Nanoassemblies with Effective Serum Tolerance Capability Achieving Robust Gene Silencing Efficacy for Breast Cancer Gene Therapy
- 23 December 2020
- journal article
- research article
- Published by Wiley in Advanced Materials
- Vol. 33 (7), e2003523
- https://doi.org/10.1002/adma.202003523
Abstract
The transfection efficiency of siRNA mediated by cationic polymers is limited due to the instability of polymers/siRNA complexes in the presence of serum. Poly(ethylene glycol) (PEG) is usually applied to modify cationic polymers, so as to reduce protein and cell adsorption and then to improve siRNA transfection efficiency. However, the polymers’ modification with PEG mostly consumes the free amino of the polymers, which can, in turn, reduce the charge density and limit their siRNA transfection efficacy. Here, a new PEG modification strategy that need not consume the surface aminos of polymers is proposed. Catechol–PEG polymers are coated on the surface of phenylboronic acid (PBA)‐modified Generation 5 (G5) poly(amidoamine) dendrimers (G5PBA) via reversible boronate esters to establish PEG‐modified dendrimer/siRNA nanoassemblies for efficient siRNA delivery. The PEG/G5PBA/siRNA nanoassemblies have positive charge and show excellent gene silencing efficacy in the absence of serum in vitro. More importantly, the PEG/G5PBA/siRNA nanoassemblies also exhibit excellent serum resistance and gene silencing efficacy in serum‐containing medium. Furthermore, the effective antiserum and gene silencing efficacy elicited by these nanoassemblies lead to excellent antitumor effects in vivo. This proposed strategy constitutes an important approach to reach an excellent gene silencing efficacy in the presence of serum.Funding Information
- National Natural Science Foundation of China (21704061, 81771968)
- Shanghai Municipal Education Commission (20181705)
- Shanghai Jiao Tong University (YG2016QN54, ZH2018ZDA05)
This publication has 51 references indexed in Scilit:
- Transdermal siRNA delivery by pH-switchable micelles with targeting effect suppress skin melanoma progressionJournal of Controlled Release, 2020
- Natural Polyphenol Inspired Polycatechols for Efficient siRNA DeliveryCCS Chemistry, 2020
- Microfluidic-Based Holonomic Constraints of siRNA in the Kernel of Lipid/Polymer Hybrid Nanoassemblies for Improving Stable and Safe In Vivo DeliveryACS Applied Materials & Interfaces, 2020
- Trimethyl chitosan-hyaluronic acid nano-polyplexes for intravitreal VEGFR-2 siRNA delivery: Formulation and in vivo efficacy evaluationNanomedicine: Nanotechnology, Biology and Medicine, 2020
- Highly efficient photocontrolled targeted delivery of siRNA by a cyclodextrin-based supramolecular nanoassemblyChemical Communications, 2020
- Programing Assembling/Releasing Multifunctional miRNA Nanomedicine to Treat Prostate CancerACS Applied Materials & Interfaces, 2020
- Green Tea Catechin Dramatically Promotes RNAi Mediated by Low-Molecular-Weight PolymersACS Central Science, 2018
- Intravenous administration of brain-targeted stable nucleic acid lipid particles alleviates Machado-Joseph disease neurological phenotypeBiomaterials, 2016
- Co-delivery of doxorubicin and P-gp siRNA into human breast cancer cells by functionalized PLGA nanobubbles and ultrasound imaging in vitroJournal of Controlled Release, 2015
- Dual Targeted Immunotherapy via In Vivo Delivery of Biohybrid RNAi‐Peptide Nanoparticles to Tumor‐Associated Macrophages and Cancer CellsAdvanced Functional Materials, 2015