatment of intervertebral disc degeneration (IDD). However, severe oxidative stress and limited nucleus pulposus (NP)-like differentiation of stem cells largely impair biomaterial implantation's therapeutic efficacy. Due to their excellent performance in injectability and flowability, and minor compression to NP tissue, hydrogel microspheres have become an attractive carrier for IDD treatment. Herein, an injectable hydrogel microsphere consisting of Wnt5a-mimetic peptide Foxy5- and the antioxidative peptide-grafted gelatin methacryloyl matrix (GFA), was developed as a stem cell delivery system for IDD therapy. Being fabricated and encapsulating bone marrow-derived mesenchymal stem cells (BMSCs) using the microfluidic technology, GFA hydrogel microspheres ameliorate IDD by promoting inflammation inhibition, NP-like differentiation and extracellular matrix regeneration. They efficiently eliminated reactive oxygen species, and downregulated the inflammation level through the inhibition of interleukin-17B/nuclear factor-κB signaling pathway. Moreover, the NP-like differentiation of BMSCs was effectively stimulated by Foxy5 via the calcium/calmodulin dependent protein kinase kinase 2/protein kinase A/sex determining region Y box protein 9 signaling pathway, thereby leading to a rebalance between the generation and degradation of NP matrix. In vivo rat IDD model demonstrated that BMSC-loaded GFA hydrogel microspheres mitigated local inflammation, preserved disc height, and promoted intervertebral disc regeneration. In conclusion, this study introduces an BMSC-loaded injectable hydrogel microspheres as a promising therapy for regulating the microenvironment and alleviating the progression of IDD.

Breast cancer is one of the most prevalent malignant tumors worldwide and a leading cause of cancer-related mortality, underscoring the urgent need for innovative therapeutic strategies. In this study, we developed an injectable hydrogel-based system, in which polyvinylpyrrolidone (PVP)-modified NiS2-x@PVP nanospheres were incorporated with metformin hydrochloride (MH) and dispersed in a hyaluronic acid (HA) hydrogel matrix to form the NiS2-x@PVP@HA tumor treatment platform. This system exhibits excellent photothermal performance under near-infrared (NIR) light irradiation and can be employed for tumor photothermal therapy (PTT). The Ni2+ released from the degradation of NiS2-x@PVP nanospheres can catalyze the decomposition of endogenous hydrogen peroxide in tumor cells, thereby generating toxic hydroxyl radicals for chemodynamic therapy (CDT). By altering the HA concentration, the internal pore structure, mechanical properties, drug release behavior, and swelling capacity of the hydrogel can be modulated. The loaded antitumor drug MH further enhances the therapeutic efficacy. Under NIR and ultrasound stimulation, this platform enables controlled drug release. In vitro and in vivo experiments have demonstrated that the NiS2-x@PVP@HA hydrogel achieves the synergistic treatment of PTT/CDT/chemotherapy for tumor tissues. Kyoto Encyclopedia of Genes and Genomes pathway analysis suggested that activation of the MAPK signaling pathway was a key mechanism underlying tumor cell death. This work presents a rational design strategy that addresses the related challenges in breast cancer and promotes precise cancer therapy.

Peptides possess great potential in drug development due to their high selectivity and excellent biocompatibility, while their poor in vivo stability and short half-life limit the practical applications. Peptide-polymer conjugates, by linking peptides with synthetic or natural polymeric materials, significantly improve their pharmacokinetic properties and therapeutic efficacy. This review systematically summarizes the design principle and synthetic strategies of conjugates, including covalent bonding, physical association, and self-assembly mechanisms, and elaborates on their applications in drug delivery, immunotherapy, and tissue engineering. The review also discusses current challenges, such as difficulties in controlling conjugation sites and increased immunogenicity, and envisions the development of responsive intelligent systems to provide a theoretical basis and reference for future clinical translation of peptide-based therapeutics.

The multiple hydrogen-bond has been introduced as a reversible driving force for directing the assembly of polymer-grafted nanoparticles (PGNPs). The complementary hydrogen-bonds among the polymer ligands lead to the spontaneous aggregation of PGNPs. However, it may also induce the uncontrollable aggregation of PGNPs into assemblies with non-uniform size, even irregular precipitates, due to the immoderate agglomeration associated with the strong interactions of multiple hydrogen-bonds. This severely limits the stable dispersion of PGNP aggregates in a solvent and their applications. In this work, the gold nanoparticles (AuNPs) grafted with thymine-terminated polystyrene (AuNP@PS-Thy) and diaminopyridine-terminated polystyrene (AuNP@PS-Dap) were synthesized, respectively. Their thermal-responsive assembly behavior in an organic solvent was systematically studied. By optimizing the assembly conditions, i.e., the concentration of PGNPs and the incubation time, the assemblies of AuNP@PS-Thy/AuNP@PS-Dap with controllable size were obtained. Interestingly, the assemblies deposited on a solid substrate showed excellent photothermal antimicrobial activities under irradiation of 808 nm and 655 nm lasers. The killing percentage of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) could reach 99% after irradiating for 10 min. This work establishes an approach for controlling the hydrogen-bonding-induced assembly behavior of PGNPs, which may be extended to construct functional metamaterials with controllable structures.

