Regulatory insights into nanomedicine and gene vaccine innovation: Safety assessment, challenges, and regulatory perspectives

Acta Biomaterialia, Год журнала: 2024, Номер 180, С. 1 - 17

Опубликована: Апрель 10, 2024

This analysis explores the principal regulatory concerns linked to nanomedicines and gene vaccines, including complexities involved perspectives on how navigate them. In realm of nanomedicines, ensuring safety nanomaterials is paramount due their unique characteristics potential interactions with biological systems. Regulatory bodies are actively formulating guidelines standards assess risks associated nanomedicine products, emphasizing need for standardized characterization techniques accurately gauge effectiveness. Regarding frameworks must be tailored address distinct challenges posed by genetic interventions, necessitating special considerations in efficacy evaluations, particularly concerning vector design, target specificity, long-term patient monitoring. Ethical such as autonomy, informed consent, privacy also demand careful attention, alongside intricate matter intellectual property rights, which balanced against imperative widespread access these life-saving treatments. Collaborative efforts among bodies, researchers, patent offices, private sector essential tackle effectively, international cooperation being especially crucial given global scope vaccine development. Striking right balance between safeguarding properties promoting public health vital fostering innovation equitable ground-breaking technologies, underscoring significance addressing hurdles fully harness benefits vaccines enhancing healthcare outcomes a scale. STATEMENT OF SIGNIFICANCE: Several biomaterials proposed development nanovaccines, from polymeric micelles, PLGA-/PEI-/PLL-nanoparticles, solid lipid nananoparticles, cationic lipoplexes, liposomes, hybrid materials, dendrimers, carbon nanotubes, hydrogels, quantum dots. Lipid nanoparticles (LNPs) have gained tremendous attention since US Food Drug Administration (FDA) approval Pfizer Moderna's COVID-19 raising awareness vaccines. review provides insights into current strategies issues, clinical trials. By navigating landscapes we can unlock full using range promising towards improving worldwide.

Язык: Английский

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Components, Formulations, Deliveries, and Combinations of Tumor Vaccines

ACS Nano, Год журнала: 2024, Номер 18(29), С. 18801 - 18833

Опубликована: Июль 9, 2024

Tumor vaccines, an important part of immunotherapy, prevent cancer or kill existing tumor cells by activating restoring the body's own immune system. Currently, various formulations vaccines have been developed, including cell membrane DNA mRNA polypeptide virus-vectored and tumor-in-situ vaccines. There are also multiple delivery systems for such as liposomes, vesicles, viruses, exosomes, emulsions. In addition, to decrease risk escape tolerance that may exist with a single vaccine, combination therapy radiotherapy, chemotherapy, checkpoint inhibitors, cytokines, CAR-T therapy, photoimmunotherapy is effective strategy. Given critical role in here, we look back history discuss antigens, adjuvants, formulations, systems, mechanisms, future directions

Язык: Английский

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Lymphoid organ-targeted nanomaterials for immunomodulation of cancer, inflammation, and beyond

Chemical Society Reviews, Год журнала: 2024, Номер 53(15), С. 7657 - 7680

Опубликована: Янв. 1, 2024

Nanomaterials exhibit significant potential for stimulating immune responses, offering both local and systemic modulation across a variety of diseases. The lymphoid organs, such as the spleen lymph nodes, are home to various cells, including monocytes dendritic which contribute progression prevention/treatment Consequently, many nanomaterial formulations being rationally designed target these organs engage with specific cell types, thereby inducing therapeutic protective effects. In this review, we explore crucial cellular interactions processes involved in regulation highlight innovative nano-based immunomodulatory approaches. We outline essential considerations design an emphasis on their impact biological interactions, targeting capabilities, treatment efficacy. Through selected examples, illustrate strategic therapeutically active nanomaterials subsequent immunomodulation infection resistance, inflammation suppression, self-antigen tolerance, cancer immunotherapy. Additionally, address current challenges, discuss emerging topics, share our outlook future developments field.

