TKD peptide as a ligand targeting drug delivery systems to memHsp70-positive breast cancer

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Breast cancer poses a significant threat to women's health.
• Active targeting drug delivery systems offer promise for cancer therapy but face challenges in targeting efficiency.
• Membrane heat-shock protein 70 (memHsp70) is a potential target for cancer therapy.

Purpose of the Study:

• To investigate the potential of a novel 14-mer peptide (TKD) as a tumor-targeting ligand for polymeric micelles.
• To evaluate the efficacy of TKD-modified micelles for targeted delivery of doxorubicin (DOX) to breast cancer cells.
• To explore the receptor-mediated targeting mechanism of TKD in vitro and in vivo.

Main Methods:

• Synthesis and characterization of TKD-PEG-PLGA polymer using NMR.
• Preparation and drug release studies of TKD-modified doxorubicin-loaded micelles (TKD-D-M).
• In vitro cellular uptake studies using MCF-7 (memHsp70-positive) and MCF-10A (normal) cells.
• In vivo tumor targeting studies in MCF-7 bearing mice.
• Cell proliferation assays (CCK-8) to assess anti-cancer effects.

Main Results:

• Successful synthesis of TKD-PEG-PLGA polymer confirmed by NMR.
• TKD modification did not affect doxorubicin release kinetics.
• TKD-modified micelles showed significantly higher cellular uptake in memHsp70-positive MCF-7 cells compared to normal cells.
• Uptake was inhibited by excessive TKD pretreatment, confirming receptor-mediated targeting.
• Enhanced accumulation of TKD-D-M in tumors and increased anti-proliferation effects against MCF-7 cells were observed in vivo.

Conclusions:

• The TKD peptide is a novel and effective ligand for targeting memHsp70-positive breast cancer.
• TKD-modified polymeric micelles demonstrate potential for targeted drug delivery and enhanced anti-cancer therapy.
• This strategy offers a promising approach to improve the efficiency of breast cancer treatment.