Fengyi Du

Conjugated polymer‐based phototheranostics have attracted considerable attention for cancer treatment owing to their excellent photothermal properties and biocompatibility. However, integrating efficient photodynamic activity into conjugated polymer systems without compromising their intrinsic photothermal performance remains a major challenge. Here, we report structurally engineered selenophene‐doped polypyrrole nanoplatforms (Ppy‐PSe NPs) for imaging‐guided synergistic phototherapy. Incorporation of selenium‐containing heterocycles into the conjugated polypyrrole framework introduces a pronounced heavy‐atom effect, which promotes intersystem crossing and substantially enhances reactive oxygen species (ROS) generation while preserving broadband near‐infrared (NIR) absorption and efficient photothermal conversion. Upon NIR laser irradiation, Ppy‐PSe induces severe oxidative stress, lysosomal disruption, cytoskeletal collapse, and apoptotic cell death. Mechanistically, ROS‐mediated suppression of HSP90 disrupts the oncogenic JAK2/STAT3 signaling axis, thereby reprogramming tumor thermotolerance and sensitizing malignant cells to photothermal injury. In vivo, Ppy‐PSe exhibits favorable biosafety, efficient tumor accumulation, and robust photoacoustic imaging capability for real‐time therapeutic guidance. Notably, NIR‐triggered treatment achieves complete tumor eradication in a lymphoma xenograft model, particularly under NIR‐II irradiation. This work establishes a multifunctional conjugated polymer nanoplatform that integrates ROS amplification, thermo‐sensitization reprogramming, and imaging‐guided synergistic phototherapy for precision cancer treatment.

Purpose: Monotherapy with photothermal therapy (PTT) hardly achieves durable and significant antitumor efficacy. To further improve the therapeutic effect against tumors, in this study, the chemotherapeutic agent thioridazine (THZ) was loaded into a gel network formed by the Schiff base cross-linking of amino-functionalized graphene quantum dots (NH₂-GQDs) and oxidized dextran. A pH-responsive injectable carbon dot composite hydrogel delivery system (NTD@Gel) with dual effects of photothermal therapy and chemotherapy was thereby constructed. Methods: The techniques including HRTEM, XPS, FTIR, SEM and rheological tests were employed to verify the successful fabrication of NTD@Gel and characterize its physicochemical properties. In vitro and in vivo experiments were conducted to comprehensively evaluate the antitumor efficacy and biosafety of this hydrogel. Results: NTD@Gel exhibited excellent photothermal conversion performance and biocompatibility, and enabled the rapid and sustained release of THZ in the acidic microenvironment. In vitro experiments confirmed that NTD@Gel could synergistically kill Hep1-6 hepatocellular carcinoma cells through photothermal ablation and THZ-induced oxidative damage, and inhibited the oncogenic Akt/Stat3 signaling pathway activation. In vivo experiments demonstrated that NTD@Gel combined with near-infrared laser irradiation significantly inhibited tumor growth, reduced CD133 and CD326 expression on tumor cells, effectively prolonged the survival time of tumor-bearing mice, and caused no obvious pathological damage in the major organs of mice. Conclusion: NTD@Gel can significantly enhance the therapeutic efficacy against hepatocellular carcinoma and reduce the risk of metastasis and recurrence through the synergistic effect of photothermal therapy and chemotherapy.

Conventional chemotherapy is often limited by the physical tumor microenvironment, where an elevated interstitial pressure and dense extracellular matrix collectively impair drug penetration, reduce targeting efficiency, and lead to systemic toxicity. To address these challenges, we proposed an in situ synergistic therapeutic strategy combining nattokinase (NKase) pretreatment with a bioorthogonal chemistry-inspired hydrogel (CuPP@PH). Intratumorally injected NKase effectively reduced tumor stiffness and markedly increased local blood perfusion. Subsequently, the CuPP@PH was rapidly formed in situ via dynamic boronate ester cross-linking between the Copper-functionalized Prussian blue nanozymes (CuPP NZs) and phenylboronic-grafted hyaluronic acid (PH). The embedded CuPP NZs demonstrated significant multienzyme mimetic activity, substantially enhancing photothermal ablation efficacy. Specifically, the CuPP@PH further eradicated residual tumor cells by facilitating the in situ synthesis of cytotoxic copper diethyl dithiocarbamate (CuET) complex from prolonged-retention CuPP NZs and orally administered disulfiram. This work establishes a bioorthogonal-inspired combinatorial strategy that augments in situ chemotherapy and photothermal therapy through remodeling the tumor physical microenvironment.

