Inhalable nanovesicles loaded with a STING agonist enhance CAR-T cell activity against solid tumors in the lung

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 2, 2025

Suppression of chimeric antigen receptor-modified T (CAR-T) cells by the immunosuppressive tumor microenvironment remains a major barrier to their efficacy against solid tumors. To address this, we develop an anti-PD-L1-expressing nanovesicle loaded with STING agonist cGAMP (aPD-L1 NVs@cGAMP) remodel and thereby enhance CAR-T cell activity. Following pulmonary delivery, nanovesicles rapidly accumulate in lung selectively deliver agonists PD-L1-overexpressing via PD-1/PD-L1 interaction. This targeted delivery effectively avoids systemic inflammation poor cellular uptake that plague free agonists. Internalized trigger signaling induce interferon responses, which diminish populations such as myeloid-derived suppressor promote infiltration. Importantly, anti-PD-L1 single chain variable fragment on surface blocks PD-L1 upregulation induced prevents exhaustion. In both orthotopic cancer metastasis model, combined therapy aPD-L1 NVs@cGAMP potently inhibits growth recurrence. Therefore, is expected serve effective enhancer improve The hindered Here authors report design characterization inhalable cGAMP, showing enhanced activity models.

Язык: Английский

---

Therapeutic role of immune cells against colon cancer

Elsevier eBooks, Год журнала: 2025, Номер unknown, С. 127 - 146

Опубликована: Янв. 1, 2025

Язык: Английский

---

Designed Biomaterial‐Enhanced Cell Transplantation for Neural Tissue Engineering

Aggregate, Год журнала: 2025, Номер unknown

Опубликована: Март 7, 2025

ABSTRACT Cell transplantation therapy in the central nervous system is hindered by limited survival and integration of grafted cells. Biomaterials have emerged as an attractive solution to this problem providing a protective microenvironment deliver cells injured tissues. The design biomaterials compatible with tissues promote tissue repair functional recovery focus neural engineering. A wealth research has explored different materials architectures combination bioactive cues glial cell growth maturation. After brief presentation biomaterial strategies sources, we review vivo evidences about efficacy stem cotransplantation (i) enhancing trophic effects, (ii) increasing integration, (iii) achieving preclinical models stroke, traumatic brain injury, Parkinson's disease, spinal cord injury. Furthermore, comprehensive perspective was offered regarding specific implementation tactics, obstacles, development orientations employing critical support transplantation.

Язык: Английский

---

Artificially Tagging Tumors with Nano-Aluminum Adjuvant-Tethered Antigen mRNA Recruits and Activates Antigen-Specific Cytotoxic T Cells for Enhanced Cancer Immunotherapy

Biomaterials, Год журнала: 2025, Номер 317, С. 123085 - 123085

Опубликована: Янв. 5, 2025

T cell therapy for solid tumors faces significant challenges due to the immune off-target attack caused by loss of tumor surface antigens and inactivation in acidic microenvironment (TME). Herein, we developed a bifunctional immunomodulator (MO@NAL) loading ovalbumin (OVA; model antigen) mRNA (mOVA) onto lysozyme-coated layered double hydroxide nano-aluminum adjuvant (NA). The NA's inherent alkalinity effectively neutralizes excess acid within TME suppresses regulatory cells, creating favorable enhance cytotoxic infiltration activation tumors. Particularly, once internalization MO@NAL efficiently tags with OVA through carried mOVA, providing targets recruiting directing antigen-specific cells destroy cells. In mice pre-vaccinated vaccine, intratumoral administration rapidly awakens OVA-specific memory, inhibiting progression colon melanoma at both early advanced stages. non-pre-vaccinated mice, combining therapeutic vaccine or adoptive transfusion similarly achieves robust suppression. These findings thus underscore potential as an effective safe enhancing responses timely intervention progression.

Язык: Английский

---

Innovative Approaches to Boost Mesenchymal Stem Cells Efficacy in Myocardial Infarction Therapy

Materials Today Bio, Год журнала: 2025, Номер 31, С. 101476 - 101476

Опубликована: Янв. 9, 2025

Stem cell-based therapy has emerged as a promising approach for heart repair, potentially regenerating damaged tissue and improving outcomes patients with disease. However, the efficacy of stem therapies remains limited by several challenges, including poor cell survival, low retention rates, integration, functional outcomes. This article reviews current enhancement strategies to optimize mesenchymal cardiac repair. Key approaches include optimizing delivery methods, enhancing engraftment, promoting functions through genetic molecular modifications, paracrine effects cells, leveraging biomaterials engineering techniques. By focusing on these techniques, paper highlights innovative that can transform into more viable effective treatment option The ongoing research technological advancements continue push boundaries, hoping make mainstream

