Bifunctional and Bioreducible Dendrimer Bearing a Fluoroalkyl Tail for Efficient Protein Delivery Both In Vitro and In Vivo
- 6 November 2020
- journal article
- research article
- Published by American Chemical Society (ACS) in Nano Letters
- Vol. 20 (12), 8600-8607
- https://doi.org/10.1021/acs.nanolett.0c03287
Abstract
Rational design of stimuli-responsive polymers for cytosolic protein delivery with robust efficiency is of great importance but remains a challenging task. Here, we reported a bioreducible and amphiphilic dendrimer bearing a fluoroalkyl tail for this purpose. The fluorolipid was conjugated to the focal point of a cysteamine-cored polyamidoamine dendrimer via disulfide bond, while phenylboronic acid moieties were decorated on dendrimer surface for efficient protein binding. The yielding polymer showed high protein binding capability and complex stability and could efficiently release the cargo proteins in a glutathione-responsive manner. The designed polymer was effective in the delivery of various membrane-impermeable proteins into living cells with reserved bioactivities. In addition, the polymer efficiently delivered a toxin protein saporin into 4T1 breast cancer cells and inhibited the tumor growth in vivo after intravenous injection. The developed polymer in this study is a promising vector for the delivery of membrane-impermeable proteins to treat various diseases.Keywords
Funding Information
- Ministry of Science and Technology of the People's Republic of China (2019YFA0904500)
- China Postdoctoral Science Foundation (2020M672609)
- National Natural Science Foundation of China (21725402, 22005101)
- Guangdong Provincial Key Laboratory of Functional and Intelligent Hybrid Materials and Devices (2019B121203003)
This publication has 71 references indexed in Scilit:
- Strategies in the delivery of Cas9 ribonucleoprotein for CRISPR/Cas9 genome editingTheranostics, 2021
- Engineered Interactions with Mesoporous Silica Facilitate Intracellular Delivery of Proteins and Gene EditingNano Letters, 2020
- Rational Design of Nanocarriers for Intracellular Protein DeliveryAdvanced Materials, 2019
- Reversible Click Chemistry for Ultrafast and Quantitative Formation of Protein–Polymer Nanoassembly and Intracellular Protein DeliveryACS Nano, 2019
- Protein Delivery into the Cell Cytosol using Non-Viral NanocarriersTheranostics, 2019
- Recent Advances in Anti-cancer Protein/Peptide DeliveryBioconjugate Chemistry, 2018
- Protein Nanotherapeutics as an Emerging Modality for Cancer TherapyAdvanced Healthcare Materials, 2018
- Peptide and protein nanoparticle conjugates: versatile platforms for biomedical applicationsChemical Society Reviews, 2018
- Tailoring nanocarriers for intracellular protein deliveryChemical Society Reviews, 2011
- Protein therapeutics: a summary and pharmacological classificationNature Reviews Drug Discovery, 2008