Evaluation of Rod‐Shaped Nanoparticles as Carriers for Gene Delivery

Abstract

Fabrication of nonspherical particles for gene delivery remains a major challenge. In this study, novel rod-like nanoparticles are prepared for effi cient gene delivery by self-assembly of α-cyclodextrin (α-CD) and polyethyleniminemethoxy poly(ethylene glycol) (PEI-mPEG). The study reveals that the rod-like PEI-mPEG/α-CD particles can bind DNA effectively and the resulting PEImPEG/α-CD/DNA complexes show over four times higher gene delivery capability than their spherical counterparts and PEI(25K) due to more effi cient cellular uptake. Furthermore, the cytotoxicity of rod-like PEI-mPEG/α-CD is about fi ve times lower than that of the nanospheres, and 50 times lower than that of DNA/PEI(25K). These results indicate that shape is an important parameter for the design of gene delivery vectors. different design parameters of nonviral particles should be considered and optimized. There exists ample evidence that particle size [ 3 ] and surface chemistry [ 4 ] can dramatically infl uence gene transfection effi ciency. However, there is a striking lack of studies on the effect of particle shape on the gene delivery behavior.Recently, the importance of the shape of carriers in various biological processes has been realized. Emerging studies show that important biological processes such as biodistribution, cellular internalization, and toxicity exhibit strong dependence on shape. [ 5 ] The majority of the evidence available suggests that rod-like nanoparticles are more favorable for drug delivery applications. [ 6 ] But up to now, most nonviral gene vectors are spherical particles. There are only few reports on the gene delivery behavior of nonspherical nanoparticles, except needle-like histidine-lysine polymers, [ 7 ] inorganic nanotubes, [ 8 ] and some star-shaped polymeric vectors, [ 9 ] although actually a number of viruses are nonspherical in nature.The most prominent approach for fabricating rod-like particles has been self-assembly of amphiphilic copolymers. [ 10 ] However, preparing biocompatible rod-like particles with good DNAbinding capability via self-assembly and retention of shape in physiological conditions still remains a challenge. Most rod-like polymeric particles lack the desirable degradable components and only serve as a model system. To date, rare rod-like assemblies show potential for DNA binding, while good DNA-binding ability is necessary for a good gene delivery vector. [ 11 ] Our recent research has demonstrated that rod-coil complexes formed by CD and polymer chains could self-assemble into hollow spheres or rod-like tubes in aqueous solution by varying the rigid block length fraction. [ 12 ] Earlier research focused on the methodology and control of morphology. In this study, the work is extended to binding DNA using the self-assembly aggregates with different shapes and comparing their gene delivery capability. It was found that the particles prepared by α-cyclodextrin (α-CD) and polyethyleniminemethoxy poly(ethylene glycol) (PEI-mPEG) showed good DNA-binding ability, low cytotoxicity, an...

Fabrication of rod-like nanocapsules based on polylactide and 3,4-dihydroxyphenylalanine for a drug delivery system

“…5,6 Therefore, various rod-like nanoparticles have been prepared using liposomes, peptides, polylactide (PLA), chitosan, and other polymers. [7][8][9][10] Among them, PLAs have attracted considerable attention, due to the fact that they are synthesized from renewable resources and are nontoxic aer biodegradation, for various applications in industry, agriculture, and biomedical elds. 11,12 Up to now, many researchers have reported the preparation of nanoparticles, nanobers and nanolms based on PLA.…”

Mannosylated Cationic Copolymers for Gene Delivery to Macrophages

“…Particle shape influences the cell uptake and the rod‐like nanoparticles are more favorable for drug and gene delivery applications. [ 58,59 ] The shape of the particle strictly impacts on its internalization by macrophage. [ 60,61 ] A recent study suggested that rods are taken up by the cells more rapidly than spherical particles.…”

Nanoassemblies driven by cyclodextrin-based inclusion complexation

“…Another kind of nanoassembly was rod-like nanoparticles prepared by self-assembly of a-CD and PEG-PEI. 65 The rod-like particles can bind DNA effectively and showed over 4 times higher gene delivery capability than its spherical counterpart and PEI (25 kDa) (Fig. 18).…”

“…Fig.18Schematic illustration of the formation of DNA/PEI-PEG/a-CD nanospheres and nanorods for gene delivery 65. …”