Biomaterials research最新文献

[This corrects the article DOI: 10.34133/bmr.0208.].

The management of medulloblastoma (MB) remains a significant challenge, primarily attributed to the presence of cancer stem cells and the inadequate delivery of therapeutic agents across the blood-brain barrier. GLI, as a regulator of the hedgehog signaling pathway in normal cerebellum development, also exerts pivotal functions in MB initiation, progression, and metastasis and maintains the stemness of MB stem cells. In this study, we devised a combined therapeutic approach by integrating the BRD4 inhibitor JQ1 with the SMO inhibitor saikosaponin B1 (SSB1) to inhibit MB via regulation of GLI activation. The results suggested that JQ1 and SSB1 synergistically inhibited MB proliferation, constricted MB metastasis, and down-regulated stem cell phenotypes via reduced GLI and MYC expression. Tryptamine-derived lipid nanoparticles (NPs) transported JQ1 and SSB1 to MB tissues. The targeted NPs demonstrated prolonged drug release kinetics and significantly improved their accumulation in MB tumors. Systemic administration of drug-loaded targeted NPs significantly decreased tumor burden without hepatic toxicity in xenograft MB-bearing mice. The combination of JQ1 and SSB1 presents an innovative therapeutic paradigm for suppressing MB proliferation, recurrence, and metastasis, with the potential to drive the development of novel MB treatment strategies in the future.

The combination of chemical immunotherapy and gene therapy holds great promise for malignant tumor treatment. Here, we developed an ultrasound-targeted liposome nanobubbles system (NKP-1339/miR-142-NBs) for precise codelivery of drugs and genes to treat esophageal squamous cell carcinoma (ESCC) with ultrasound-targeted microbubble destruction (UTMD). This study systematically investigated the system's therapeutic mechanisms-including mitochondrial dysfunction induction, immunogenic cell death (ICD), and antitumor immune activation-alongside its pharmacokinetics and targeting efficiency. In an ESCC mouse model, NKP-1339/miR-142-NBs combined with ultrasound markedly suppressed tumor growth (79.72% ± 0.1% vs. NB control 18.79% ± 1.29%) through NKP-1339 triggering ICD and miR-142-5p down-regulating programmed death-ligand 1 (PD-L1) expression, synergistically potentiating immune responses. Furthermore, we found that triggering ICD, including the exposure of calreticulin on the cell membrane, was related to altering mitochondrial fission dynamics in the ESCC cells. The down-regulation of PD-L1 expression by miR-142-5p reactivated CD8⁺ T cells by relieving programmed death-1 (PD-1)/PD-L1-mediated immunosuppression, enhancing immune memory and antitumor efficacy. Moreover, the UTMD technique enhanced the tumoral accumulation and penetration of nanobubbles, improving delivery specificity and minimizing off-target effects. This combined treatment strategy, including UTMD, provides a promising translational potential for ESCC therapy.

Viral pneumonia poses a major global public health challenge, where excessive inflammatory responses contribute to tissue damage and respiratory failure. Inflammation-responsive nanoparticles can target inflamed areas, improving drug delivery while minimizing side effects. Chitosan, a biocompatible polysaccharide with anti-inflammatory and immunomodulatory properties, gains enhanced antioxidant and anti-inflammatory capabilities when combined with selenium. This study developed selenium-chitosan nanoparticles loaded with Moringa A (MA), a natural antiviral compound from Moringa oleifera seeds. These nanoparticles target lung inflammation, releasing MA to suppress viral replication and infection while reducing inflammatory responses. Additionally, selenium-chitosan nanoparticles mitigate oxidative stress, regulate immunity, and inhibit PANoptosis-a cell death pathway that exacerbates inflammation. By blocking core proteins in this pathway, they further curb inflammatory factor release. This approach offers a promising therapeutic strategy for viral pneumonia, combining targeted drug delivery, antiviral action, and inflammation control with reduced side effects.

Peripheral nerve injury is a common health issue in modern aging societies, with the only treatment available being autograft transplantation. Unfortunately, autograft is often limited due to donor availability and immune rejection. Additionally, the peripheral nervous system has limited regenerative capacity, making the treatment of peripheral nerve injuries challenging. Metal-based regenerative medicine and tissue engineering strategies provide advanced solutions to the problem. Metal-based biomaterials such as conduits, filaments, alloys, hydrogels, and ceramics can deliver biofunctional metal ions and promote axonal growth and functional recovery. In parallel, metal-based electromagnetic stimulation demonstrates potential for nerve regeneration and inflammation regulation. The potential of metal-based biomaterials in promoting peripheral nerve regeneration highlights the need for further research in tissue engineering and regenerative medicine. However, rapid degradation, long-term biocompatibility, and necessary optimization regarding injury types remain to be explored. This review summarizes the reported metal-based biomaterials utilized in peripheral nerve regeneration research. The aim is to showcase advanced technologies available in the field, which may potentially become a viable alternative to autografts, offering transformative applications in the regenerative medical field.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection has been associated with severe cardiovascular complications. However, the role of epitranscriptional modulation involved in SARS-CoV-2-infected myocarditis is still unclear. Ten-eleven translocation 2 (TET2), a methylcytosine dioxygenase, plays key roles in DNA demethylation during viral infection and host-virus interactions. Using human-induced-pluripotent-stem-cell-derived cardiomyocytes (hiPSC-CMs) as a platform, our data revealed the epitranscriptomic role of TET2 during SARS-CoV-2 infection. First, our RNA sequencing analysis revealed the alterations of the messenger-RNA-expression profiles of epitranscriptomic regulators, including TET2, in hiPSC-CMs during SARS-CoV-2 infection. Second, silencing TET2 markedly reduced both the messenger RNA and protein levels of the viral nucleocapsid (N) protein, leading to attenuated viral replication in infected hiPSC-CMs. Furthermore, RNA dot-blotting analysis revealed that TET2 knockdown suppressed the levels of 5-hydroxymethylcytosine in SARS-CoV-2-infected hiPSC-CMs. To further explore the therapeutic relevance of TET2 inhibition in suppressing SARS-CoV-2 infection, we screened and compared 3 structurally distinct TET2 enzymatic inhibitors: Bobcat339, TETi76, and TFMB-2HG. Among these, Bobcat339 demonstrated the most potent antiviral effect, markedly suppressing SARS-CoV-2 replication and N-protein expression. Molecular docking analysis revealed that Bobcat339 exhibited a high binding affinity for multiple viral targets, including nsp16, RdRp, and N protein, indicating a multitarget mechanism of action. In addition, our data demonstrated that treatment with Bobcat339 can suppress SARS-CoV-2 infectious activity and N-protein expression in infected hiPSC-CMs. Together, our findings highlight the regulatory role of TET2 in SARS-CoV-2 infection and identify Bobcat339 as a promising therapeutic compound. Understanding TET2-driven epitranscriptomics and the functions of TET-targeting inhibitors may provide a novel strategy for mitigating viral infection in SARS-CoV-2-induced cardiomyopathy.

