ScFv‐Decorated PEG‐PLA‐Based Nanoparticles for Enhanced siRNA Delivery to Her2+ Breast Cancer
Abstract
Patients with Her2‐overexpressing (Her2+) breast cancers generally have a poorer prognosis due to the high aggressiveness and chemoresistance of the disease. Small interfering RNA (siRNA) targeting the gene encoding polo‐like kinase 1 (Plk1; si Plk1) has emerged as an efficient therapeutic agent for Her2+ breast cancers. Poly(ethylene glycol)‐block‐poly(d,l‐lactide) (PEG‐PLA)‐based nanoparticles for siRNA delivery were previously developed and optimized. In this study, for targeted delivery of si Plk1 to Her2+ breast cancer, anti‐Her2 single‐chain variable fragment antibody (ScFv Her2)‐decorated PEG‐PLA‐based nanoparticles with si Plk1 encapsulation (ScFv Her2‐NP si Plk1) are developed. With the rationally designed conjugation site, ScFv Her2‐NP siRNA can specifically bind to the Her2 antigen overexpressed on the surface of Her2+ breast cancer cells. Therefore, ScFv Her2‐NP si Plk1 exhibits improved cellular uptake, promoted Plk1 silencing efficiency, and induced enhanced tumor cell apoptosis in Her2+ breast cancer cells, when compared with nontargeted NP si Plk1. More importantly, ScFv Her2‐NP siRNA markedly enhances the accumulation of siRNA in Her2+ breast tumor tissue, and remarkably improves the efficacy of tumor suppression. Dose‐dependent anti‐tumor efficacy further demonstrates that ScFv Her2‐decorated PEG‐PLA‐based nanoparticles with si Plk1 encapsulation can significantly enhance the inhibition of Her2+ breast tumor growth and reduce the dose of injected siRNA. These results suggest that ScFv Her2‐decorated PEG‐PLA‐based nanoparticles show great potential for targeted RNA interference therapy of Her2+ breast tumor.
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The hydrophilic shell on the surface of PEG-PLA micelles hinders the adsorption of plasma proteins and avoids elimination by the reticuloendothelial system, resulting in prolonged residence time in the circulation system.
“Also, the hydrophilic shell on the surface of PEG-PLA micelles is capable of hindering the adsorption of plasma proteins and avoiding the elimination by reticuloendothelial system, resulting in prolonged residence time in circulation system.39”
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DEVELOPMENT OF AMPHOTERICIN-B LOADED NANOPARTICLES AND EVALUATION THE ANTIMICROBIAL POTENCY
Öz, U. C., Rızvanoğlu, S. S., Abamor, E. Ş., CENGİZ, G., Berber, H., Derman, S., Eryılmaz, M., & Bozkır, A. (2023) · Ankara Universitesi Eczacilik Fakultesi Dergisi · doi:10.33483/jfpau.1352203
- Authors
- Dou, S., Yang, X., Xiong, M., Sun, C., Yao, Y., Zhu, Y., & Wang, J.
- Affiliations
- University of Science and Technology of China (CN)
- Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences University of Science and Technology of China Hefei Anhui 230027 P. R. China
- Corresponding author
- Wang, Jun
- ORCID
- Venue
- Advanced Healthcare Materials
- Publisher
- Wiley
- Published
- 2014-06-20
- Volume
- 3
- Issue
- 11
- Pages
- 1792-1803
- ISSN
- 2192-2640 (ISSN-L)
- 2192-2659
- OpenAlex
- W2031771095
- Cited by
- 39
- References
- 64
- Citations by year
- 2024: 4 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 7 · 2016: 6 · 2015: 5 · 2014: 1
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Advanced Healthcare Materials (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
- Keywords
- siRNA delivery, PEG-PLA nanoparticles, scFv, HER2-positive breast cancer, PLK1, nanoparticle conjugation, tumor accumulation, apoptosis, tumor suppression
- MeSH terms
- Polo-Like Kinase 1, Breast Neoplasms, Female, Humans, Polyethylene Glycols, Proto-Oncogene Proteins, Genetic Therapy, Apoptosis, Protein Serine-Threonine Kinases, Receptor, ErbB-2, Erb-b2 Receptor Tyrosine Kinases, Cell Cycle Proteins, RNA, Small Interfering, Cell Line, Tumor, Nanoparticles, Single-Chain Antibodies
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