Microtubule-Targeting NAP Peptide-Ru(II)-polypyridyl Conjugate As a Bimodal Therapeutic Agent for Triple Negative Breast Carcinoma DOI

Atin Chatterjee,

Sandip Sarkar, Sangheeta Bhattacharjee

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 26, 2024

Triple-negative breast cancer (TNBC) poses significant treatment challenges due to its high metastasis, heterogeneity, and poor biomarker expression. The N-terminus of an octapeptide NAPVSIPQ (NAP) was covalently coupled a carboxylic acid derivative Ru(2,2′-bipy)32+ (Rubpy) synthesize N-stapled short peptide-Rubpy conjugate (Ru-NAP). This photosensitizer (PS) utilized treat TNBC through microtubule (MT) targeted chemotherapy photodynamic therapy (PDT). Ru-NAP formed more elaborate molecular aggregates with fibrillar morphology as compared NAP. A much higher binding affinity over NAP toward β-tubulin (KRu-NAP: (6.8 ± 0.55) × 106 M–1; KNAP: (8.2 1.1) 104 M–1) observed stronger electrostatic interactions between the MT average linear charge density ∼85 e/nm cationic Rubpy part Ru-NAP. also supported by docking, simulation, appropriate imaging studies. promoted serum stability, specific E-site βIII-tubulin followed disruption network, effective singlet oxygen generation in cells (MDA-MB-231), causing cell cycle arrest G2/M phase triggering apoptosis. Remarkably, MDA-MB-231 were sensitive noncancerous human embryonic kidney (HEK293 cells) when exposed light (LightIC50Ru-NAP[HEK293]: 17.2 2.5 μM, LightIC50Ru-NAP[MDA-MB-231]: 32.5 7.8 nM, DarkIC50Ru-NAP[HEK293]: > 80 DarkIC50Ru-NAP[MDA-MB-231]: 2.9 0.5 μM). effectively inhibited tumor growth xenograft models nude mice. Our findings provide strong evidence that has potential therapeutic role treatment.

Language: Английский

Synthesis and Investigation of Peptide–Drug Conjugates Comprising Camptothecin and a Human Protein‐Derived Cell‐Penetrating Peptide DOI Creative Commons
Isabella R. Palombi, Andrew M. White, Yasuko Koda

et al.

Chemical Biology & Drug Design, Journal Year: 2025, Volume and Issue: 105(1)

Published: Jan. 1, 2025

ABSTRACT Drug targeting strategies, such as peptide–drug conjugates (PDCs), have arisen to combat the issue of off‐target toxicity that is commonly associated with chemotherapeutic small molecule drugs. Here we investigated ability PDCs comprising a human protein‐derived cell‐penetrating peptide—platelet factor 4‐derived internalization peptide (PDIP)—as strategy improve selectivity camptothecin (CPT), topoisomerase I inhibitor suffers from toxicity. The intranuclear target CPT allowed exploration PDC design features required for optimal potency. A suite various structural characteristics, including alternative conjugation strategies (such azide–alkyne cycloaddition and disulfide conjugation) linker types (non‐cleavable or cleavable), were synthesized their anticancer activity. Membrane permeability cytotoxicity studies revealed intact PDIP‐CPT can cross membranes, disulfide‐ protease‐cleavable linkers liberated free killed melanoma cells nanomolar However, PDIP carrier compared noncancerous epidermal was not maintained PDCs. This study emphasizes distinct role peptide, linker, drug activity highlights need carefully match components when assembling targeted therapies.

Language: Английский

Citations

1
Advance in peptide-based drug development: delivery platforms, therapeutics and vaccines DOI Creative Commons
Wen‐Jing Xiao, Wenjie Jiang, Zheng Chen

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 5, 2025

The successful approval of peptide-based drugs can be attributed to a collaborative effort across multiple disciplines. integration novel drug design and synthesis techniques, display library technology, delivery systems, bioengineering advancements, artificial intelligence have significantly expedited the development groundbreaking drugs, effectively addressing obstacles associated with their character, such as rapid clearance degradation, necessitating subcutaneous injection leading increasing patient discomfort, ultimately advancing translational research efforts. Peptides are presently employed in management diagnosis diverse array medical conditions, diabetes mellitus, weight loss, oncology, rare diseases, additionally garnering interest facilitating targeted platforms advancement vaccines. This paper provides an overview present market clinical trial progress therapeutics, platforms, It examines key areas through literature analysis emphasizes structural modification principles well recent advancements screening, design, technologies. accelerated including peptide-drug complexes, new vaccines, innovative diagnostic reagents, has potential promote era precise customization disease therapeutic schedule.

Language: Английский

Citations

1
Tuneable redox-responsive albumin-hitchhiking drug delivery to tumours for cancer treatment DOI Creative Commons

Shiwei Fu,

Ajay Zheng,

Lukun Wang

et al.