Keloids are pathological scars characterized by excessive proliferation of fibroblasts and abnormal extracellular matrix (ECM) accumulation, largely mediated by transforming growth factor-β1 (TGF-β1). Current therapeutic approaches often fail due to high recurrence and limited selectivity. Here, we investigate the potential of human hair-derived keratin (HK) as a biomaterial with selective anti-fibrotic activity. Using multiple in vitro models including 2D monolayers, 3D spheroids, fibroblast-keratinocyte coculture, and collagen gel contraction, we evaluated the effects of 0.5% HK on keloid fibroblasts (KFs) and normal dermal fibroblasts (DFs), with and without TGF-β1 stimulation. HK selectively inhibited KF proliferation, viability, and migration while sparing DF. In 3D models, HK significantly reduced KF-mediated spheroid expansion and collagen matrix contraction, even under profibrotic stimulation. Mechanistically, HK activated intrinsic apoptotic signaling, up-regulating pro-apoptotic proteins (Bax, caspase-3, CYCS) and down-regulating Bcl-2 and XIAP. Transcriptomic profiling revealed that HK down-regulated pathways associated with ECM-receptor interaction, focal adhesion, and aminoacyl-tRNA biosynthesis in KF, suggesting a dual modulation of fibrotic remodeling and mitochondrial function. These findings demonstrate that HK exerts selective anti-fibrotic and pro-apoptotic effects on pathological fibroblasts, with minimal impact on normal cells. By modulating both ECM organization and cell survival pathways, keratin demonstrates strong potential as a therapeutic biomaterial for targeted keloid treatment.

Photodynamic therapy (PDT) is a promising cancer treatment modality due to its minimally invasive nature and spatiotemporal selectivity. However, its effectiveness is substantially hindered by tumor hypoxia. In this study, bismuth vanadate/molybdenum disulfide@hyaluronic acid (BiVO₄/MoS₂@HA, BM@HA) nanoparticles were engineered to overcome the challenges of tumor hypoxia in PDT. The formation of p-n heterojunctions between MoS₂ and BiVO₄ facilitated electron transfer from MoS₂ to BiVO₄, imparting BM@HA with photothermal properties in the near-infrared (NIR) region and achieving an improved photothermal efficiency of 51.9%. After 808-nm laser irradiation, the electron transfers and the energy generated by photothermal effects enhanced the separation of electron-hole pairs in BM@HA, leading to the production of reactive oxygen species and the hydrolysis of oxygen. Animal experiments revealed the strong tumor-targeting capability of BM@HA, as shown by tumor photothermal imaging and in vivo small-animal imaging. Following 808-nm laser irradiation, it enabled precise tumor phototherapy by combining PDT with photothermal therapy. Furthermore, proteomic analysis revealed that BM@HA + NIR may induce necroptosis of tumor cells by activating peptidylprolyl isomerase D-related pathways. In summary, the BM@HA photosensitizer facilitated NIR photocatalytic oxygen hydrolysis, overcoming the hypoxia limitation in PDT. When combined with photothermal therapy, it displayed improved antitumor efficacy, offering a new strategy for the treatment of oral squamous cell carcinoma.

Immune checkpoint inhibitors (ICIs) have successfully transformed clinical oncology against various cancers. However, their widespread utility is limited by low response rates and severe adverse events; thus, a safe and effective approach is required to address these issues. Here, we report the nanoengineering of an anti-programmed cell death-1 antibody (aPD-1) to boost the therapeutic effects following direct local administration into tumors. Specifically, we prepared an aPD-1 nanoformulation using biocompatible mesoporous polydopamine nanoparticles (MPNs) that allow facile and efficient surface functionalization of aPD-1 via latent reactivity to proteins. The nanoformulation increased the antagonistic activity of aPD-1 against PD-1 receptors by enhancing their avidity interactions, effectively blocking PD-1 immune checkpoint signaling in T cells to restore their activation and effector function. The nanoformulation administered via local intratumoral injection enhanced tumor retention of aPD-1 and elicited strong antitumor efficacy against local tumors and long-term tumor recurrence. Our results indicate that robust immune checkpoint signaling blockade in the local tumors using nano-ICI treatment can effectively orchestrate antitumor immunity for local and systemic cancer treatment. Overall, this study underscores the potential of a biomaterial-based nanoengineering approach for improving the efficacy and safety of antibody-based ICI therapy with localized tumor treatment.