Modulation of FGF pathway signaling and vascular differentiation using designed oligomeric assemblies

Cell, Journal Year: 2024, Volume and Issue: 187(14), P. 3726 - 3740.e43

Published: June 10, 2024

Language: Английский

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What influences the activity of Degrader−Antibody conjugates (DACs)

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 268, P. 116216 - 116216

Published: Feb. 3, 2024

Language: Английский

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Cell-Penetrating Peptide Like Anti-Programmed Cell Death-Ligand 1 Peptide Conjugate-Based Self-Assembled Nanoparticles for Immunogenic Photodynamic Therapy

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 6, 2025

The tumor-specific efficacy of the most current anticancer therapeutic agents, including antibody-drug conjugates (ADCs), oligonucleotides, and photosensitizers, is constrained by limitations such as poor cell penetration low drug delivery. In this study, we addressed these challenges developing, a positively charged, amphiphilic Chlorin e6 (Ce6)-conjugated, cell-penetrating anti-PD-L1 peptide nanomedicine (CPPD1) with enhanced tissue permeability. CPPD1 molecule, bioconjugate hydrophobic photosensitizer strongly charged programmed death-ligand 1 (PD-L1) binding (CPP), capable self-assembling into nanoparticles an average size 199 nm in aqueous solution without need for any carriers. These carrier-free possess ability to penetrate membrane cancer cells target tumors expressing PD-L1 on their surface. Notably, effectively blocked death-1 (PD-1)/PD-L1 interactions reduced expression via lysosomal degradation. They also demonstrated responsiveness photodynamic therapy (PDT) 635 laser, leading generation ROS, induction various immunogenic deaths (ICD). Highly penetrating could immunogenically modulate microenvironment CT26 were effective treating abscopal metastatic tumors, addressing major traditional PDT.

Language: Английский

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Dual site reactivity of indole-3-Schiff bases with S/Se/Cl substituted ketenes for stereoselective C-4 substituted indole-β-lactams, biological evaluations, magic chloro effect and molecular docking studies

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 147, P. 107337 - 107337

Published: April 14, 2024

Language: Английский

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A humanized trivalent Nectin-4-targeting nanobody drug conjugate displays potent antitumor activity in gastric cancer

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 16, 2024

Gastric cancer represents a highly lethal malignancy with an elevated mortality rate among patients, coupled suboptimal postoperative survival prognosis. Nectin-4, overexpressed oncological target for various cancers, has been exploited to create antibody-drug conjugates (ADCs) treat solid tumors. However, there is limited research on Nectin-4 ADCs specifically gastric cancer, and conventional immunoglobulin G (IgG)-based frequently encounter binding site barriers. Based the excellent tumor penetration capabilities inherent in nanobodies (Nbs), we developed Nectin-4-targeting Nb drug (NDCs) treatment of cancer.

Language: Английский

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Unlocking the potential of bispecific ADCs for targeted cancer therapy

Frontiers of Medicine, Journal Year: 2024, Volume and Issue: 18(4), P. 597 - 621

Published: July 23, 2024

Language: Английский

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Opportunities and Challenges in Antibody–Drug Conjugates for Cancer Therapy: A New Era for Cancer Treatment

Cancers, Journal Year: 2025, Volume and Issue: 17(6), P. 958 - 958

Published: March 12, 2025

The antibody, linker, and payload moieties all play a significant role in giving the ADC its unique therapeutic potential. antibody subclass employed ADCs is determined based on relative individual receptor affinities pharmacokinetics. Meanwhile, linker used an can either be cleavable or non-cleavable. therapy comprises antibody-dependent mechanisms addition to direct cytotoxic effects of payload. These include cellular cytotoxicity, complement-dependent phagocytosis, as well “bystander effect”, which refers diffusion portion molecules out target cell, exerting effect adjacent cells. Target antigens are expected expressed membranes cancer cells facing external matrix, although new approaches utilize regarding tumor-associated cells, tumor microenvironment, vasculature. not only determine efficacy these agents but also impact off-targets related adverse effects. majority ADC-related toxicities associated with off-targets. proposed resistance disrupted intracellular drug trafficking, dysfunctional lysosomal processing, efflux molecule via ATP-binding cassette (ABC) transporters. latter mechanism especially prominent for multi-drug-resistant tumors. An important limitation penetration conjugate into microenvironment their delivery Cancerous tissues’ vascular profile steric “binding site barrier” formed around peripheral vessels tumors stand potential challenges solid As research efforts focus reducing toxicities, overcoming resistance, improving pharmacokinetics, options continue diversify, including standalone combination therapies.