Surface-engineered probiotics represent a promising therapeutic strategy for treating ulcerative colitis (UC). However, their therapeutic efficacy is often compromised by the complex pathological conditions and limited drug integration capacity. To overcome these therapeutic challenges, we developed a single-cell probiotic encapsulation system featuring with a sandwich-structured nanocoating (LGG@PLD-AS/ALG). The inner poly(L-dopa) (PLD) layer not only exhibited potent radical-scavenging capability, but also facilitated the dynamic loading of anti-inflammatory small molecule drugs (5-aminosalicylic acid, 5-ASA). Specifically, pathological reactive oxygen species (ROS) at the UC site triggered the cleavage of covalent bonds, resulting in on-demand 5-ASA release. Meanwhile, the outer alginate layer enabled intestinal-targeted delivery of probiotics and preventing premature 5-ASA leakage by undergoing pH-responsive degradation. In a dextran sulfate sodium (DSS)-induced murine colitis model, LGG@PLD-AS/ALG effectively promoted restoration of the intestinal barrier, rebalanced gut microbiota and alleviated colonic inflammation. This work proposes a novel single-cell probiotic encapsulation system with a sandwich-structured nanocoating, paving a new avenue for UC therapy.

Photothermal therapy (PTT) faces critical limitations due to tumor hypoxia, intrinsic resistance, and metastasis. To address these challenges, we developed a trimodal nanoplatform (R-R/PB@PPy NEs) by synergizing Prussian blue (PB)/polypyrrole (PPy) nanozymes, tumor suppressor reactivation, and immune modulation. Through Fe³⁺ -mediated one-step oxidative polymerization, PB and PPy were integrated into a hybrid nanozyme and further functionalized with rosiglitazone (PPAR-γ agonist) and rutin (tumor-targeting ligand). The R-R/PB@PPy NEs achieved a photothermal conversion efficiency of 31.6% and catalase/superoxide dismutase-like enzymatic activity, persistently alleviating hypoxia via oxygen generation. Simultaneously, AKT/mTOR-mediated PTEN upregulation suppressed tumor proliferation and metastasis. Rutin-mediated tumor targeting enhanced drug accumulation at tumor sites, which synergistically amplified immunogenic cell death induction, promoting dendritic cell maturation and cytotoxic T-cell infiltration. In vivo, this platform completely inhibited 4T1 tumor growth, eradicated lung metastasis, and prevented recurrence (0% at 56 days) with an 80% long-term survival rate and no systemic toxicity. By unifying catalytic nanozyme design, PTEN-driven sensitization, and immune activation, this study establishes an interdisciplinary strategy to overcome resistance in PTT, offering a translatable approach for precision cancer therapy through tumor microenvironment modulation.

Osteoporosis (OP) represents a significant global health burden, characterized by reduced bone density and an increased risk of fractures due to imbalances in bone remodeling processes. Traditional therapeutic strategies, while mitigating symptoms, often lack the precision to address the multifactorial nature of OP effectively. In recent years, functionalized nanoparticles have emerged as a versatile platform, offering enhanced drug delivery, targeted therapy, and the potential for theranostic applications in OP treatment. This review examines the various types and architectures of functionalized nanoparticles, emphasizing their unique capabilities in targeting bone tissue and modulating bone metabolism. By focusing on their roles in inflammation modulation, oxidative stress reduction, and promoting bone regeneration, we discuss the mechanisms by which these nanoparticles offer multifunctional, synergistic effects. Additionally, we address the challenges in achieving controlled drug release, biocompatibility, and effective bone tissue penetration, proposing future directions that integrate emerging nanotechnologies, biomechanics, and regenerative medicine approaches to optimize therapeutic outcomes. This comprehensive review provides a foundation for the future development of functionalized nanoparticle therapies, positioning them as promising tools for advanced, personalized OP treatment.

