Related Experiment Video
Updated: Jun 27, 2025
Using In Vitro Live-cell Imaging to Explore Chemotherapeutics Delivered by Lipid-based Nanoparticles
Published on: November 1, 2017
New Transferrin Receptor-Targeted Peptide-Doxorubicin Conjugates: Synthesis and In Vitro Antitumor Activity
Jiale Yu1, Xiaoxia Mao1, Xue Yang2
1Hebei Province Key Laboratory of Research and Development of Traditional Chinese Medicine, Institute of Chinese Mateia Medica, Chengde Medical University, Chengde 067000, China.
Abstract:
Poor selectivity to tumor cells is a major drawback in the clinical application of the antitumor drug doxorubicin (DOX). Peptide-drug conjugates (PDCs) constructed by modifying antitumor drugs with peptide ligands that have high affinity to certain overexpressed receptors in tumor cells are increasingly assessed for their possibility of tumor-selective drug delivery. However, peptide ligands composed of natural L-configuration amino acids have the defects of easy enzymatic degradation and insufficient biological stability. In this study, two new PDCs (LT7-SS-DOX and DT7-SS-DOX) were designed and synthesized by conjugating a transferrin receptor (TfR) peptide ligand LT7 (HAIYPRH) and its retro-inverso analog DT7 (hrpyiah), respectively, with DOX via a disulfide bond linker. Both conjugates exhibited targeted antiproliferative effects on TfR overexpressed tumor cells and little toxicity to TfR low-expressed normal cells compared with free DOX. Moreover, the DT7-SS-DOX conjugate possessed higher serum stability, more sustained reduction-triggered drug release characteristics, and stronger in vitro antiproliferative activity as compared to LT7-SS-DOX. In conclusion, the coupling of antitumor drugs with the DT7 peptide ligand can be used as a promising strategy for the further development of stable and efficient PDCs with the potential to facilitate TfR-targeted drug delivery.
Insights
New peptide-drug conjugates (PDCs) improve doxorubicin (DOX) tumor selectivity. The D-amino acid based PDC showed enhanced stability and efficacy for targeted cancer therapy.
Area of Science:
- Bioconjugation Chemistry
- Cancer Therapeutics
- Drug Delivery Systems
Background:
- Doxorubicin (DOX) exhibits poor tumor selectivity, limiting its clinical use.
- Peptide-drug conjugates (PDCs) offer potential for tumor-selective delivery via targeting overexpressed receptors.
- Natural L-amino acid peptides face enzymatic degradation and stability issues.
Purpose of the Study:
- To design and synthesize novel PDCs for enhanced tumor targeting and stability.
- To evaluate the efficacy and safety of L- and D-amino acid peptide conjugates with DOX.
Main Methods:
- Conjugation of transferrin receptor (TfR) targeting peptides (L-T7 and D-T7) to DOX via a disulfide linker.
- Assessment of antiproliferative effects on TfR-overexpressed tumor cells and normal cells.
- Evaluation of serum stability and drug release kinetics.
Main Results:
- Both L-T7-SS-DOX and D-T7-SS-DOX showed targeted antiproliferative effects on TfR-overexpressing tumor cells.
- Conjugates exhibited reduced toxicity to TfR low-expressing normal cells compared to free DOX.
- D-T7-SS-DOX demonstrated superior serum stability, sustained release, and in vitro activity over L-T7-SS-DOX.
Conclusions:
- Peptide-drug conjugation with D-T7 offers a promising strategy for stable and efficient PDCs.
- This approach facilitates TfR-targeted drug delivery for improved cancer therapy.
- D-amino acid based PDCs present enhanced characteristics for clinical translation.
More Related Videos
11:58Initial Evaluation of Antibody-conjugates Modified with Viral-derived Peptides for Increasing Cellular Accumulation and Improving Tumor Targeting
Published on: March 8, 2018
09:09Synthesis of Aptamer-PEI-g-PEG Modified Gold Nanoparticles Loaded with Doxorubicin for Targeted Drug Delivery
Published on: June 23, 2020