Язык: Английский

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Cancer vaccines: platforms and current progress

Molecular Biomedicine, Год журнала: 2025, Номер 6(1)

Опубликована: Янв. 10, 2025

Abstract Cancer vaccines, crucial in the immunotherapeutic landscape, are bifurcated into preventive and therapeutic types, both integral to combating oncogenesis. Preventive cancer like those against HPV HBV, reduce incidence of virus-associated cancers, while vaccines aim activate dendritic cells cytotoxic T lymphocytes for durable anti-tumor immunity. Recent advancements vaccine platforms, such as synthetic peptides, mRNA, DNA, cellular, nano-vaccines, have enhanced antigen presentation immune activation. Despite US Food Drug Administration approval several full potential remains unrealized due challenges selection, tumor-mediated immunosuppression, optimization delivery systems. This review provides a comprehensive analysis aims implications vaccine, innovative discovery neoantigens enhancing specificity, latest strides platforms. It also critically evaluates role adjuvants immunogenicity mitigating immunosuppressive tumor microenvironment. The further examines synergistic combining with other therapies, chemotherapy, radiotherapy, checkpoint inhibitors, improve outcomes. Overcoming barriers effective identification, microenvironments, adverse effects is critical advancing development. By addressing these challenges, can offer significant improvements patient outcomes broaden scope personalized immunotherapy.

Язык: Английский

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Mitigating Doxorubicin‐Induced Cardiotoxicity and Enhancing Anti‐Tumor Efficacy with a Metformin‐Integrated Self‐Assembled Nanomedicine

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Март 7, 2025

Doxorubicin (Dox) is a potent chemotherapeutic agent commonly used in cancer treatment. However, cardiotoxicity severely limited its clinical application. To address this challenge, novel self-assembled nanomedicine platform, PMDDH, developed for the co-delivery of Dox and metformin, an antidiabetic drug with cardioprotective anti-tumor properties. PMDDH integrates metformin into polyethyleneimine-based bioactive excipient (PMet), intercalated double-stranded DNA hyaluronic acid (HA) coating to enhance tumor targeting. The significantly improves pharmacokinetics tumor-targeting capabilities Dox, while enhances drug's activity by downregulating programmed cell death ligand 1 (PD-L1) activating AMP-activated protein kinase (AMPK) signaling pathway. Additionally, component stimulates cyclic GMP-AMP synthase-stimulator interferon genes (cGAS-STING) pathway, which synergizes Dox-induced immunogenic (ICD) promote robust immune response. markedly reduces preserving mitochondrial function, reducing reactive oxygen species (ROS) production, inducing protective autophagy cardiomyocytes. These findings position as promising dual-function that efficacy minimizing systemic toxicity, offering safer more effective alternative therapy.

Язык: Английский

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Navigating the intricate in-vivo journey of lipid nanoparticles tailored for the targeted delivery of RNA therapeutics: a quality-by-design approach

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Ноя. 14, 2024

RNA therapeutics, such as mRNA, siRNA, and CRISPR–Cas9, present exciting avenues for treating diverse diseases. However, their potential is commonly hindered by vulnerability to degradation poor cellular uptake, requiring effective delivery systems. Lipid nanoparticles (LNPs) have emerged a leading choice in vivo delivery, offering protection against degradation, enhanced facilitation of endosomal escape. LNPs encounter numerous challenges targeted vivo, demanding advanced particle engineering, surface functionalization with targeting ligands, profound comprehension the biological milieu which they function. This review explores structural physicochemical characteristics LNPs, in-vivo fate, customization therapeutics. We highlight quality-by-design (QbD) approach beyond liver, focusing on biodistribution, immunogenicity, toxicity. In addition, we explored current strategies associated ensuring repeated-dose efficacy, safety, tissue-specific gene delivery. Furthermore, provide insights into clinical applications various classes diseases finally prospects