Язык: Английский

---

Supramolecular peptide hydrogel epitope vaccine functionalized with CAR-T cells for the treatment of solid tumors

Materials Today Bio, Год журнала: 2025, Номер 31, С. 101517 - 101517

Опубликована: Янв. 22, 2025

Chimeric antigen receptor T-cell (CAR-T) therapy, which benefits from the perfect combination of gene editing techniques and antibody engineering, has shown outstanding clinical efficacy in hematological malignancies. Solid tumors present next challenge due to their extremely complicated microenvironment structural characteristics. Targeting efficiency persistence are currently bottleneck issues treatment CAR-T. Beyond drugs cytokines, biomaterials can modulate immune response, assisting adoptive CAR-T cells exerting function. In this study, a supramolecular peptide hydrogel epitope vaccine was designed serve as both preparation medium reservoir for cells. The self-assembling formed nanofiber scaffold through non-covalent interactions amphiphilic amino acids ion stabilizers. Firstly, complementary conjugated epitopes target sites were derived different extracellular domains HER2 protein, improved tumor spreading targeting efficiency. promoted cell proliferation, cytotoxic activity, lymphocyte subpopulation transformation. Furthermore, encapsulated (SPEV-CAR-T) induced endogenous humoral cellular responses sustained release cells, demonstrating superior anti-tumor effects an vivo mouse model. Most importantly, SPEV-CAR-T central memory systemic tissues, addressing poor single therapy. integration complementation active passive all-in-one system facilitated sequential succession exogenous responses, promoting persistent specific attack. showed therapeutic solid tumors.

Язык: Английский

---

Delivering living medicines with biomaterials

Nature Reviews Materials, Год журнала: 2025, Номер unknown

Опубликована: Янв. 27, 2025

Язык: Английский

---

Dual-Responsive Alginate/PNIPAM Microspheres Fabricated by Microemulsion-Based Electrospray

Polymers, Год журнала: 2024, Номер 16(19), С. 2765 - 2765

Опубликована: Сен. 30, 2024

Smart materials for drug delivery are designed to offer a precise and controlled release of therapeutic agents. By responding specific physiological stimuli, such as changes in temperature pH, these improve treatment efficacy minimize side effects, paving the way personalized solutions. In this study, we present fabrication dual-responsive alginate/poly(N-isopropylacrylamide) (PNIPAM) microspheres, having ability respond both pH variations embedding lipophilic bioactive compound Ozoile. Ozoile® Stable Ozonides is obtained from extra virgin olive oil acts an inducer, interacting with major biological pathways by means modulating systemic redox balance. The microspheres prepared electrospray technique without use organic solvents. PNIPAM synthesized radical polymerization using APS/TEMED initiators. further optimized chitosan coating enhance their stability modulate degradation kinetics gel matrix. A comprehensive morphological analysis, Fourier transform infrared (FTIR) spectroscopy, assays conducted confirm structural pH-responsive behavior hydrogel microspheres. study volume phase transition (VPTT) differential scanning calorimetry (DSC) used assess microsphere thermal response. This research introduces promising methodology development targeted systems, which particularly useful context oxidative stress modulation inflammation management.

Язык: Английский

---

Implantable Biomaterials for Cancer Immunotherapies

Advanced Functional Materials, Год журнала: 2024, Номер unknown

Опубликована: Дек. 9, 2024

Abstract Cancer immunotherapy has revolutionized cancer treatment by leveraging the immune system to target and eliminate tumor cells. Implantable biomaterials, such as hydrogels, sponges, scaffolds, implantable microdevice platforms, macrobeads, offer localized sustained release of immunomodulatory agents, improving delivery treatments checkpoint inhibitors, vaccines, adoptive cell therapies like CAR‐T This review examines emerging role these biomaterials in modulating microenvironment, enhancing recruitment, reducing systemic side effects, positioning them significant tools for treating solid tumors. Recent advances material engineering are also discussed, including integration bioactive molecules real‐time therapeutic adjustments based on patient‐specific responses, which new potential personalized treatments. However, challenges biocompatibility, high production costs, variability patient response, necessity surgical manipulations remain key obstacles. Nonetheless, ongoing research technological advancements steadily addressing issues, paving way more effective accessible immunotherapies. Overall, this highlights promise overcoming current limitations expanding scope effective, targeted

Язык: Английский

---

Biomaterials Enhancing Localized Cancer Therapy Activated Anti-Tumor Immunity: A Review

Journal of Materials Chemistry B, Год журнала: 2024, Номер 13(1), С. 117 - 136

Опубликована: Ноя. 6, 2024

This article reviews the application of biomaterials in combination with immunotherapy to enhance localized treatment tumors, along current challenges and future development directions this field.

Язык: Английский

---