Biomaterials最新文献

Photodynamic therapy (PDT) offers spatiotemporally controlled tumor ablation via photosensitizer-mediated singlet oxygen (¹O₂) generation, yet its application to deep-seated solid tumors remains fundamentally constrained by limited light penetration and tumor hypoxia. Endoperoxides (EPOs), which reversibly capture and release ¹O₂, offer a promising strategy to overcome these constraints. Nevertheless, existing EPO-based systems suffer from uncontrolled half-life-dependent ¹O₂ release and inefficient utilization. Moreover, PDT-induced oxidative stress upregulates inducible nitric oxide synthase (iNOS), leading to nitric oxide (NO) overproduction that quenches ¹O₂ and promote adaptive resistance. Herein, we report a self-assembly nano-prodrug enabling on-demand ¹O₂ release while suppressing NO-mediated resistance. An amphiphilic prodrug, L-NARG-SS-Py, comprising a ¹O₂-storing pyridone moiety and an iNOS inhibitor linked via a glutathione-responsive disulfide bond, co-assembles with protoporphyrin IX to form nano-prodrug (PPIX@L-NARG-SS-Py NPs). Upon irradiation, generated ¹O₂ is captured and stored as EPO intermediates, followed by glutathione-triggered release in tumor microenvironment. Simultaneously, released iNOS inhibitor suppresses NO production, thereby reducing ¹O₂ quenching and amplifying oxidative damage. In deep-seated pancreatic tumor models, the nano-prodrug achieves potent tumor suppression with minimal systemic toxicity. This work establishes a biologically amplified, light-independent PDT strategy for overcoming physical and adaptive resistance in deep-tissue phototherapy.

Biodegradable magnesium (Mg) alloy stents offer a transient alternative to permanent metallic implants; however, clinically used WE43 contains rare-earth (RE) elements, raising concerns regarding the long-term biosafety of RE-containing degradation products and their potential tissue accumulation. Here, we investigated two RE-free Mg-Zinc (Zn)-based alloys, MZ01 (Mg-1Zn-0.1Ca) and ZM115 (Mg-1Zn-1.5Mn-0.5Sr), and established a mechanistic cascade linking alloy composition and microstructure to electrochemical analyses revealed alloy-dependent differences in grain structure and interfacial corrosion resistance, with MZ01 exhibiting the highest charge-transfer resistance. In a mouse subcutaneous model, MZ01 showed more uniform degradation, smaller and more rapidly resolving hydrogen gas cavities, and a significantly lower microcrack area fraction at Day 56 than WE43 and ZM115, accompanied by attenuated inflammatory and fibrotic responses. In the rabbit iliac arteries, all stents maintained luminal patency without thrombosis through 56 days, while MZ01 exhibited lower neointimal thickness, lower perivascular apoptosis and late inflammation, and enhanced early endothelialization compared with WE43. Preliminary descriptive porcine coronary implantation further demonstrated the technical feasibility and sustained patency of MZ01 over 56 days. Collectively, these findings define a composition-microstructure-corrosion-cellular response-vascular healing axis and identify MZ01 as a RE-free Mg-Zn alloy with controlled biodegradation and favorable biocompatibility, supporting its further development as a biodegradable cardiovascular scaffold.

Narrow-band ultraviolet B (NB-UVB) phototherapy is clinically regarded as a first-line treatment for moderate-to-severe plaque psoriasis owing to its high tolerance, broad applicability and easy affordability. However, the therapeutic efficacy of short-wave UV light is limited by poor penetration through the thickened stratum corneum of psoriatic skin, whereas excessive NB-UVB irradiation may provoke cutaneous photodamage. Moreover, NB-UVB administration necessitates trained personnel and frequent hospital visits, resulting in poor patient compliance. Here, we developed microneedles with high UV transmittance (UVMNs) to enhance the transdermal delivery efficiency of NB-UVB, thereby reducing the required irradiation dosage and mitigating the risk of photodamage without compromising therapeutic effect. A vitamin D analog, calcipotriol, was further coated onto the UVMN patch to augment the overall efficacy of the phototherapeutic regimen. After insertion into the skin, the calcipotriol is released from the dissolvable coating within minutes to suppress keratinocyte proliferation, followed by UVMN-guided NB-UVB therapy for regulation of regulatory T/T helper 17 cell balance as well as inhibition of keratinocyte proliferation. The integration of phototherapy and topical therapy effectively ameliorated symptoms in a psoriatic mouse model.

Type-I hypersensitivity is a mast cell-mediated degranulation process induced by IgE-antigen recognition. Inspired by this highly specific mechanism, we developed a new cell therapy platform by genetically engineering mouse mast cell line MC/9 to overexpress the cytotoxic proteins perforin and granzyme B (PG-MCs) via lentiviral transduction. In the melanoma model utilizing B16 cells expressing membrane-bound OVA, a polarized degranulation of mast cells towards cancer cells was validated upon the recognition of antigens by anti-OVA IgE. PG-MCs could selectively kill cancer cells via IgE-antigen recognition. The IgE-sensitized PG-MCs administered through an intertumoral route delivered perforin 1 (Prf1) and granzyme B (Gmzb) toward target cells to potentiate anti-tumor efficacy. Moreover, we demonstrated the reprogramming effect of tumor microenvironment by PG-MC-induced hypersensitivity, driving an immune remodeling of the tumor milieu, characterized by the increased lymphocyte infiltration. In addition, this mast cell therapy, in combination with 5- fluorouracil (5-Fu), induced a significant inhibition of tumor growth in a B16-OVA mouse model, which is associated with the depletion of myeloid-derived suppressor cells (MDSCs).

Engineering artificial dendritic cells (DCs) holds great promise for cancer immunotherapy, but achieving spatiotemporally controlled multifunctionality within the immunosuppressive tumor microenvironment remains a challenge. Here, we report a chemically engineered, ultrasound (US)-activatable artificial DCs nanosystem (nDC-M) that mimics the DC-mediated T-cell immunity through a rationally designed molecular assembly. The nDC-M integrates three key functional modules including a semiconducting polymer nanoparticle and interleukin-2 (IL-2) crosslinked by hypoxia-cleavable fragment for on-demand cytokine release upon US trigger, a matured DC membrane cloak for tumor cell recognition and a surface-anchored maleimide (MAL) group for covalent antigen capture and presentation. Under US treatment, sonodynamic effect of semiconducting polymer ablates tumors and consumes oxygen to allow breakage of hypoxia-cleavable fragments, leading to IL-2 leakage. This nDC-M exhibits a comprehensive and conferred mimicking functions including tumor cell recognition, antigen presentation and sono-activatable cytokine secretion. In bilateral breast cancer and lung metastasis models, US-driven nDC-M therapy significantly suppresses tumor progression and metastasis. Moreover, combining nDC-M with checkpoint blockade achieves complete eradication of local and distant tumors and establishes long-term immunological memory against recurrence. This work presents a modular and stimuli-responsive artificial DC platform that integrates chemical synthesis, molecular nanoengineering, and function modulation, offering a versatile strategy for cancer immunotherapy.