In Silico Discovery of Multi-Target Natural Ligands and Efficient siRNA Design for Overcoming Drug Resistance in Breast Cancer via Local Therapy DOI Open Access

Seyed Mohammad Javad Hashemi,

Ali Barzegar, Javad Akhtari

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 11, 2024

Abstract In this study, we designed an efficient siRNA for PKMYT1 gene knockdown, and evaluated the binding affinities of different natural ligands to crucial proteins involved in breast cancer. Designed showed strong affinity minimal off-target effects. Molecular docking studies identified new as antagonists with high aromatase, estrogen receptor alpha, HER2, PARP10, well agonists MT2 STING. The ligand SCHEMBL7562664 was introduced a golden due its among multiple targets lack cytotoxic mutagenic Natural small molecules research, their multi-target characteristics, provided solution overcome problem drug resistance cancer cells. Furthermore, proposed three dimensional scaffold design local therapy offers promising approach increase delivery efficacy these molecules, reduce systemic side effects, improve treatment outcomes. significant favorable pharmacokinetic properties were identified, which paves way further research targeted

Language: Английский

Surface Functionalization of Nanocarriers with Anti-EGFR Ligands for Cancer Active Targeting DOI Creative Commons

Alessandra Spada,

Sandrine Gerber‐Lemaire

Nanomaterials, Journal Year: 2025, Volume and Issue: 15(3), P. 158 - 158

Published: Jan. 21, 2025

Active cancer targeting consists of the selective recognition overexpressed biomarkers on cell surfaces or within tumor microenvironment, enabled by ligands conjugated to drug carriers. Nanoparticle (NP)-based systems are highly relevant for such an approach due their large surface area which is amenable a variety chemical modifications. Over past decades, several studies have debated efficiency passive targeting, highlighting active as more specific and approach. The choice conjugation chemistry attaching nanocarriers critical ensure stable robust system. Among panel biomarkers, epidermal growth factor receptor (EGFR) stands one most frequently receptors in different types. design development with surface-bound anti-EGFR vital targeted therapy, relying facilitated capture EGFR-overexpressing cells enabling receptor-mediated endocytosis improve accumulation microenvironment. In this review, we examine examples recent significant explore various strategies NP functionalization biomolecules small molecular ligands. addition, also describe some common characterization techniques confirm analyze patterns.

Language: Английский

Citations

3
Chitosan-based nanoarchitectures for siRNA delivery in cancer therapy: A review of pre-clinical and clinical importance DOI

Xiaobo Bian,

Xiaopeng Yu, Shiyang Lu

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: unknown, P. 137708 - 137708

Published: Nov. 1, 2024

Language: Английский

Citations

6
Chitosan-based hydrogels in cancer therapy: Drug and gene delivery, stimuli-responsive carriers, phototherapy and immunotherapy DOI

Hailin Zhu,

Haowei Sun, Jingyuan Dai

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 282, P. 137047 - 137047

Published: Nov. 1, 2024

Language: Английский

Citations

5
Advances in siRNA Drug Delivery Strategies for Targeted TNBC Therapy DOI Creative Commons
Md Abdus Subhan, Vladimir P. Torchilin

Bioengineering, Journal Year: 2024, Volume and Issue: 11(8), P. 830 - 830

Published: Aug. 14, 2024

Among breast cancers, triple-negative cancer (TNBC) has been recognized as the most aggressive type with a poor prognosis and low survival rate. Targeted therapy for TNBC is challenging because it lacks estrogen receptor (ER), progesterone (PR), human epidermal growth factor 2 (HER2). Chemotherapy, radiation therapy, surgery are common therapies TNBC. Although prone to chemotherapy, drug resistance recurrence commonly associated treatment failure. Combination approaches using mAbs, ADC, antibody–siRNA conjugates may be effective in Recent advances siRNA-based promising better reduced mortality. This review discusses nanomaterial- nanobiomaterial-based siRNA delivery platforms exploring targeted major genes, proteins, TFs upregulated tumors, which engage molecular pathways prognosis. Bioengineered drugs targeting one or several genes simultaneously can downregulate desired significantly reducing disease progression.

