Functionalized Layered Double Hydroxide Nanoparticles Conjugated with Disulfide-Linked Polycation Brushes for Advanced Gene Delivery

Abstract

Layered double hydroxides (LDHs) have aroused great attention as potential nanosized drug delivery carriers, but independent inorganic LDH wrapped with DNA shows very low transfection efficiency. To manipulate and control the surface properties of LDH nanoparticles is of crucial importance in the designing of LDH-based drug carriers. In this work, surface-initiated atom transfer radical polymerization (ATRP) of 2-(dimethylamino)ethyl methacrylate (DMAEMA) is employed to tailor the functionality of LDH surfaces in a well-controlled manner and produce a series of well-defined novel gene delivery vectors (termed as LDH-PDs), where a flexible three-step method was first developed to introduce the ATRP initiation sites containing disulfide bonds onto LDH surfaces. In comparison the pristine LDH particles, the resultant LDH-PDs exhibited better ability to condense plasmid DNA (pDNA) and much higher levels to delivery genes in different cell lines including COS7 and HepG2 cell lines. Moreover, the LDH-PDs also could largely enhance cellular uptake. This present study demonstrates that functionalization of bioinorganic LDH with flexible polycation brushes is an effective means to produce new LDH-based gene delivery systems.

Hierarchical layered double hydroxide nanocomposites: structure, synthesis and applications

“…Hu et al tailored the functionality of LDH surfaces through surface-initiated ATPR of 2-(dimethylamino)-ethyl methacrylates. 93 This LDH composite with the flexible polycation brushes (2-(dimethylamino)-ethyl methacrylates) demonstrated increased ability to condense plasmid DNA, and higher cellular uptake and gene transfection efficiency in COS7 and HepG2 cell lines. 93 Poly(ethylene glycol) (PEG) is considered a biocompatible polymer, and widely used to functionalise other drug delivery carriers with the aim of increasing colloidal stability and circulation time.…”

“…93 This LDH composite with the flexible polycation brushes (2-(dimethylamino)-ethyl methacrylates) demonstrated increased ability to condense plasmid DNA, and higher cellular uptake and gene transfection efficiency in COS7 and HepG2 cell lines. 93 Poly(ethylene glycol) (PEG) is considered a biocompatible polymer, and widely used to functionalise other drug delivery carriers with the aim of increasing colloidal stability and circulation time. [97][98][99] For example, Li et al synthesised anionic PEG functionalised LDH nanohybrids.…”

Synthetic Strategies for the Fabrication of Cationic Surface-Modified Cellulose Nanocrystals

“…PDMAEMA was reported to effectively condense plasmid DNA into nanoparticles to aid cellular internalization for gene delivery applications [76,77]. Taking advantage of this property, Hu and co-workers designed cationic CNC-based gene vectors by wrapping the surface of CNCs with disulphide bond-linked dense PDMAEMA brushes [78].…”

“…Low cytotoxicities, high transfection efficiencies, and good activity in inhibiting the growth of tumors and cancer cells rendered the rod-like CNCs with biocleavable PDMAEMA side-chains as good candidates for gene/drug delivery systems. PDMAEMA was reported to effectively condense plasmid DNA into nanoparticles to aid cellular internalization for gene delivery applications [76,77]. Taking advantage of this property, Hu and co-workers designed cationic CNC-based gene vectors by wrapping the surface of CNCs with disulphide bond-linked dense PDMAEMA brushes [78].…”

Anti‐Metastatic and Anti‐Angiogenic Activities of Core–Shell SiO2@LDH Loaded with Etoposide in Non‐Small Cell Lung Cancer

“…Layered double hydroxides (LDHs), known as anionic clays, can be expressed with the general formula [M II 1‐x M III x (OH) 2 ] x+ (A n− ) x/n • mH 2 O, where typically, M represents the metal and A is the interlayer anion 11. LDH has been demonstrated as a promising carrier for drug delivery, according to its expandable interlayer space, low cytotoxicity, and high biocompatibility 12, 13, 14, 15.…”