Multifunctional polyion complex micelle featuring enhanced stability, targetability, and endosome escapability for systemic siRNA delivery to subcutaneous model of lung cancer

Drug Delivery and Translational Research
Hyun Jin KimKazunori Kataoka

Abstract

For systemic small interfering RNA (siRNA) delivery to tumor mass, a multifunctional polyion complex micelle was constructed with a block copolymer bearing a targeting ligand and a micelle-stabilizing moiety as well as an endosome-disrupting cationic unit. The block copolymer was comprised of poly(ethylene glycol) (PEG) and a polyaspartamide derivative with flanking cationic tetraethylenepentamine (TEP) moiety (PAsp(TEP)), in which the distal ends of PEG and PAsp(TEP) were further installed with cyclic RGD (cRGD) peptide ligand and cholesteryl (Chol) moiety, respectively. The resulting polymer was confirmed to form siRNA-loaded micelle with a diameter of sub 50 nm and a narrow size distribution. In the stability assays with fluorescently labeled siRNA, the terminal Chol moiety significantly suppressed both the rapid dissociation of the micelles in the serum-containing medium and their rapid elimination from the bloodstream, presumably due to its hydrophobic interactions in the micellar core. Moreover, the targeting cRGD ligand, associated with the stabilizing moiety, significantly enhanced the accumulation of siRNA-loaded micelle in a subcutaneous lung (A549) tumor, compared to a non-targeted control, after systemic administrat...Continue Reading

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Citations

Jan 21, 2016·Expert Opinion on Drug Delivery·Wajd Amly, Rafik Karaman
Jul 6, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Horacio Cabral, Kazunori Kataoka
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Sep 21, 2018·Expert Opinion on Drug Delivery·Mariana MagalhãesFrancisco Veiga
Feb 9, 2020·Nature Reviews. Clinical Oncology·John D MartinRakesh K Jain
Sep 3, 2020·Polymers·Jose Rodrigo MaganaIlja K Voets
Jun 30, 2016·Advanced Drug Delivery Reviews·Hyun Jin KimKazunori Kataoka
Jun 13, 2020·International Journal of Pharmaceutics·Evangelos GeorgilisElisabeth Garanger
Jun 5, 2021·Materials Science & Engineering. C, Materials for Biological Applications·Nidhi RavalRakesh K Tekade
Mar 16, 2017·ACS Nano·Beatriz PelazWolfgang J Parak
Jun 30, 2018·Chemical Reviews·Horacio CabralKazunori Kataoka

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