An autologous tumor cell-integrated microporous annealed particle scaffold co-delivering an immune adjuvant and an indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor for tumor postoperative therapy is developed, establishing a paradigm that unifies personalized immunotherapy with personalized tissue repair, offering substantial promise for postsurgical cancer therapy.
Abstract
Biomaterial scaffolds hold great potential for addressing tumor recurrence and tissue defects following surgical tumor resection; however, personalized therapy remains a critical barrier to their clinical translation. To address this issue, we developed an autologous tumor cell-integrated microporous annealed particle (MAP) scaffold co-delivering an immune adjuvant and an indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor for tumor postoperative therapy. This scaffold was fabricated using microfluidic electrospray combined with step-by-step crosslinking technology. The injectable microspheres, prior to annealing, can be directly delivered into the defect site and conform to its shape upon crosslinking, forming a stabilized, porous structure. Featuring interconnected pores that facilitate cell infiltration and proliferation, the scaffold demonstrated effective tissue repair in mice subjected to full-thickness skin excision. Within the scaffold, cryo-inactivated tumor cells and the immune adjuvant recruit and activate dendritic cells (DCs) in situ, stimulating a robust antitumor immune response. This response is further amplified by the IDO1 inhibitor, which reverses immunosuppression by inhibiting regulatory T cells (Tregs). Consequently, the scaffold exhibited remarkable anti-recurrence efficacy and prolonged survival in a melanoma mouse model. These properties highlight the significant potential of our personalized microporous hydrogel particle scaffold for efficient postoperative antitumor therapy and tissue regeneration. STATEMENT OF SIGNIFICANCE: Tumor recurrence and tissue defects represent significant challenges following surgical tumor removal in cancer patients. Meanwhile, a critical barrier to the clinical translation of postoperative biomaterial scaffolds is the lack of personalization for both antitumor therapy and tissue reconstruction. Here, we developed a personalized microporous annealed particle (MAP) scaffold that integrates autologous tumor cells, immune adjuvant, and IDO1 inhibitor to simultaneously address tumor recurrence and tissue defects. Personalized antitumor therapy is achieved by the injectable MAP scaffold through a tumor vaccine formed from autologous tumor-derived cells within the scaffold, eliciting tumor-specific T-cell responses that are further amplified by reversing the local immunosuppressive microenvironment. Personalized tissue repair is also enabled by such scaffold, which conforms to irregular wound shapes and supports cell infiltration. This work establishes a paradigm that unifies personalized immunotherapy with personalized tissue repair, offering substantial promise for postsurgical cancer therapy.
In vivo animal experiments show that the drug-loaded scaffold significantly inhibits tumor recurrence and distant metastasis while exhibiting low chemotherapy drug toxicity and causing no damage to healthy tissues, making it a novel candidate for post-mastectomy prognosis in breast tumors and effective cancer treatment.
Jiaqi Chen, Hanliu Gu, Ziqi Wang et al.· Journal of Materials Science· 0 citations
One of the main issues in oncology is tumor recurrence following resection, which is responsible for a large number of patient deaths and treatment failures in a variety of malignancies. Despite advancements in adjuvant chemotherapy and radiation, residual disease that remains inside or close to the resection cavity and is difficult for systemic therapies to eradicate is the cause of further local recurrence. Hydrogel-nanoparticle (HNP) composites are a new class of therapeutic platforms that emerged from the recent convergence of biomaterial science and nanomedicine. Their specific goals are to fill the surgical gap, provide long-term localized drug release, and energetically remodel the post-surgical tumor microenvironment (TME). This paper includes the biological foundations of localized post-surgical therapy, important physicochemical considerations of the hydrogel matrix and nanoparticle carrier design, and a compilation of mechanistic and preclinical evidence for HNP hybrid platforms. Immunomodulatory strategies, stimuli-responsive release mechanism engineering, and novel techniques, including combination immunotherapy and 3D-printed customized scaffolds, are all given special attention. Examples of translational challenges are also addressed, such as manufacturing repeatability, biocompatibility, and regulatory classification. When considered collectively, the data demonstrate that HNP platforms are a convincing, practically feasible approach to reducing post-surgical recurrence rates and enhancing patient outcomes.