Drug-resistant biofilm infection is an extremely serious clinical problem, that easily leads to failure of antibiotic treatment. Although gold nanoparticles (AuNPs) as photothermal agents have been widely used in biofilm eradication, there are still challenges to be addressed, such as insignificantly redshifted absorption and slow assembly process of aggregated AuNPs. Herein, we developed an acidity-activated dispersion-to-aggregation transition to enhance the accumulation of self-complementary zwitterionic peptide-decorated AuNPs for photothermal eradication of drug-resistant biofilm infections. AuNPs were decorated with self-complementary zwitterionic peptides (ZP1 and ZP2) coupled with pH-sensitive anhydride (DMA) and pH-insensitive anhydride (SA), respectively. ZP2-decorated AuNPs with DMA modification (AuNP@ZP2(DMA)) exhibited prolonged blood circulation and enhanced accumulation in acidic biofilm microenvironment. Moreover, the electrostatic attraction between self-complementary ligands drove AuNPs to form closely packed aggregates with strong near-infrared absorption, leading to in vivo photoacoustic imaging ability and photothermal effect against drug-resistant bacteria and fungus, as well as microbial biofilms. AuNP@ZP2(DMA) with longer charge domains and a polyethylene glycol oligomer spacer showed greater photothermal antimicrobial and biofilm resistance in vitro and in vivo. This study develops an innovative acidity-activated AuNP photothermal agent, which provides an effective approach for treatment of biofilm infections.

BACKGROUND:There are various methods to assess interaction effects. However, current methods have limitations, and quantification of interaction effects is rarely performed. This study aimed to develop a unified quantitative framework for assessing interaction effects. METHODS:We proposed a novel framework using log-linear models with a product term(s) across the exposures that generates parametric bi-variate association and interaction effect surfaces and allows flexible functional forms for exposures in the interaction term(s). In a case study, we assessed the interaction effects between temperature and air pollution (i.e., PM2.5, NO2, and O3) on risk for kidney-related conditions in New York State (2007-2016) using a case-crossover design with conditional logistic models. Our measures of exposure were the moving averages at lag 0-5 days for air pollution (linear) and daytime mean outdoor wet-bulb globe temperature (WBGT; using a natural cubic spline). RESULTS:We derived closed-form expressions for the magnitude of multiplicative interaction effects (the joint relative risk divided by the product of the two conditional relative risks) and their uncertainties. In the case study, we found a Bonferroni-corrected significant multiplicative interaction effect (IE) between outdoor WBGT at the 99th percentile (median as the reference) and (1) PM2.5 (per 5 μg/m3 increase, IE = 1.052; 95 % confidence interval [CI]: 1.019, 1.087) for acute kidney failure and (2) O3 (per 5 ppb increase; IE = 1.022; 95 % CI: 1.008, 1.036) for urolithiasis (the latter being inconclusive based on the sensitivity analysis). CONCLUSIONS:Our framework allows different functional forms of exposure variables in the interaction term, quantifies the magnitudes of entire-exposure-range (in addition to discrete exposure level) multiplicative interaction effects and their uncertainties in a categorical or continuous (linear or non-linear) manner, and harmonizes the two-way evaluation of effect modification. The case study underscores co-consideration of heat and air pollution when estimating health burden and designing heat/pollution alert systems.

Injectable hydrogel has attracted appealing attention for skin wound treatment. Although multifunctional injectable hydrogels can be prepared by introducing bioactive ingredients with antibacterial and antiinflammatory capabilities, their preparation remains complicated. Herein, a polyphenol-based supramolecular injectable hydrogel (PBSIH) based on polyphenol gallic acid and biological macromolecule sodium alginate is developed as a wound dressing to accelerate wound healing. We show that such PBSIH can be rapidly formed within 15 s by mixing the sodium alginate and gallic acid solutions based on the hydrogen bonding and hydrophobic interactions. The PBSIH shows excellent cytocompatibility, antibacterial, and antioxidant properties, which enhance infected wound healing by inhibiting bacterial infection and alleviating inflammation after treatment of 11 days. Moreover, we show that the preparative strategies of injectable supramolecular hydrogels can be extended to other polyphenols, including protocatechuic and tannic acids. This study provides a facile yet highly effective method to design injectable polyphenol- sodium alginate hydrogel for wound dressing based on naturally bioactive ingredients.

