Structure of micelleplexes formed between QPDMAEMA-b-PLMA amphiphilic cationic copolymer micelles and DNA of different lengths

Length-Controlled Nanofiber Micelleplexes as Efficient Nucleic Acid Delivery Vehicles

“…Luciferase exhibits luminescence in the presence of luciferin, enabling quantitation of transfection efficiency using luminescence assays that have a very low background. pGL4.51 pDNA (1 μg/mL) was added to nanofibers F3 , nanospheres S2 , and PDMAEMA 249 at an N/P ratio of 60 in HBG and aged for 24 h. The resulting micelleplexes and polyplexes were imaged via TEM (Figures and S19, S20) which revealed individual nanofibers and small aggregates of nanospheres bound to an electron-dense species, ascribed to be pDNA . Smaller electron-dense particles were also observed bound to nanofibers and nanospheres without pDNA added (number-average width W n = 1.4 nm, Đ = 1.04, σ = 0.3 nm, Figure S21).…”

“…pGL4.51 pDNA (1 μg/mL) was added to nanofibers F3, nanospheres S2, and PDMAEMA 249 at an N/P ratio of 60 in HBG and aged for 24 h. The resulting micelleplexes and polyplexes were imaged via TEM (Figures 6 and S19, S20) which revealed individual nanofibers and small aggregates of nanospheres bound to an electron-dense species, ascribed to be pDNA. 43 Smaller electron-dense particles were also observed bound to nanofibers and nanospheres without pDNA added (number-average width W n = 1.4 nm, Đ = 1.04, σ = 0.3 nm, Figure S21). These particles are ascribed to be the salt particles from the synthesis step that were previously noted (pS4).…”

“…In addition to polyplexes, several other polymeric architectures are used for NA delivery such as polyplex micelles, which contain a polyion complex core and a neutral polymeric corona, , bottlebrush polymers (termed ‘bottleplexes’), , dendrimers, PRINT hydrogels, , and micelleplexes. ,− Micelleplexes are polymer:NA complexes where the NA cargo is complexed to the corona of a polymer micelle, rather than within the particle core as is the case for a polyplex. Work by Reineke, Lodge, and co-workers has shown that spherical PDMAEMA micelleplexes can exhibit superior transfection activity to PDMAEMA polyplexes. , Despite their promise, there has been little work on the effects of micelleplex morphology, with research efforts instead focused on the development of multiresponsive, multimodal systems , or degradability . A key issue facing micelleplexes and the field of nanomedicine in general is the development of a deeper understanding of the nano-bio interface; in particular, how physicochemical properties such as the particle size, shape, and surface chemistry affect pharmacokinetics issues such as toxicity, clearance, biodistribution, and tissue specificity. ,,, To this end, precision materials must be produced and studied to uncover the effects of these parameters and serve as a guide for future delivery systems.…”

“…Work by Reineke, Lodge, and co-workers has shown that spherical PDMAEMA micelleplexes can exhibit superior transfection activity to PDMAEMA polyplexes. 41,42 Despite their promise, there has been little work on the effects of micelleplex morphology, 43 with research efforts instead focused on the development of multiresponsive, multimodal systems 38,39 or degradability. 44 A key issue facing micelleplexes and the field of nanomedicine in general is the development of a deeper understanding of the nano-bio interface; in particular, how physicochemical properties such as the particle size, shape, and surface chemistry affect pharmacokinetics issues such as toxicity, clearance, biodistribution, and tissue specificity.…”

Hydrophilic Random Cationic Copolymers as Polyplex-Formation Vectors for DNA

“…PDMAEMA exhibits less cytotoxicity compared with other cationic polymers and enhanced transfection efficiency [ 25 , 26 , 27 ]. Furthermore, the controllable synthetic preparation with tunable molecular characteristics [ 25 ] and various macromolecular architectures using controlled radical polymerization methodologies [ 6 , 25 , 26 ], the easy functionalization of its tertiary amine for high-binding affinity to nucleic acids [ 27 , 28 ], and the stimuli-responsive behavior to pH and temperature [ 29 , 30 , 31 ] render PDAEMA even more attractive for its utilization as a gene transfection vector. However, the cationic nature of PDMAEMA bears cytotoxicity issues [ 12 , 26 ] and colloidal instability [ 25 ] which are the major limiting factors for in vivo application.…”