Language: Английский

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A Supramolecular, Triple Negative Breast Cancer‐Targeting Avidin‐Photosensitizer

Macromolecular Bioscience, Journal Year: 2025, Volume and Issue: unknown

Published: March 25, 2025

The potential of photodynamic therapy (PDT) in combination with chemotherapy to improve treatment outcomes for triple-negative breast cancer (TNBC), which no targeted is available, the subject considerable investigation. In PDT, photosensitizers (PSs) are frequently administered directly but do not selectively target cells. To address delivery a PS TNBC and enhance cellular uptake, Ru-NH2-modified avidin bioconjugate (RuAvi) via Tyr-specific modification using Mannich reaction prepared. RuAvi further assembled cinnamoyl peptide-F(D)LF(D)LFK-NH2 (FK), binds formyl peptide receptor 1, overexpressed TNBC. Notably, modified Avi still possesses ability efficiently bind biotin assembly up four copies FK peptides. resultant FK4-RuAvi exhibited an IC50 value 0.36 ± 0.08 µM, ≈3.5-fold lower than that (1.25 0.09 µM), upon irradiation MDA-MB-231 also shows efficient uptake tumor spheroids significant toxicity after compared control RuAvi. presented strategy has efficacy PDT meet high demand therapies treat TNBC, such as adjuvant surgery.

Language: Английский

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Bioactive Polymeric Scaffolds: Multivalent Functionalization by Thermal Azide–Alkyne Cycloaddition with Alkynyl Dicarbamates

Biomacromolecules, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

Multivalency enables interactions with higher affinities and specificities than monovalent interactions. The strategy exploited by nature to modulate biorecognition has inspired the design of multivalent conjugates therapeutic properties. However, chemical functionalization often requires coupling agents, additives, or metal catalysts that complicate isolation purification. Herein, azide–alkyne cycloaddition (AAC) alkynyl dicarbamates (Alk-R) is presented as a flexible, reliable, atom-economical, user-friendly for polymeric scaffolds. Alk-R functionalized biologically relevant ligands have been prepared used AAC azide-bearing dendrimers block copolymers. resulting polymers double multivalency reveal platform development bioinspired functional systems promising applications in drug delivery: copolymer micelles multifunctional nanocarriers synergistically integrated probes-ligands-drugs. extension this other scaffolds expected open up wide range diagnostic opportunities.

Language: Английский

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The Emerging Role of Cell Membrane-coated Nanomaterials in Cancer Therapy

Current Pharmaceutical Design, Journal Year: 2024, Volume and Issue: 30(10), P. 727 - 741

Published: March 1, 2024

Abstract: This review investigates the revolutionary application of cell membrane-coated nanoparticles (CMNPs) as a promising avenue for cancer therapy within embryonic landscape nanotechnology. Nanoparticles, pivotal in treatment, are systematically examined their diverse physicochemical structures, categorized organic (lipid-based, protein-based, and polymer-assisted) inorganic (carbon-based metal) varieties. A significant focus is placed on CMNPs, which serve an innovative drug delivery vehicle, overcoming limitations associated with conventional nanoparticle therapies. manuscript accurately explores advantages challenges various membranes, including those derived from cells, red blood platelets, stem white cells. Importance roles enhancing precision, immune system circumvention, targeted recognition. Detailed insights into crafting CMNPs provided, elucidating membrane extraction fusion techniques, such sonication, extrusion, co-extrusion, microfluidic electroporation. Maintaining integrity during benefits coating techniques augmenting biocompatibility underscored. comprehensive resource consolidates latest advancements delivery, positioning itself at forefront nanotechnology biomedicine research. Encapsulating methodologies like electrospray, chemical conjugation, this showcases expanding toolbox available to researchers dynamic field. Focusing unique characteristics multifaceted applications biomedical research, particularly tumour therapy. It provides indepth analysis stability, evasion capabilities, increased payload capacity, retained biological functionality. The outlines current future prospects chemotherapy, photothermal photodynamic therapy, immunotherapy, gene therapeutic methods. concludes by highlighting transformative potential reshaping treatment.

Language: Английский

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