Combined photodynamic and photothermal therapy (PDT and PTT) can achieve more superior therapeutic effects than the sole mode by maximizing the photon utilization, but there remains a significant challenge in the development of related single-molecule photosensitizers (PSs), particularly those with type I photosensitization. In this study, self-assembly of squaraine dyes (SQs) is shown to be a promising strategy for designing PSs for combined type I PDT and PTT, and a supramolecular PS (TPE-SQ7) has been successfully developed through subtle molecular design of an indolenine SQ, which can self-assemble into highly ordered H-aggregates in aqueous solution as well as nanoparticles (NPs). In contrast to the typical quenching effect of H-aggregates on reactive oxygen species (ROS) generation, our results encouragingly manifest that H-aggregates can enhance type I ROS (•OH) generation by facilitating the intersystem crossing process while maintaining a high PTT performance. Consequently, TPE-SQ7 NPs with ordered H-aggregates not only exhibit superior combined therapeutic efficacy than the well-known PS (Ce6) under both normoxic and hypoxic conditions but also have excellent biosafety, making them have important application prospects in tumor phototherapy and antibacterial fields. This study not only proves that the supramolecular self-assembly of SQs is an effective strategy toward high-performance PSs for combined type I PDT and PTT but also provides a different understanding of the effect of H-aggregates on the PDT performance.

Hypertrophic scar (HS) considerably affects the appearance and causes tissue dysfunction in patients. The low bioavailability of 5-fluorouracil poses a challenge for HS treatment. Here we show a separating microneedle (MN) consisting of photo-crosslinked GelMA and 5-FuA-Pep-MA prodrug in response to high reactive oxygen species (ROS) levels and overexpression of matrix metalloproteinases (MMPs) in the HS pathological microenvironment. In vivo experiments in female mice demonstrate that the retention of MN tips in the tissue provides a slowly sustained drug release manner. Importantly, drug-loaded MNs could remodel the pathological microenvironment of female rabbit ear HS tissues by ROS scavenging and MMPs consumption. Bulk and single cell RNA sequencing analyses confirm that drug-loaded MNs could reverse skin fibrosis through down-regulation of BCL-2-associated death promoter (BAD), insulin-like growth factor 1 receptor (IGF1R) pathways, simultaneously regulate inflammatory response and keratinocyte differentiation via up-regulation of toll-like receptors (TOLL), interleukin-1 receptor (IL1R) and keratinocyte pathways, and promote the interactions between fibroblasts and keratinocytes via ligand-receptor pair of proteoglycans 2 (HSPG2)-dystroglycan 1(DAG1). This study reveals the potential therapeutic mechanism of drug-loaded MNs in HS treatment and presents a broad prospect for clinical application.

Intralesional injection of 5-fluorouracil for the clinical treatment of hypertrophic scars (HS) remains challenging due to its short half-life, as well as the absence of evidence-based dosage and frequency injection guidelines. Herein, we developed a matrix metalloproteinases (MMPs)/reactive oxygen species (ROS)-responsive injectable prodrug hydrogel (GFP) that exhibits sustained drug release and fluorescence imaging capability, aiming to facilitate the optimization of injection dosage and frequency in HS treatment. The GFP hydrogel comprises gelatin methacryloyl and pendant methacryloyl-decorated tetrapeptide (PPPK) with 5-fluorouracil acetic acid/rhodamine B at the N-terminus. After intralesional injection and blue light irradiation, the crosslinked hydrogel in HS lesions exhibited long-term sustained drug release by consuming overexpressed MMPs and ROS, which could be visualized by fluorescence imaging to guide injection frequency for HS treatment. In addition, due to its exceptional swelling and mechanical properties, the GFP hydrogel exerts a certain pressure inside the HS tissues, functioning as an adjunctive therapy to inhibit HS. Our results demonstrate that the GFP hydrogel can promote fibroblast apoptosis, inhibit collagen synthesis, and remodel the microenvironment of HS. This study presents a promising visualized drug delivery platform that potentially guides the optimization of injection frequency and dosage in the treatment of HS.

In situ polymerization on cell membranes can decrease cell mobility, which may inhibit tumor growth and invasion. However, the initiation of radical polymerization traditionally requires exogenous catalysts or free radical initiators, which might cause side effects in normal tissues. Herein, we synthesized a Y-type diacetylene-containing lipidated peptide amphiphile (TCDA-KFFFFK(GRGDS)-YIGSR, Y-DLPA) targeting integrins and laminin receptors on murine mammary carcinoma 4T1 cells, which underwent nanoparticle-to-nanofiber morphological transformation and in situ polymerization on cell membranes. Specifically, the polymerized Y-DLPA induced 4T1 cell apoptosis and disturbed the substance exchange and metabolism. In vitro assays demonstrated that the polymerized Y-DLPA nanofibers decreased the migration capacity of 4T1 cells, potentially suppressing tumor invasion and metastasis. When administered locally to 4T1 tumor-bearing mice, the Y-DLPA nanoparticles formed a biomimetic extracellular matrix that effectively suppressed tumor growth. This study provides an in situ polymerization strategy that can serve as an effective drug-free biomaterial with low side effects for antitumor therapy.