Peptide–Drug Conjugates as Next-Generation Therapeutics: Exploring the Potential and Clinical Progress DOI Creative Commons
Krishna Jadhav, Ashwin Abhang, Eknath Kole

et al.

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

Transcytosable Peptide-Paclitaxel Prodrug Nanoparticle for Targeted Treatment of Triple-Negative Breast Cancer DOI Open Access

Longkun Wang,

Chunqian Zhao,

Lu Lu

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4646 - 4646

Published: Feb. 28, 2023

Triple-negative breast cancer (TNBC) is an extremely aggressive subtype associated with a poor prognosis. At present, the treatment for TNBC mainly relies on surgery and traditional chemotherapy. As key component in standard of TNBC, paclitaxel (PTX) effectively inhibits growth proliferation tumor cells. However, application PTX clinical limited due to its inherent hydrophobicity, weak penetrability, nonspecific accumulation, side effects. To counter these problems, we constructed novel conjugate based peptide-drug conjugates (PDCs) strategy. In this conjugate, fused peptide TAR consisting tumor-targeting peptide, A7R, cell-penetrating TAT, used modify PTX. After modification, named PTX-SM-TAR, which expected improve specificity penetrability at site. Depending hydrophilic hydrophobic PTX, PTX-SM-TAR can self-assemble into nanoparticles water solubility terms linkage, acid- esterase-sensitive ester bond was as linking bond, NPs could remain stable physiological environment, whereas be broken released A cell uptake assay showed that were receptor-targeting mediate endocytosis by binding NRP-1. The vascular barrier, transcellular migration, spheroids experiments exhibit great transvascular transport penetration ability. vivo experiments, higher antitumor effects than result, may overcome shortcomings present new transcytosable targeted delivery system treatment.

Language: Английский

Citations

18
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

7
Design and synthesis of TH19P01-Camptothecin based hybrid peptides inducing effective anticancer responses on sortilin positive cancer cells DOI
Yajie Li,

Chang-Bo Fang,

Shu‐shu Wang

et al.

Bioorganic & Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 111, P. 117869 - 117869

Published: Aug. 3, 2024

Language: Английский

Citations

6
Lenvatinib resistance mechanism and potential ways to conquer DOI Creative Commons

Wentao Bo,

Yan Chen

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: April 20, 2023

Graphical Abstract In this review, we summerized the absorption, distribution, metabolism, excretion of lenvatinib in clinic. The lastest mechanism and potential approches to overcome resistance caused by were supplied.

Language: Английский

Citations

15
Development of a 18F-Labeled Bicyclic Peptide Targeting EphA2 for Molecular Imaging of PSMA-Negative Prostate Cancer DOI

Qianqian Gan,

Kai Cui, Qi Cao

et al.

Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 66(21), P. 14623 - 14632

Published: Nov. 1, 2023

Although PSMA PET/CT imaging has great potential for noninvasively detecting prostate cancer (PCa), limitations exist patients with low expression, caused by androgen deprivation treatment or neuroendocrine differentiation. Analysis of The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) data found that erythropoietin-producing hepatocellular receptor A2 (EphA2), a overexpressed in most PCa could be target PSMA-negative PCa. A fluorescent ligand ETF and radiolabeled [18F]AlF-ETN derived from EphA2-targeting bicyclic peptide were synthesized investigated. selectively stain visualize the EphA2-positive but PC3 cells, complementary to PSMA-targeting probe. biodistribution experiments demonstrated specifically accumulated tumors high contrast (tumor-to-muscle ratio: 21.29 ± 6.55). In conclusion, we have using EphA2 detect developed image expressing contrast.

Language: Английский

Citations

11
Development of Novel Peptide-Based Radiotracers for Detecting FGL1 Expression in Tumors DOI

Yue Xu,

Jinyuan Zhang,

Donghui Pan

et al.

Molecular Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 2, 2025

A novel immune checkpoint, FGL1, is a potentially viable target for tumor immunotherapy. The development of FGL1-targeted PET probes could provide significant insights into the system's status and evaluation treatment efficacy. ClusPro 2.0 server was used to analyze interaction between FGL1 LAG3, candidate peptides were identified by using Rosetta peptide derivate protocol. Three targeting named FGLP21, FGLP22, FGLP23, with simulated affinity −9.56, −8.55, −8.71 kcal/mol, respectively, identified. readily conjugated p-NCS-benzyl-NODA-GA, resulting compounds successfully labeled 68Ga in approximately 70% yields radiochemical purity greater than 95%. In vitro competitive cell-binding assay demonstrated that all bound IC50 ranging from 100 nM 160 nM. Among probes, imaging revealed 68Ga-NODA-FGLP21 exhibited best performance mice bearing positive Huh7 tumor. At 60 min p.i., uptake significantly higher those 68Ga-NODA-FGLP22 68Ga-NODA-FGLP23, respectively (2.51 ± 0.11% ID/g vs 1.00 0.16% 1.49 0.05% ID/g). Simultaneously, tumor-to-muscle ratios former also latter, (19.40 2.30 9.65 0.62 12.45 0.72). presence unlabeled xenograft decreased 0.81 0.09% at which similar observed negative U87 MG (0.46 0.03% results consistent immunohistochemical analysis ex vivo autoradiography. No radioactivity accumulated normal organs, except kidneys. summary, preclinical study confirmed tracer has potential specifically detect expression tumors good contrast background.

Language: Английский

Citations

0
Discovery of novel HER2 targeting peptide-camptothecin conjugates with effective suppression for selective cancer treatment DOI
Hanyu Wu, Yunxiao Liu, Jiaqi Zhou

et al.

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 147, P. 107371 - 107371

Published: April 15, 2024

Language: Английский

Citations

3
Peptides as innovative strategies to combat drug resistance in cancer therapy DOI Creative Commons

Henry Lamb,

Aurélie H. Benfield, Sónia Troeira Henriques

et al.

Drug Discovery Today, Journal Year: 2024, Volume and Issue: 29(12), P. 104206 - 104206

Published: Oct. 10, 2024

Drug resistance is the leading cause of treatment failure in patients with cancer. Thus, innovative therapeutic strategies are required to overcome this critical challenge and improve patient outcomes. In review, we examine potential peptide-based therapies combat drug We highlight unique mechanisms that can be explored by using peptides, including their ability selectively target tumours, facilitate delivery into cancer cells, inhibit key intracellular proteins drive progression resistance. Peptides offer a promising approach overcoming both intrinsic adaptative against chemotherapy, targeted therapies, biologics.

Language: Английский

Citations

3
Multiomics analysis reveals the involvement of NET1 in tumour immune regulation and malignant progression DOI Creative Commons
Jian Pang, Xiaoyan Huang, Ya Gao

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 2, 2025

Language: Английский

Citations

0
The validation and clinical bioanalysis of the Bicycle® Toxin Conjugate zelenectide pevedotin in human plasma DOI
Joseph Tweed, Fern Adams-Dam,

Justin Bader

et al.

Bioanalysis, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 9

Published: Jan. 19, 2025

Background The Bicycle® toxin conjugate (BTC) zelenectide pevedotin, formerly known as BT8009, is a novel bicyclic peptide targeting the Nectin-4 tumor antigen conjugated to cytotoxin monomethyl auristatin E (MMAE) via valine-citrulline cleavable linker. Zelenectide pevedotin currently being investigated in Phase 1/2 (Duravelo-1, NCT04561362) clinical trial determine safety and efficacy patients with tumors associated expression. A simple regulated bioanalytical assay was developed quantify intact patient plasma samples.

Language: Английский

Citations

0