Microenvironment-responsive nanomedicines: a promising direction for tissue regeneration

Military Medical Research, Год журнала: 2024, Номер 11(1)

Опубликована: Окт. 21, 2024

Abstract Severe tissue defects present formidable challenges to human health, persisting as major contributors mortality rates. The complex pathological microenvironment, particularly the disrupted immune landscape within these defects, poses substantial hurdles existing regeneration strategies. However, emergence of nanobiotechnology has opened a new direction in immunomodulatory nanomedicine, providing encouraging prospects for and restoration. This review aims gather recent advances nanomedicine foster regeneration. We begin by elucidating distinctive features local microenvironment defective tissues its crucial role Subsequently, we explore design functional properties nanosystems. Finally, address clinical translation development, aiming propose potent approach enhance through synergistic modulation integration.

Язык: Английский

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Investigating the delivery of PD-L1-targeted immunoliposomes in a dynamic cervical cancer-on-a-chip model

Journal of Controlled Release, Год журнала: 2025, Номер 379, С. 236 - 250

Опубликована: Янв. 11, 2025

The recent approval of pembrolizumab in recurrent or metastatic cervical cancer warrants further investigations into the usefulness immunotherapies for more durable and less radical interventions. In this study, targeting potential anti-PD-L1-functionalized immunoliposomes was tested a 3D vitro cancer-on-a-chip model. Immunolipsomes were synthesized decorated externally with monovalent anti-PD-L1 Fab' fragments commercially available atezolizumab. Cervical cell lines varying levels PD-L1 expression cultured as spheroids embedded collagen I matrix, treated under flow culture media. Flow cytometry live-cell confocal imaging used to measure interactions uptake untargeted liposomes panel lines. retained specific functionality regardless protein corona formation high serum environments. As such, expressing preferentially internalized environment extracellular matrix present, while low PD-L1-expressing showed no preference either formulation. Importantly, treatments performed monolayer cultures (on plastic) differences between immuno- liposome uptake, including way which endocytosed are trafficked subcellularly. This study demonstrates importance both active passive accumulation strategies achieve nanoparticle targeting. Immunoliposomes remain promising platform development targeted nanotherapies against cancers. However, initial functional tests did not translate directly biological performance should be kept mind future formulations. Furthermore, model developed appeared useful visualizing 3D, live tissue represents cost-effective reproducible studies.

Язык: Английский

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Interrogation of the Tumor Microenvironment by Nanoparticles

Cancer Letters, Год журнала: 2025, Номер unknown, С. 217454 - 217454

Опубликована: Янв. 1, 2025

Язык: Английский

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TCR-T cell therapy for solid tumors: challenges and emerging solutions

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Март 10, 2025

With the use of T cell receptor cells (TCR-T cells) and chimeric antigen (CAR-T cells), T-cell immunotherapy for cancer has advanced significantly in recent years. CAR-T therapy demonstrated extraordinary success when used to treat hematologic malignancies. Nevertheless, there are several barriers that prevent this achievement from being applied solid tumors, such as challenges with tumor targeting inadequate transit adaption genetically modified T-cells, especially unfavorable microenvironments The deficiencies treatment tumors compensated by TCR-T cells, which have a stronger homing ability initiate intracellular commands, 90% proteins can be developmental targets, they recognize target antigens more broadly. As result, may effective treating tumors. In review, we discussed structure outlined drawbacks therapy, suggested potential remedies. This review is crucial understanding current state future therapy. We emphasize how important it combinatorial approaches, combining new combinations various emerging strategies over-the-counter therapies designed TCR-T, increase anti-tumor efficacy inside TME maximize safety, comes immunotherapies.

Язык: Английский

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Optimizing CAR-T cell therapy for solid tumors: current challenges and potential strategies

Journal of Hematology & Oncology, Год журнала: 2024, Номер 17(1)

Опубликована: Ноя. 5, 2024

Chimeric antigen receptor (CAR)-T cell therapy demonstrates substantial efficacy in various hematological malignancies. However, its application solid tumors is still limited. Clinical studies report suboptimal outcomes such as reduced cytotoxicity of CAR-T cells and tumor evasion, underscoring the need to address challenges sliding cells. Despite improvements from fourth next-generation cells, new include systemic toxicity continuously secreted proteins, low productivity, elevated costs. Recent research targets genetic modifications boost killing potential, metabolic interventions hinder progression, diverse combination strategies enhance therapy. Efforts reduce duration cost developing allogenic in-vivo approaches, promising significant future advancements. Concurrently, innovative technologies platforms potential overcome limitations treating tumors. This review explores optimize therapies for tumors, focusing on enhancing overcoming restrictions. We summarize recent advances T subset selection, structural modifications, infiltration enhancement, interventions, production optimization, integration novel technologies, presenting therapeutic approaches that could improve therapy's applicability

Язык: Английский

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High-Throughput In Vivo Screening Identifies Differential Influences on mRNA Lipid Nanoparticle Immune Cell Delivery by Administration Route

