Recent Advances in Smart Linkage Strategies for Developing Drug Conjugates for Targeted Delivery

Topics in Current Chemistry, Journal Year: 2025, Volume and Issue: 383(2)

Published: March 13, 2025

Language: Английский

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Current progress and remaining challenges of peptide–drug conjugates (PDCs): next generation of antibody-drug conjugates (ADCs)?

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 22, 2025

Drug conjugates have emerged as a promising alternative delivery system designed to deliver an ultra-toxic payload directly the target cancer cells, maximizing therapeutic efficacy while minimizing toxicity. Among these, antibody-drug (ADCs) garnered significant attention from both academia and industry due their great potential for therapy. However, peptide-drug (PDCs) offer several advantages over ADCs, including more accessible industrial synthesis, versatile functionalization, high tissue penetration, rapid clearance with low immunotoxicity. These factors position PDCs up-and-coming drug candidates future Despite potential, face challenges such poor pharmacokinetic properties bioactivity, which hinder clinical development. How design meet needs is big challenge urgent resolve. In this review, we first carefully analyzed general consideration of successful PDC learning ADCs. Then, summarised basic functions each component construct, comprising peptides, linkers payloads. The peptides in were categorized into three types: tumor targeting cell penetrating peptide self-assembling peptide. We then these delivery, overcoming resistance, controlling release improving reduced non-specific To better understand druggability PDCs, discussed pharmacokinetics also briefly introduced current trials. Lastly, perspectives development oncology PDC. This review aimed provide useful information construction applications.

Language: Английский

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Peptide–Drug Conjugates as Next-Generation Therapeutics: Exploring the Potential and Clinical Progress

Bioengineering, Journal Year: 2025, Volume and Issue: 12(5), P. 481 - 481

Published: April 30, 2025

Peptide–drug conjugates (PDCs) have emerged as a next-generation therapeutic platform, combining the target specificity of peptides with pharmacological potency small-molecule drugs. As an evolution beyond antibody–drug (ADCs), PDCs offer distinct advantages, including enhanced cellular permeability, improved drug selectivity, and versatile design flexibility. This review provides comprehensive analysis fundamental components PDCs, homing peptide selection, linker engineering, payload optimization, alongside strategies to address their inherent challenges, such stability, bioactivity, clinical translation barriers. Therapeutic applications span oncology, infectious diseases, metabolic disorders, emerging areas like COVID-19, several advancing in trials achieving regulatory milestones. Innovations, bicyclic peptides, supramolecular architectures, novel technologies, are explored promising avenues enhance PDC design. Additionally, this examines trajectory emphasizing potential highlighting ongoing that exemplify efficacy. By addressing limitations leveraging advancements, hold immense promise targeted therapeutics capable complex disease states driving progress precision medicine.

Language: Английский

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Revealing the multiple faces of LRG1: gene expression, structure, function, and therapeutic potential

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

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Cytotoxic activity and cell specificity of a novel LHRH peptide drug conjugate, D‐Cys6‐LHRH vedotin, against ovarian cancer cell lines

Chemical Biology & Drug Design, Journal Year: 2024, Volume and Issue: 103(4)

Published: April 1, 2024

Abstract Ovarian cancer is the most deadly female gynaecological malignancy in developed countries and new treatments are urgently needed. The luteinising hormone releasing (LHRH) peptide drug conjugate Zoptarelin doxorubicin one such potential modality that entered clinical trials for treating LHRH receptor‐positive cancers. However, development stopped after disappointing Phase 3 results 2017. We believe lack of efficacy was due to linker instability payload potency. In this work, we replaced its linker‐toxin with vedotin (MC‐VC‐PABC‐MMAE), yielding novel D ‐Cys6‐LHRH vedotin. A GI 50 cell specificity comparison against cancerous non‐cancerous ovarian lines showed significantly superior bioactivity selectivity over (GI 4 vs. 453 nM) other chemotherapeutic drugs used Our suggest can potentially be as a treatment cancer.

Language: Английский

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