Cited by 39RNA Interference and Gene DeliveryNanoparticle-Based Drug DeliveryDendrimers and Hyperbranched Polymers

ScFv‐Decorated PEG‐PLA‐Based Nanoparticles for Enhanced siRNA Delivery to Her2+ Breast Cancer

Dou, Shuang, Yang, Xian‐Zhu, Xiong, Meng‐Hua, Sun, Chun‐Yang, Yao, Yan‐Dan, Zhu, Yan‐Hua, Wang, Jun·2014·Advanced Healthcare Materials

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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Crossref · 10.1002/adhm.201400037

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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
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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