Helix-Guarded Molecular Clips for Cell-Free DNA Scavenging and Treatment of Systemic Lupus Erythematosus

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 11, 2025

Immune disorders induced by cell-free DNA (cfDNA) account for the incidence and deterioration of systemic lupus erythematosus (SLE). Scavenging cfDNA using cationic polymers represents a promising modality SLE management. However, they bind mainly via electrostatic interaction, which would result in an undesired discharge captured upon competitive replacement negatively charged serum/intracellular components. Inspired natural recognition mechanism biomacromolecules spatial matching, we herein developed library dendrimer-templated, spherical, α-helical, guanidine-rich polypeptides as molecular clips scavenging. Upon optimization polypeptide length density on dendrimer surface, top-performing G3-8 was identified, could tightly confine within cavity between adjacent, rod-like α-helices. As thus, helical but not random-coiled analogue D,L-G3-8 enabled robust scavenging under serum-rich conditions to inhibit TLR9 activation inflammation. In mice, i.v. injected efficiently prevented organ failure inhibited inflammation cfDNA. This study provides enlightened strategy stably scavenge may shift current paradigm

Language: Английский

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DNA origami-based composite nanosandwich for iteratively potentiated chemo-immunotherapy

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: 379, P. 452 - 465

Published: Jan. 17, 2025

Language: Английский

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Trained immunity-inducing vaccines: Harnessing innate memory for vaccine design and delivery

Clinical Immunology, Journal Year: 2024, Volume and Issue: 261, P. 109930 - 109930

Published: Feb. 9, 2024

While the efficacy of many current vaccines is well-established, various factors can diminish their effectiveness, particularly in vulnerable groups. Amidst emerging pandemic threats, enhancing vaccine responses critical. Our review synthesizes insights from immunology and epidemiology, focusing on concept trained immunity (TRIM) non-specific effects (NSEs) that confer heterologous protection. We elucidate mechanisms driving TRIM, emphasizing its regulation through metabolic epigenetic reprogramming innate immune cells. Notably, we explore extended protective scope like BCG COVID-19 against unrelated infections, underscoring role reducing neonatal mortality combating diseases malaria yellow fever. also highlight novel strategies to boost efficacy, incorporating TRIM inducers into formulations enhance both specific responses. This approach promises significant advancements development, aiming improve global public health outcomes, especially for elderly immunocompromised populations.

Language: Английский

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Supramolecular Polymers for Drug Delivery

Chemistry - A European Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Abstract Supramolecular polymers are constructed through highly reversible and directionally specific non‐covalent interactions between monomer units. This unique feature enables supramolecular to undergo controlled structural reconfiguration functional transformation in response external stimuli, imparting them with high environmental responsiveness self‐healing properties. In particular, exhibit several advantages compared conventional polymers, such as inherent degradability, the ease of preparation incorporation units, smart various biological stimuli. These characters make promising candidates for intelligent drug delivery systems complex environments. this review, we comprehensively summarize latest developments representative achievements fields, focusing primarily on design synthesis, properties functionalities, practical applications small molecule delivery, gene therapy, protein delivery. Finally, highlight future research directions, multifunctionality, adaptability, personalized therapy. We focus recent studies that address key challenges field, providing rational polymer design, important properties, functionality, understanding strategies. expected advance new platforms systems, offering innovative solutions treatment diseases.

Language: Английский

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High-Curvature Features on Branched Nanoconstructs Circumvent Protein Corona Interference

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

This paper reports how the local nanoscale curvature on nanoparticle constructs determines protein corona distribution in biological conditions. Using transmission electron microscopy, we found that DNA-gold nanostar nanoconstructs (DNA-AuNS) having positive-curvature tips <5 nm radius showed less dense and uniform layers compared to 50 gold nanospheres (DNA-50NPs). Statistical analysis based type of AuNS revealed layer thickness was lower than neutral negative regions. Since coronas screen ligands nanoparticles, used DNA hybridization evaluate whether ligand functionality preserved after adsorption proteins. DNA-AuNS with hybridized more 5 nanosphere probes (5NPs) DNA-50NPs. Without layer, two classes higher numbers 5NPs, differences due NP shape were minimal. Notably, exhibited percentages regions; this trend independent sequence. Our work demonstrates importance nanoconstruct mitigating preserving at single-particle level.