Photothermal therapy-triggered whole-tumor cell antigens release has revolutionized in situ cancer vaccine, but insufficient anticancer immunity cycle activation greatly limits its curative effect. Herein, we designed an NIR-triggered cascading in situ vaccine (FCDs-A/C@HGs) by incorporating the Fe-doped carbon dots (FCDs), azo-initiator (AIPH), and immune adjuvant (cyclophosphamide) into the thermosensitive hydrogel. Due to iron doping, the as-prepared FCDs exhibited high photothermal conversion performance and favorable MR imaging capability. Upon intratumoral injection, local hyperthermia mediated by FCDs-A/C@HGs and the subsequent generation of alkyl radicals from AIPH synergistically induced immunogenic cell death in tumor cells. Remarkably, the FCDs-A/C@HGs elicited strong anticancer immune activation by inhibiting regulatory T cells and promoting dendritic cell maturation, thereby enhancing differentiation of cytotoxic CD8+ T cells and memory T cells. This study presents an effective therapeutic platform for in situ tumor suppression and sustained activation of the anticancer immunity cycle.

Purpose: Harnessing helminth-induced immunomodulation offers a novel therapeutic avenue for autoimmune and inflammatory diseases; however, research on helminths against psoriasis remains limited. This study evaluates the effects of the peptide SJMHE1 from Schistosoma japonicum (S. japonicum) on the inflammatory response in imiquimod (IMQ)-induced psoriasis mice and LPS-stimulated keratinocytes, as well as the efficacy of SJMHE1-loaded hydrogel on psoriasis in mice. Methods: SJMHE1 was administered to mice with IMQ-induced psoriasis via topical administration or subcutaneous injection, and effects were evaluated by detecting the skin inflammation of mice. LPS-stimulated HaCaT cells were used to assess the regulatory effects of SJMHE1 in vitro. Additionally, the effects of Poloxamer 407 (P407)-loaded SJMHE1 were evaluated in mice with IMQ-induced psoriasis through topical application. Results: Topical administration and subcutaneous injection of SJMHE1 alleviated psoriasis-like skin lesions, improved PASI scores, reduced epidermal thickness and dermal inflammatory cell infiltration, and decreased expression of Ki67, a marker of keratinocyte proliferation or differentiation. SJMHE1 modulated pro-inflammatory and anti-inflammatory cytokine expression in LPS-treated HaCaT cells, down-regulating NF-κB and STAT3 activation. Both SJMHE1-loaded hydrogel and SJMHE1 treatment alleviated IMQ-induced psoriasis-like skin lesions, improved PASI scores, reduced the number of Ki67-positive epidermal cells, decreased the spleen index and T-cell infiltration, increased the proportion of regulatory T cells (Tregs), and decreased the percentage of Th17 cells, alongside reducing inflammatory cytokine expression and NF-κB and STAT3 activation in skin lesions. Notably, weight changes in the SJMHE1-loaded gel group were less than those in the betamethasone-positive control group on days 6, 7, and 8 post-IMQ administration. Conclusion: SJMHE1-loaded hydrogel and SJMHE1 treatment inhibited NF-κB and STAT3 activation in skin lesions, improved Th17/Treg balance, and reduced inflammatory cytokine expression in psoriasis mice, thereby ameliorating psoriatic lesion symptoms. Furthermore, SJMHE1-loaded hydrogel exhibited fewer side effects compared to betamethasone, positioning it as a promising strategy against psoriasis.