Язык: Английский

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Personalized Nanovaccines Enhance Lymph Node Accumulation and Reprogram the Tumor Microenvironment for Improved Photodynamic Immunotherapy

Nano Letters, Год журнала: 2024, Номер 24(24), С. 7432 - 7442

Опубликована: Май 20, 2024

Tumor immunotherapy has emerged as an efficacious therapeutic approach that mobilizes the patient's immune system to achieve durable tumor suppression. Here, we design a photodynamic therapy-motivated nanovaccine (Dex-HDL/ALA-Fe

Язык: Английский

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Engineered Cancer Nanovaccines: A New Frontier in Cancer Therapy

Nano-Micro Letters, Год журнала: 2024, Номер 17(1)

Опубликована: Сен. 30, 2024

Abstract Vaccinations are essential for preventing and treating disease, especially cancer nanovaccines, which have gained considerable interest recently their strong anti-tumor immune capabilities. Vaccines can prompt the system to generate antibodies activate various cells, leading a response against tumor tissues reducing negative effects recurrence risks of traditional chemotherapy surgery. To enhance flexibility targeting vaccines, nanovaccines utilize nanotechnology encapsulate or carry antigens at nanoscale level, enabling more controlled precise drug delivery responses. Cancer function by encapsulating tumor-specific tumor-associated within nanomaterials. The small size these nanomaterials allows T dendritic thereby eliciting potent response. In this paper, we focus on classification carriers roles different target clinically tested discussing strategies effectively inducing cytotoxic lymphocytes responses optimizing antigen presentation, while also looking ahead translational challenges moving from animal experiments clinical trials.

Язык: Английский

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Identification of PLAC1 as a prognostic biomarker and molecular target in clear cell renal cell carcinoma

Cellular Signalling, Год журнала: 2025, Номер 127, С. 111606 - 111606

Опубликована: Янв. 13, 2025

Clear cell renal carcinoma (ccRCC) is a common clinical tumor of the urinary system. The lack effective diagnostic and treatment options poses serious challenge to treatment. Therefore, identifying molecular targets has become one potential means treat this disease. Firstly, analysis TCGA database found that PLAC1 was abnormally highly expressed in ccRCC negatively correlated with patient prognosis. Western blotting immunofluorescence experiments further verified patients, knockdown inhibited development vitro. Last, high-throughput virtual screening technology (HTVS) performed identify two inhibitors ，AmB Cana, which were able reduce expression progression ccRCC. In conclusion, current investigation indicated could serve as prognostic biomarker, AmB Cana inhibit by reducing PLAC1, making it therapeutic option for

Язык: Английский

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Topology‐Oriented Lymph Node Drainage of Dendritic Polymer‐TLR Agonist Conjugates to Enhance Vaccine Immunogenicity

Advanced Materials, Год журнала: 2025, Номер unknown

Опубликована: Фев. 17, 2025

Strategically targeting lymph nodes (LNs) to orchestrate the initiation and regulation of adaptive immune responses is one most pressing challenges in context vaccination. Herein, a series polymer-TLR agonist conjugates (PTACs) developed investigate impact dendritic-topological characteristics on their LN activity vivo, molecular weight (MW) pharmacokinetics support homing. Notably, dendritic 6-arm PTAC with MW 60 kDa (6A-PTAC-60k) rapidly delivered cargo draining LNs after administration peripheral tissues. Specifically, this topologic structure ameliorated behavior within lymphatic vessels LNs, including an elevated amount TLR7/8 improved distribution pattern among barrier cells cells, increased permeability, prolonged retention. Furthermore, 6A-PTAC-60k formulation induced broad antibody T cell responses, enhancing vaccine immunogenicity suppressing tumor growth. The results revealed that both topology polymers are crucial factors for immunoadjuvant functional which, turn, enhanced formulation. This study may provide chemical structural basis optimizing design delivery systems.

Язык: Английский

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