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Multi-Layered PLGA-PEI Nanoparticles Functionalized with TKD Peptide for Targeted Delivery of Pep5 to Breast Tumor
Akhil K Mohan1,2, Minsa M3, T R Santhosh Kumar3
1Nano Drug Delivery Systems (NDDS), Cancer Biology Division, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, 695014, India.
Purpose:
Peptide-based therapy is a promising strategy for cancer treatment because of its low drug resistance. However, the major challenge is their inability to target cancer cells specifically. So, a targeted nano-delivery system that could deliver therapeutic peptides selectively to cancer cells to stimulate their action is highly desirable. This study aims to deliver the antitumor peptide, Pep5, to breast tumor cells selectively using a targeting peptide functionalised multi-layered PLGA-PEI nanoparticles.
Methods:
In this study, Pep5 entrapped PLGA-PEI (Pep5-PPN) dual layered nanoparticles were developed. These nanoparticles were decorated with TKD (Pep5-TPPN) on their surface for site-specific delivery of Pep5 to breast tumor cells. The particles were then characterized using various instrumental analyses. In vitro cytotoxicity of the particles was evaluated in estrogen receptor positive (ER+ve) and triple negative breast cancer (TNBC) cells. An ex vivo tumor spheroid model was used to analyze the antitumor activity of the particles.
Results:
Uniformly round Pep5-TPPN particles were synthesized with an average diameter of 420.8 ± 14.72 nm. The conjugation of PEI over Pep5-PLGA nanoparticles shifted the zeta potential from -11.6 ± 2.16 mV to +20.01 ± 2.97 mV. In vitro cytotoxicity analysis proved that TKD conjugation to nanoparticles enhanced the antitumor activity of Pep5 in tested breast cancer cells. Pep5-TPPN induced cytoskeletal damage and apoptosis in the tested cells, which showed that the mechanism of action of Pep5 is conserved but potentiated. Active targeting of Pep5 suppressed the tumor growth in ex vivo spheroid models.
Conclusion:
A multi-layered nanoparticle functionalized with dual peptide was fabricated for active tumor targeting, which stimulated Pep5 activity to reduce the tumor growth in vitro and ex vivo.
Insights
Targeted nanoparticles deliver the antitumor peptide Pep5 to breast cancer cells, enhancing its effectiveness and reducing tumor growth. This peptide-based therapy overcomes drug resistance for improved cancer treatment.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Peptide-based therapies offer low drug resistance for cancer treatment.
- A key challenge is the specific targeting of cancer cells.
- Targeted nano-delivery systems are needed to deliver therapeutic peptides selectively.
Purpose of the Study:
- To develop a targeted nano-delivery system for the antitumor peptide Pep5.
- To selectively deliver Pep5 to breast tumor cells using functionalized nanoparticles.
- To enhance the efficacy of Pep5 in cancer treatment.
Main Methods:
- Developed dual-layered PLGA-PEI nanoparticles encapsulating Pep5 (Pep5-PPN).
- Functionalized nanoparticles with a targeting peptide (TKD) for site-specific delivery (Pep5-TPPN).
- Characterized nanoparticles and evaluated in vitro cytotoxicity and ex vivo antitumor activity.
Main Results:
- Synthesized uniformly round Pep5-TPPN nanoparticles (420.8 ± 14.72 nm).
- TKD conjugation enhanced Pep5's antitumor activity and induced cytoskeletal damage and apoptosis.
- Active targeting suppressed tumor growth in ex vivo spheroid models.
Conclusions:
- Fabricated a multi-layered nanoparticle functionalized with a dual peptide for active tumor targeting.
- The targeted nanoparticles stimulated Pep5 activity, reducing tumor growth in vitro and ex vivo.
- This approach shows promise for overcoming peptide-based therapy targeting limitations in cancer treatment.
