Multi-Layered PLGA-PEI Nanoparticles Functionalized with TKD Peptide for Targeted Delivery of Pep5 to Breast Tumor Cells and Spheroids
Akhil K Mohan,1,2 Minsa M,3 T R Santhosh Kumar,3 G S Vinod Kumar1 1Nano Drug Delivery Systems (NDDS), Cancer Biology Division, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, 695014, India; 2Research Centre, Department of Biotechnology, University of Kerala, Thiruvananthapuram, Ke...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2022-11-01
|
| Series: | International Journal of Nanomedicine |
| Subjects: | |
| Online Access: | https://www.dovepress.com/multi-layered-plga-pei-nanoparticles-functionalized-with-tkd-peptide-f-peer-reviewed-fulltext-article-IJN |
| _version_ | 1828073104315777024 |
|---|---|
| author | Mohan AK M M Kumar TRS Kumar GSV |
| author_facet | Mohan AK M M Kumar TRS Kumar GSV |
| author_sort | Mohan AK |
| collection | DOAJ |
| description | Akhil K Mohan,1,2 Minsa M,3 T R Santhosh Kumar,3 G S Vinod Kumar1 1Nano Drug Delivery Systems (NDDS), Cancer Biology Division, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, 695014, India; 2Research Centre, Department of Biotechnology, University of Kerala, Thiruvananthapuram, Kerala, India; 3Cancer Research Programme-1, Bio-Innovation Center (BIC), Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, 695014, IndiaCorrespondence: G S Vinod Kumar, Tel +91 471 2781217, Fax +91 471 2348096, Email gsvinod@rgcb.res.inPurpose: 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.Graphical Abstract: Keywords: peptide, Pep 5, tumor, cancer, breast |
| first_indexed | 2024-04-11T01:21:35Z |
| format | Article |
| id | doaj.art-561ec42f82524cef8d1da288034cc08d |
| institution | Directory Open Access Journal |
| issn | 1178-2013 |
| language | English |
| last_indexed | 2024-04-11T01:21:35Z |
| publishDate | 2022-11-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of Nanomedicine |
| spelling | doaj.art-561ec42f82524cef8d1da288034cc08d2023-01-03T11:15:44ZengDove Medical PressInternational Journal of Nanomedicine1178-20132022-11-01Volume 175581560079828Multi-Layered PLGA-PEI Nanoparticles Functionalized with TKD Peptide for Targeted Delivery of Pep5 to Breast Tumor Cells and SpheroidsMohan AKM MKumar TRSKumar GSVAkhil K Mohan,1,2 Minsa M,3 T R Santhosh Kumar,3 G S Vinod Kumar1 1Nano Drug Delivery Systems (NDDS), Cancer Biology Division, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, 695014, India; 2Research Centre, Department of Biotechnology, University of Kerala, Thiruvananthapuram, Kerala, India; 3Cancer Research Programme-1, Bio-Innovation Center (BIC), Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, 695014, IndiaCorrespondence: G S Vinod Kumar, Tel +91 471 2781217, Fax +91 471 2348096, Email gsvinod@rgcb.res.inPurpose: 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.Graphical Abstract: Keywords: peptide, Pep 5, tumor, cancer, breasthttps://www.dovepress.com/multi-layered-plga-pei-nanoparticles-functionalized-with-tkd-peptide-f-peer-reviewed-fulltext-article-IJNpeptidepep 5tumorcancerbreast |
| spellingShingle | Mohan AK M M Kumar TRS Kumar GSV Multi-Layered PLGA-PEI Nanoparticles Functionalized with TKD Peptide for Targeted Delivery of Pep5 to Breast Tumor Cells and Spheroids International Journal of Nanomedicine peptide pep 5 tumor cancer breast |
| title | Multi-Layered PLGA-PEI Nanoparticles Functionalized with TKD Peptide for Targeted Delivery of Pep5 to Breast Tumor Cells and Spheroids |
| title_full | Multi-Layered PLGA-PEI Nanoparticles Functionalized with TKD Peptide for Targeted Delivery of Pep5 to Breast Tumor Cells and Spheroids |
| title_fullStr | Multi-Layered PLGA-PEI Nanoparticles Functionalized with TKD Peptide for Targeted Delivery of Pep5 to Breast Tumor Cells and Spheroids |
| title_full_unstemmed | Multi-Layered PLGA-PEI Nanoparticles Functionalized with TKD Peptide for Targeted Delivery of Pep5 to Breast Tumor Cells and Spheroids |
| title_short | Multi-Layered PLGA-PEI Nanoparticles Functionalized with TKD Peptide for Targeted Delivery of Pep5 to Breast Tumor Cells and Spheroids |
| title_sort | multi layered plga pei nanoparticles functionalized with tkd peptide for targeted delivery of pep5 to breast tumor cells and spheroids |
| topic | peptide pep 5 tumor cancer breast |
| url | https://www.dovepress.com/multi-layered-plga-pei-nanoparticles-functionalized-with-tkd-peptide-f-peer-reviewed-fulltext-article-IJN |
| work_keys_str_mv | AT mohanak multilayeredplgapeinanoparticlesfunctionalizedwithtkdpeptidefortargeteddeliveryofpep5tobreasttumorcellsandspheroids AT mm multilayeredplgapeinanoparticlesfunctionalizedwithtkdpeptidefortargeteddeliveryofpep5tobreasttumorcellsandspheroids AT kumartrs multilayeredplgapeinanoparticlesfunctionalizedwithtkdpeptidefortargeteddeliveryofpep5tobreasttumorcellsandspheroids AT kumargsv multilayeredplgapeinanoparticlesfunctionalizedwithtkdpeptidefortargeteddeliveryofpep5tobreasttumorcellsandspheroids |