ACS Nano, Год журнала: 2024, Номер 18(25), С. 16151 - 16165

Опубликована: Июнь 11, 2024

Immune modulation through the intracellular delivery of nucleoside-modified mRNA to immune cells is an attractive approach for in vivo immunoengineering, with applications infectious disease, cancer immunotherapy, and beyond. Lipid nanoparticles (LNPs) have come fore as a promising nucleic acid platform, but LNP design criteria remain poorly defined, making rate-limiting step discovery screening process. In this study, we employed high-throughput based on molecular barcoding investigate influence composition tropism vaccines systemic immunotherapies. Screening large library under both intramuscular (i.m.) intravenous (i.v.) injection, observed differential influences uptake by populations across two administration routes, gleaning insight into immunoengineering. validation studies, lead formulation i.m. demonstrated substantial translation spleen draining lymph nodes more favorable biodistribution profile than LNPs formulated clinical standard ionizable lipid DLin-MC3-DMA (MC3). The formulations i.v. displayed potent transfection peripheral blood, one demonstrating splenic dendritic another inducing circulating monocytes. Altogether, immunotropic identified significant promise locally- systemically-delivered confirmed value gleaned from our process, which could potentially inform future endeavors vaccine immunotherapy applications.

Язык: Английский

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CAR-T cell combination therapies in hematologic malignancies

Experimental Hematology and Oncology, Год журнала: 2024, Номер 13(1)

Опубликована: Июль 18, 2024

Abstract Chimeric antigen receptor-T cell therapy, a groundbreaking cancer treatment, has achieved remarkable success against hematologic malignancies. However, CAR-T monotherapy faces challenges in certain cases, including treatment tolerance and relapse rates. To overcome these challenges, researchers are investigating combining cells with other treatments to enhance therapeutic efficacy. Therefore, this review aims investigate the progress of research for It covers basic principles clinical applications detailing combinations chemotherapy, immune checkpoint inhibitors, targeted drugs, radiotherapy, hematopoietic stem transplantation, treatments. These synergistically antitumor effects comprehensively target tumors through different mechanisms, improving patient response survival

Язык: Английский

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mRNA Lipid Nanoparticles for Ex Vivo Engineering of Immunosuppressive T Cells for Autoimmunity Therapies

Nano Letters, Год журнала: 2023, Номер 23(22), С. 10179 - 10188

Опубликована: Окт. 31, 2023

Cell-based therapies for autoimmune diseases have gained significant traction, with several approaches centered around the regulatory T (Treg) cell─a well-known immunosuppressive cell characterized by its expression of transcription factor Foxp3. Unfortunately, due to low numbers Treg cells available in circulation, harvesting and culturing remains a challenge. It has been reported that engineering Foxp3 CD4+ can result Treg-like phenotype; however, current methods inefficient these cells. Here, we develop an ionizable lipid nanoparticle (LNP) platform effectively deliver mRNA We successfully engineer into Foxp3-T (FP3T) transiently exhibit phenotype functionally suppress proliferation effector These results demonstrate promise LNP potential applications autoimmunity therapies.

Язык: Английский

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mRNA‐based chimeric antigen receptor T cell therapy: Basic principles, recent advances and future directions

Deleted Journal, Год журнала: 2023, Номер 2(1)

Опубликована: Дек. 29, 2023

Abstract Non‐viral vector chimeric antigen receptor (CAR)‐T cells have garnered increasing attention due to their ability efficiently eradicate cancer while mitigating undesirable side effects. However, the current methods for engineering T (CAR‐T) employ viral vectors that result in permanent CAR expression and potentially severe negative impacts. As a solution these challenges, triggering transitory of CARs via messenger RNA (mRNA) has emerged as promising strategy. Currently, electroporation is common method used introduce mRNA encoding into cells. Moreover, there been on exploration innovative delivery systems, including lipid, polymer‐based nanoparticle, exosomes peptide transduction domains. Additionally, we also explored functions different types mRNA‐based CAR‐T cell therapy. The auxiliary mRNA, exemplified by systems such megaTAL nuclease transposon demonstrates its capacity extend viability survival. This perspective offers state therapy provides valuable insights future research avenues.

Язык: Английский

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Current Advancements in Anti-Cancer Chimeric Antigen Receptor T Cell Immunotherapy and How Nanotechnology May Change the Game

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(10), С. 5361 - 5361

Опубликована: Май 14, 2024

Chimeric antigen receptor (CAR)-T cell immunotherapy represents a cutting-edge advancement in the landscape of cancer treatment. This innovative therapy has shown exceptional promise targeting and eradicating malignant tumors, specifically leukemias lymphomas. However, despite its groundbreaking successes, is not without challenges. These challenges, particularly pronounced treatment solid include but are limited to, selection appropriate tumor antigens, managing therapy-related toxicity, overcoming T-cell exhaustion, addressing substantial financial costs associated with Nanomedicine, an interdisciplinary field that merges nanotechnology medical science, offers novel strategies could potentially address these limitations. Its application already led to significant advancements, including improved specificity drug targeting, advancements diagnostics, enhanced imaging techniques, for long-term prevention. The integration nanomedicine revolutionize by enhancing delivery genes engineering, reducing systemic alleviating immunosuppressive effects within microenvironment. review aims explore how far come alone, strengthen it into future. Additionally, will examine limit off-target toxicity therapy, patient tolerance outcomes.

Язык: Английский

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