Language: Английский

Citations

4
Targeted cancer treatment using a novel EGFR-specific Fc-fusion peptide based on GE11 peptide DOI Creative Commons

Malihe Hallaji,

Mojgan Allahyari, Ladan Teimoori‐Toolabi

et al.

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

Published: Feb. 11, 2025

Fc-fusion peptides, also known as peptibodies, are a promising new category of targeted therapeutics that offer alternatives to monoclonal antibodies (mAbs) for cancer treatment. This study focuses on an peptide consisting the Fc region IgG1 and epidermal growth factor receptor (EGFR)-targeting peptide, GE11, which was identified using phage display method demonstrated high affinity receptor. The fusion (FcIgG-GE11) successfully expressed in Escherichia coli purified ion-exchange chromatography. Flow cytometry confirmed its specific binding EGFR. Like Cetuximab, FcIgG-GE11 peptibody exhibited effective, dose- time-dependent inhibition EGFR-overexpressing cell lines. Additionally, results showed induced death or cycle arrest certain lines, with varying responses depending type. In-Cell ELISA when comparing effects Cetuximab Tyr 1173 phosphorylation were similar. In addition, relative potency compared assessed MTT by Slope Ratio Analysis. These findings suggest can provide efficient tool both targeting treating cells.

Language: Английский

Citations

0
In Silico Discovery of Multi-Target Small Molecules and Efficient siRNA Design to Overcome Drug Resistance in Breast Cancer via Local Therapy DOI

Seyed Mohammad Javad Hashemi,

Hossein Ghalehnoei, Ali Barzegar

et al.

Journal of Molecular Graphics and Modelling, Journal Year: 2025, Volume and Issue: unknown, P. 109086 - 109086

Published: May 1, 2025

Language: Английский

Citations

0
Synthesis of novel phthalazine-based derivatives with potent cytotoxicity against HCT-116 cells through apoptosis and VEGFR2 inhibition DOI Creative Commons

Donia El Sayed,

Samir M. El Rayes, Hamdy A.M. Soliman

et al.

RSC Advances, Journal Year: 2024, Volume and Issue: 14(19), P. 13027 - 13043

Published: Jan. 1, 2024

A novel phthalazine derivative exhibited potent cytotoxicity against HCT-116 cells as VEGFR2 inhibitor and apoptosis cell death.

Language: Английский

Citations

2
The luminescent Nb2C MXene nanosheet-based whispering gallery mode-enhanced ECL strategy for miRNA-214 detection DOI

Yameng Li,

Peilin Wang,

Huan Wang

et al.

Talanta, Journal Year: 2024, Volume and Issue: 279, P. 126627 - 126627

Published: July 27, 2024

Language: Английский

Citations

0
In Silico Discovery of Multi-Target Natural Ligands and Efficient siRNA Design for Overcoming Drug Resistance in Breast Cancer via Local Therapy DOI Open Access

Seyed Mohammad Javad Hashemi,

Ali Barzegar, Javad Akhtari

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 11, 2024

Abstract In this study, we designed an efficient siRNA for PKMYT1 gene knockdown, and evaluated the binding affinities of different natural ligands to crucial proteins involved in breast cancer. Designed showed strong affinity minimal off-target effects. Molecular docking studies identified new as antagonists with high aromatase, estrogen receptor alpha, HER2, PARP10, well agonists MT2 STING. The ligand SCHEMBL7562664 was introduced a golden due its among multiple targets lack cytotoxic mutagenic Natural small molecules research, their multi-target characteristics, provided solution overcome problem drug resistance cancer cells. Furthermore, proposed three dimensional scaffold design local therapy offers promising approach increase delivery efficacy these molecules, reduce systemic side effects, improve treatment outcomes. significant favorable pharmacokinetic properties were identified, which paves way further research targeted

Language: Английский

Citations

0