Bogdan Mircea Măciuceanu Zărnescu, Denisa Nicoleta Mușat, Adelina-Gabriela Niculescu et al.· Nanomaterials· 2 citations
Biomimetic technology has high potential for enhancing cancer immunogene therapy. Cell membrane-coated nanoparticles (CMNPs) obtain extra targeting, recognition, and signaling transduction functions. However, a single kind of CMNPs is limited when facing complicated tumor immunogene therapy. Here reported the collaboration of two types of CMNPs using a double-layered spherical scaffold. This scaffold was prepared by stacking photosensitive hydrogels with two concentrations. After implantation, the two layers degraded successively within 5-8 days, enabling sequential and controlled release of payloads. Based on this, a MG-709 double-layered formulation which co-delivered cancer cell membrane-coated nanoparticle/siRNA complex (siStat3@CMP) in the outer layer, and DC membrane-coated nanoparticle/cancer cell lysate complex (DMLD) in the inner layer. The results demonstrated that siStat3@CMP was released first and exerted its apoptosis-inducing effect, resulting in the release of tumor-associated antigens (TAAs). Subsequently, TAAs as well as immune cells migrated into the inner layer, where they worked together with DMLD to ignite immune responses. The activated immune cells were then released to perform immunotherapeutic effects. Facilitated by this mechanism, in situ implantation of the MG-709 scaffold efficiently suppressed the development of multiple colorectal cancer models. The study provides a new solution for the collaboration of CMNPs in tumor immunogene therapy.
Jingmei Li, Jin Zhang, Xia-Yu Chen et al.· Small· 0 citations
Overall, the most clinically realistic direction is a staged and adaptable platform that provides early local tumor control while progressively supporting bone regeneration and structural reconstruction.
Xiaonan Wang, Aobo Zhang· International Journal of Bio...· 0 citations
Resection of bone-metastatic tumors is often accompanied by severe bone erosion and structural defects. Three‐dimensional (3D) printed hydrogel scaffolds with tailorable architectures and mechanical robustness are increasingly employed to restore bone integrity after tumor removal. Here, a 3D-printed sodium alginate/GelMA hydrogel scaffold is engineered to remodel the local microenvironment for simultaneous tumor ablation and bone repair, aiming to overcome the persistent challenge of functionally modifying hydrogel scaffolds to achieve both effective tumor eradication and bone regeneration. The scaffold encapsulates dendritic cell-derived exosomes loaded with the STING agonist Cyclic dinucleotide (Dex-CDN), together with methacrylated osteogenic growth peptide (OGP-MA), while a dopamine–manganese coordination nanozyme (DM) forms a mussel‐inspired catalytic coating on the surface. Under the acidic tumor milieu, DM exhibits peroxidase‐like activity to trigger Fenton reactions, deplete glutathione, and induce oxidative stress–mediated tumor cell death. Under physiological conditions, DM displays superoxide dismutase‐ and catalase‐like activities, scavenging reactive oxygen species and maintaining redox homeostasis to promote osteogenesis. Sustained Dex‐CDN release activates STING signaling and elicits potent antitumor immunity, whereas OGP‐MA triggers BMP/Smad‐mediated osteogenic differentiation. This integrated scaffold unites catalytic therapy, immune activation, and osteoinduction, offering a promising strategy for localized tumor control and bone regeneration following bone metastatic tumor resection.
Jiachen He, Jianjun Wu, Lin Wang et al.· Advanced Composites and Hybr...· 0 citations
Radiotherapy initiates an antitumor immune response by releasing tumor antigens; however, its efficacy is often limited by the subsequent quantitative and qualitative dysfunction of dendritic cells within the tumor microenvironment. This dysfunction leads to impaired antigen presentation and suboptimal T cell activation. To address this, we developed a biomaterial-based cellular engineering strategy using silk fibroin-based dendritic cell backpacks. Silk fibroin backpacks offer structural stability and aqueous processability, enabling the incorporation of CpG under mild conditions. The easy functionalization of silk fibroin allows hydrophobic modifications on the backpack surface, enabling covalent grafting of hydrophobic chains onto the BP surface and promoting stable association with the DC membrane through hydrophobic intercalation. These backpacks preserve dendritic cell function while providing sustained local delivery of immune signals. This platform integrates material design with cellular immunoengineering to overcome a key barrier in post-radiation immunity, presenting a versatile strategy to enhance dendritic cell function and synergize with radiotherapeutic modalities for more durable antitumor immunity.
Xuying Hu, He Liu, Yixu Yin et al.· Biomaterials Advances· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
