• Home
  • Search Results
  • ScFv-decorated PEG-PLA-based nanoparticles for enhanced siRNA delivery to Her2⁺ breast cancer.

ScFv-decorated PEG-PLA-based nanoparticles for enhanced siRNA delivery to Her2⁺ breast cancer.

Advanced healthcare materials (2014-06-21)
Shuang Dou, Xian-Zhu Yang, Meng-Hua Xiong, Chun-Yang Sun, Yan-Dan Yao, Yan-Hua Zhu, Jun Wang
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; siPlk1) 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 siPlk1 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 ScFvHer2 -decorated PEG-PLA-based nanoparticles with siPlk1 encapsulation can significantly enhance the inhibition of Her2(+) breast tumor growth and reduce the dose of injected siRNA. These results suggest that ScFvHer2 -decorated PEG-PLA-based nanoparticles show great potential for targeted RNA interference therapy of Her2(+) breast tumor.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
DAPI, for nucleic acid staining
Sigma-Aldrich
IPTG, ≥99% (TLC), ≤0.1% Dioxane
Sigma-Aldrich
5,5′-Dithiobis(2-nitrobenzoic acid), ≥98%, BioReagent, suitable for determination of sulfhydryl groups
Sigma-Aldrich
Imidazole, ACS reagent, ≥99% (titration)
Sigma-Aldrich
L-Glutamine, meets USP testing specifications, suitable for cell culture, 99.0-101.0%, from non-animal source
Sigma-Aldrich
Imidazole, ReagentPlus®, 99%
Sigma-Aldrich
Imidazole, for molecular biology, ≥99% (titration)
Sigma-Aldrich
Imidazole, puriss. p.a., ≥99.5% (GC)
Sigma-Aldrich
L-Glutamine, ReagentPlus®, ≥99% (HPLC)
Sigma-Aldrich
5,5′-Dithiobis(2-nitrobenzoic acid), ReagentPlus®, 99%
SAFC
L-Glutamine
Sigma-Aldrich
Imidazole, BioUltra, ≥99.5% (GC)
Sigma-Aldrich
Isopropyl β-D-1-thiogalactopyranoside, ≥99% (TLC)
Sigma-Aldrich
Imidazole buffer Solution, BioUltra, 1 M in H2O
Sigma-Aldrich
DL-Glyceraldehyde 3-phosphate solution, 45-55 mg/mL in H2O
Sigma-Aldrich
Isopropyl β-D-thiogalactopyranoside solution, ReadyMade IPTG solution for Blue-white screening
Sigma-Aldrich
Imidazole, anhydrous, free-flowing, Redi-Dri, ACS reagent, ≥99%
SAFC
Isopropyl β-D-1-thiogalactopyranoside
Sigma-Aldrich
L-Glutamine, BioUltra, ≥99.5% (NT)
Sigma-Aldrich
Imidazole, ≥99% (titration), crystalline
Sigma-Aldrich
L-Glutamine, γ-irradiated, BioXtra, suitable for cell culture
Sigma-Aldrich
Imidazole, BioUltra, for molecular biology, ≥99.5% (GC)
Supelco
Imidazole, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
L-Glutamine, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Imidazole, ReagentPlus®, 99%, Redi-Dri, free-flowing
USP
Imidazole, United States Pharmacopeia (USP) Reference Standard
Supelco
L-Glutamine, certified reference material, TraceCERT®
Sigma-Aldrich
L-Glutamine
Imidazole, European Pharmacopoeia (EP) Reference Standard
Ondansetron impurity E, European Pharmacopoeia (EP) Reference Standard