Amphiphilic peptide dendrimer-based nanovehicles for safe and effective siRNA delivery
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Biophysics Reports
R E S E A RC H A RT I C L E
Amphiphilic peptide dendrimer-based nanovehicles for safe and effective siRNA delivery Chi Ma1, Dandan Zhu1, Yu Chen1, Yiwen Dong1, Wenyi Lin1, Ning Li1, Wenjie Zhang1, Xiaoxuan Liu1& 1
State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing 210009, China
Received: 28 July 2020 / Accepted: 18 September 2020 / Published online: 21 November 2020
Abstract
Small interfering RNA (siRNA)-based RNA interference has emerged as a promising therapeutic strategy for the treatment of a wide range of incurable diseases. However, the safe and effective delivery of siRNA therapeutics into the interior of target cells remains challenging. Here, we disclosed novel amphiphilic peptide dendrimers (AmPDs) that composed of hydrophobic two lipid-like alkyl chains and hydrophilic poly(lysine) dendrons with different generations (2C18-KK2 and 2C18-KK2K4) as nanovehicles for siRNA delivery. These AmPDs are able to self-assemble into supramolecular nanoassemblies that are capable of entrapping siRNA molecules into nanoparticles to protect siRNA from enzymatic degradation and promote efficient intracellular uptake without evident toxicity. Interestingly, by virtue of the optimal balance of hydrophobic lipid-like entity and hydrophilic poly(lysine) dendron generations, AmPD 2C18-KK2K4 bearing bigger hydrophilic dendron can package siRNA to form stable, but more ready to disassemble complexes, thereby resulting in more efficient siRNA releasing and better gene silencing effect in comparison with AmPD 2C18-KK2 bearing smaller dendron. Additional studies confirmed that 2C18-KK2K4 can capitalize on the advantages of lipid and peptide dendrimer vectors for effective siRNA delivery. Collectively, our AmPD-based nanocarriers indeed represent a safe and effective siRNA delivery system. Our findings also provide a new perspective on the modulation of selfassembly amphiphilic peptide dendrimers for the functional and adaptive delivery of siRNA therapeutics.
Keywords Amphiphilic peptide dendrimer, Supramolecular nanoassemblies, RNA interference, siRNA delivery
INTRODUCTION Small interfering RNA (siRNA), a double-stranded RNA molecule with 19–23 nucleotides, has the powerful capacity to silence the expression of any gene, such as disease-linked genes, with complementary mRNA
Chi Ma and Dandan Zhu have contributed equally to this work.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s41048-020-00120-z) contains supplementary material, which is available to authorized users. & Correspondence: [email protected] (X. Liu)
278 | December 2020 | Volume 6 | Issue 6
sequence via Watson–Crick base pairing (Bajan and Hutvagner 2020; Castanotto and Rossi 2009; Weng et al. 2019). SiRNA-based RNA interference (RNAi) (Castanotto and Rossi 2009; Kay 2015; Setten et al. 2019; Wittrup and Lieberman 2015) is exploited as a p
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