Journal of Materials Chemistry B, Journal Year: 2024, Volume and Issue: 12(27), P. 6563 - 6569

Published: Jan. 1, 2024

A novel drug delivery system hitchhiking albumin as a carrier with tuneable redox-responsive release.

Language: Английский

Citations

5
Cyclic peptides: a powerful instrument for advancing biomedical nanotechnologies and drug development DOI Creative Commons

Paul Cristian Martian,

Mihaela Tertiş, Denisa Leonte

et al.

Journal of Pharmaceutical and Biomedical Analysis, Journal Year: 2024, Volume and Issue: 252, P. 116488 - 116488

Published: Sept. 27, 2024

Language: Английский

Citations

5
Applications of cell penetrating peptide-based drug delivery system in immunotherapy DOI Creative Commons
Jingjing Du, Ruyan Zhang, Shuqi Jiang

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 22, 2025

Cell penetrating peptides (CPPs) are usually positive charged and have good cell membrane permeability. Meanwhile, CPPs facile to synthesize, can be functionalized satisfy different demands, such as cyclization, incorporating unnatural amino acids, lipid conjugation. These properties made them efficient drug-delivery tools deliver therapeutic molecules cells tissues in a nontoxic manner, including small molecules, DNA, siRNA, proteins other various nanoparticles. However, the poor serum stability low tumor targeting ability also hindered their broad application. Besides, inappropriate chemical modification lead disruption nonspecific toxicity. In this paper, we first reviewed recent advances CPP applications for cancer therapy via covalent or non-covalent manners. We carefully analyzed advantages disadvantages of each modifications drug delivery. Then, concluded progress clinical trials diseases. Finally, discussed challenges opportunities met translate into applications. This review presented new insight delivery, which could provide advice on design clinically effective systemic delivery systems using CPPs.

Language: Английский

Citations

0
Modern Approaches to Protein Constructions: A Comprehensive Review of Computational Tools and Databases for De Novo Protein Design and Engineering DOI Creative Commons

Md. Mojnu Mia,

Habiba Sultana, Md. Al Amin

et al.

Engineering Reports, Journal Year: 2025, Volume and Issue: 7(2)

Published: Feb. 1, 2025

ABSTRACT The field of protein engineering has witnessed transformative advancements, with computational tools and databases driving novel innovations in de novo design. This review consolidates critiques a comprehensive range modern resources, offering unique focus on their applications across diverse domains, including stability prediction, posttranslational modification analysis, mutation effect evaluation. Key contributions include detailed examination integrating machine learning artificial intelligence to enhance predictive accuracy streamline workflows. By highlighting underexplored methodologies, such as advanced protein–ligand interaction predictors neural network–based assessment models, this study establishes itself reference for researchers aiming develop tailored proteins therapeutic, industrial, biomedical applications.

Language: Английский

Citations

0
Innovative design concepts in tumor-targeting peptide-drug conjugates: Insights into emerging applications DOI Creative Commons
Ruirong Tan,

Zhenya Yang,

Xie Jun

et al.

Chinese Medical Journal, Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Abstract Peptide-drug conjugates (PDCs) have emerged as a promising strategy in cancer therapy, offering improved therapeutic efficacy and reduced toxicity. Compared to antibody-drug (ADCs) small molecule-drug (SMDCs), PDCs possess distinct advantages, such lower immunogenicity, tumor penetration, simpler synthesis. This review discusses the latest advancements PDC design, including novel peptide targeting mechanisms, linker selection, formulation improvements for increased stability. Additionally, it explores expanding clinical applications of examines their limitations. The aim this is provide comprehensive overview current progress outline future directions role treatment.

Language: Английский

Citations

0
Selecting Peptides for Targeted Delivery of Drugs Inside Cancer Cells DOI

Kalimuthu Kalishwaralal,

Abhishek Singh,

Sachin Sharma

et al.

International Journal of Peptide Research and Therapeutics, Journal Year: 2025, Volume and Issue: 31(3)

Published: March 17, 2025

Language: Английский

Citations

0
Precision peptide disruptors: The next generation of targeted therapeutics in oncology DOI Creative Commons

Bria O'Gorman,

Sean F. Cooke, Connor M. Blair

et al.

Cellular Signalling, Journal Year: 2025, Volume and Issue: unknown, P. 111783 - 111783

Published: April 1, 2025

Language: Английский

Citations

0
M01 tool: an automated, comprehensive computational tool for generating small molecule-peptide hybrids and docking them into curated protein structures DOI Creative Commons
Mahsa Sheikholeslami, Mohammad Nazari, Afshin Fassihi

et al.

BMC Bioinformatics, Journal Year: 2025, Volume and Issue: 26(1)

Published: April 14, 2025

Language: Английский

Citations

0