Multifunctional Glyco‐Nanofibers: siRNA Induced Supermolecular Assembly for Codelivery In Vivo

Abstract

Targeted codelivery and controlled release of drug/siRNA (small interfering RNA) in a safe and effective vehicle hold great promises for overcoming drug resistance and optimal efficacy in cancer treatment; however, rational design and preparation of such vehicles remain a critical challenge. Thus, glyco‐nanofibers (GNFs) are fabricated via supermolecular assembly of polyanionic siRNA and cationic vesicles to simultaneously deliver siRNA and doxorubicin hydrochloride (DOX) in vitro and in vivo. The vesicles are created through self‐assembly of a positively charged amphiphilic lactose derivative featuring a lactose moiety and a ferrocenium unit on either end of the molecule. The GNFs display excellent biocompatibility, enhanced cell‐penetrating ability, and hepatoma targetability. The high transport efficiency of siRNA, effective gene silencing ability, and enhanced cytotoxicity to HepG2 cells of GNFs loaded with DOX are observed in vitro. Furthermore, in vivo experiments show reduced systemic toxicity and enhanced therapeutic efficacy of DOX to both HepG2 and HepG2/ADR subcutaneous tumor‐bearing nude mice. This work proves the electrostatic self‐assembly between cationic carbohydrates and polyanionic siRNA to be a convenient and effective strategy to fabricate a single vehicle for safe and effective codelivery of drug/siRNA, which can be used to combine chemo‐ and gene‐therapy against cancers and other diseases.

Facile fabrication of hypericin-entrapped glyconanoparticles for targeted photodynamic therapy

“…Subsequently, lactose, which can specifically interact with asialoglycoprotein receptors (ASGP-R), was conjugated to the PDA surface of the asfabricated PDA-Hy-MNP composite nanoparticles (PHMs) through Michael addition or Schiff base reaction under alkaline condition. [34][35][36] The final fabricated Hy-entrapped glyconanoparticles (denoted as Lac-PHMs) have the following properties: excellent stability and dispersibility in aqueous environment, fair targeting ability for ASGP-R-overexpressing cancer cells, negligible cytotoxicity in the absence of light, and a satisfying performance in PDT. Furthermore, the strategy we designed for Hy delivery is very versatile and easily expandable, with not only Hy being replaceable by other hydrophobic PSs, but the conjugated targeting moieties, and the scaffold as well, to perform different functions.…”

<p>A multifunctional supramolecular vesicle based on complex of cystamine dihydrochloride capped pillar[5]arene and galactose derivative for targeted drug delivery</p>

“…The mixture was ultrasonicated for 30 min and left to stand for 6 h, then subjected to dialysis (molecular weight cutoff 8,000–14,000) in distilled water. DOX-loaded vesicles were obtained when no DOX detected in the water outside the dialysis tube 44…”

“…The relative cytotoxicity of unloaded vesicles, DOX and DOX-loaded vesicles were evaluated in vitro by MTT assay, respectively. MTT assay procedures refer to our previous work 44…”

Molecular engineering of polymeric supra-amphiphiles

“…26,27 Owing to their promising use in drug loading and release, redox-responsive assemblies have attracted wide interest. 28 When treated by reductants or oxidants, organic selenium compounds exhibit strong redox activity and are therefore good candidates for redox-responsive materials. 3 Through the electrostatic interactions of selenium-containing surfactant and PEG-b-PAA, a side-chain polymeric supra-amphiphile was prepared by Xu and Wang, which further assembled into micelles in water (Fig.…”