Language: Английский

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Co-encapsulated Ce6 + CpG and biopeptide-modified liposomes for enhanced transdermal photo-immunotherapy of superficial tumors

Materials Today Bio, Journal Year: 2025, Volume and Issue: unknown, P. 101669 - 101669

Published: March 1, 2025

Cancer immunotherapy encounters challenges of a low treatment response rate due to the tumor immunosuppressive microenvironment and immune-related adverse events caused by off-target agents delivered through systemic administration in clinical practice. Photodynamic therapy (PDT) offers viable approach improve efficacy inducing immunogenic cell death is particularly advantageous superficial treatment. Therefore, leveraging integrated nanomaterials for photo-immunotherapy appears be an ideal strategy therapeutic outcome. In this study, we develop transdermal-enhancing peptide (TD)-modified cationic liposome that simultaneously encapsulated with photosensitizer chlorine 6 (Ce6) immunoadjuvant CpG, denoted as Ce6/CpG@Lip-TD, mediate tumors via skin. The functionalization TD positively charged surface endow liposomes enhanced skin penetration capability. combination Ce6 CpG within synergistically potentiates effect when exposed laser irradiation. both melanoma breast cancer murine models, Ce6/CpG@Lip-TD demonstrated substantial tumor-suppressing properties, along augmented immune against distal tumors. As topical agent, circumvents regulatory associated delivery significantly reduces side effects, holding great promise rapid translation into applications.

Language: Английский

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Recent advances in DNA nanotechnology for cancer detection and therapy: A review

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 142136 - 142136

Published: March 1, 2025

Language: Английский

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Dynamic DNA-Based Nanoadjuvants for TLR9 Clustering and Innate Immune Activation in Dendritic Cells

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: April 9, 2025

The regulation of toll-like receptor (TLR) clustering is a pivotal strategy for enhancing innate immune responses, but the development methods to precisely control assembly remains challenging. Herein, we present dynamic, DNA-based nanoadjuvant that triggers TLR9 potent activation in dendritic cells (DCs) via situ lysosomes. This integrates CpG oligonucleotides (TLR9 ligands) and cytosine-rich DNA sequences (acid-responsive sequences) into polymeric nanoframework cascade hybridization chain reaction. Upon lysosomal internalization, nanoadjuvants form large-sized aggregates through cytosine protonation-induced i-motif formation, process driven by acidic environment. consumes protons, thus reducing acidity attenuating hydrolase activity, leading enhanced intralysosomal retention nanoadjuvants. Moreover, promote ODN contact with membrane, thereby facilitating prolonged ligand-receptor interactions efficient clustering. Consequently, induce DC maturation, secretion cytokines, T-cell proliferation, culminating robust antitumor immunity both vitro vivo. Our approach offers novel manipulate using an environmentally stimulus-responsive system, holding significant promise vaccine adjuvants cancer immunotherapy.

Language: Английский

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Ferritin and Encapsulin Nanoparticles as Effective Vaccine Delivery Systems: Boosting the Immunogenicity of the African Swine Fever Virus C129R Protein

Viruses, Journal Year: 2025, Volume and Issue: 17(4), P. 556 - 556

Published: April 11, 2025

Vaccination remains the most effective strategy for preventing infectious diseases. Subunit vaccines, which consist of antigenic components derived from pathogens, offer significant advantages in terms biosafety, ease preparation, and scalability. However, subunit vaccines often exhibit lower immunogenicity than whole-pathogen do. To address this limitation, coupling antigens with nanoparticles has emerged as a promising enhancing immune responses by mimicking pathogen structures improving antigen presentation. This study evaluated stability ferritin (F-nps) encapsulin (E-nps) their efficient uptake bone-marrow-derived dendritic cells (BMDCs) vitro. In vivo studies demonstrated targeting lymph nodes. The African swine fever virus C129R protein was conjugated to assess its ability enhance antigen-specific responses. murine models, both F-nps E-nps significantly increased antigen, highlighting potential vaccine delivery systems. These findings underscore promise platforms pave way development nanoparticle-based vaccines.

Language: Английский

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Enhancing melanoma therapy with hydrogel microneedles

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: April 17, 2025

Melanoma is highly invasive and resistant to conventional treatments, accounting for nearly 75% of skin cancer-related deaths globally. Traditional therapies, such as chemotherapy immunotherapy, often exhibit limited efficacy are associated with significant side effects due systemic drug exposure. Microneedles (MNs), an emerging delivery system, offer multiple advantages, including safety, painlessness, minimal invasiveness, controlled release. Among these, hydrogel microneedles (HMNs) stand out their extracellular matrix-like structure swelling-induced continuous channels, which enable the direct therapeutic agents into tumor microenvironment (TME). This approach enhances bioavailability while reducing toxicity, establishing HMNs a promising platform melanoma treatment. review highlights recent advancements in therapy, focusing on applications biomarker extraction early diagnosis role supporting multimodal treatment strategies, chemotherapy, phototherapy, targeted combination therapy. Furthermore, current matrix materials fabrication techniques discussed. Finally, limitations critically analyzed, recommendations future research development provided.

Language: Английский

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