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Updated: Feb 27, 2026

Initial Evaluation of Antibody-conjugates Modified with Viral-derived Peptides for Increasing Cellular Accumulation and Improving Tumor Targeting

Initial Evaluation of Antibody-conjugates Modified with Viral-derived Peptides for Increasing Cellular Accumulation and Improving Tumor Targeting

Published on: March 8, 2018

ROS-Activated Peptide-Based Prodrug for Chemoselective Covalent Targeting in Cancer Cells.

Shijin Zhang¹, Qinchuan Wei¹, Jiarong Lv¹

¹National Engineering Research Center of Ophthalmology and Optometry, School of Biomedical Engineering, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China.

Journal of Medicinal Chemistry

|February 26, 2026

Summary

This summary is machine-generated.

We developed IRS1, a targeted covalent drug that self-assembles into nanoparticles. It selectively targets cancer cells, releasing a drug payload to induce cancer cell death with reduced toxicity.

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Area of Science:

Drug Delivery
Nanomedicine
Cancer Therapeutics

Background:

Covalent drugs offer high selectivity but face challenges with off-target reactivity.
Developing targeted therapies is crucial for minimizing systemic toxicity in cancer treatment.

Purpose of the Study:

To design and evaluate IRS1, a novel peptide-based prodrug for targeted cancer inhibition.
To investigate the self-assembly, tumor targeting, and drug release mechanisms of IRS1.

Main Methods:

IRS1 synthesis incorporating an RGD motif, ROS-responsive unit, and chlorambucil warhead.
Characterization of IRS1 self-assembly into nanoparticles and transformation into nanofibrils.
In vitro evaluation of cancer cell death induction and in vivo assessment in uveal melanoma xenograft models.

Main Results:

IRS1 self-assembles into nanoparticles, targeting uveal melanoma cells via integrin mediation.
ROS-triggered transformation of IRS1 nanoparticles to nanofibrils exposes the covalent warhead.
IRS1 induces cancer cell death by disrupting membrane integrity and activating apoptosis, showing potent antitumor efficacy in vivo with reduced toxicity.

Conclusions:

IRS1 represents a promising peptide-reconfiguration strategy for tumor-selective covalent therapeutics.
The developed prodrug demonstrates efficient cancer inhibition through targeted drug delivery and controlled release.