Combinatorially synthesized materials, especially cationic polymers (CPs), with gene transfection function hold great promise in nanotechnology. However, the main limitations of the existing CPs [such as polyethylenimine (PEI), poly-L-arginine, or polyamidoaminebased dendrimers] as gene transfection agents are high cytotoxicity in the physiological environment. We have developed novel CPs composed of polyaminesendogeneous tetraamine spermine (Spm) and synthetically made triamine N-(2-aminoethyl)-1,3-propanediamine (Apd) for incorporating sec-amino groups and imparting PEI-like structure to the CP backbones. Naturally occurring building blocks such as amino acid arginine (R) was also used for incorporating guanidine-groups into the CPs. The cytotoxicity of resulting CPspolyureas (PUs) and polyamides such as polysuccinamides and R-attached polymalamides was evaluated using murine and human fibroblasts and carcinoma cell lines. The cell compatibility screening revealed that the CPs made of Apd are less cytotoxic compared to Spm-based analogues. From the novel polymer library, total of six polymers were further studied for oligonucleotide (pDNA) complexation and transfection abilities. Highly water-soluble CPs formed nano-sized polyplexes with pDNA at rather low CP/pDNA weight ratios and showed less cytotoxicity and higher transfection ability compared to widely used PEI as well as commercially available transfection agents. Furthermore, new CPs showed selective transfection activity toward certain cell lines (4T1, HeLa, NIH3T3, and CCD 27SK), which is important for their potential applications in gene therapy.

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High-molecular-weight AA-BB-type aliphatic polyesters were synthesized via Cu(I)-catalyzed click step-growth polymerization (SGP) following a new synthetic strategy. The synthesis was performed between diyne and diazide monomers in an organic solvent as one pot process using three components and two stages. The dipropargyl esters of dicarboxylic acids (component 1) were used as diyne monomers, di-(bromoacetic acid)-alkylene diesters (component 2) were used as precursors of diazide monomers, and sodium azide (component 3) was used for generating diazide monomers. The SGP was carried out in two steps: at Step 1 dibromoacetates interacted with two moles of sodium azide resulting in diazide monomers which interacted in situ with diyne monomers atStep 2 in the presence of Cu(I) catalyst. A systematic study was done for optimizing the multiparameter click SGP in terms of the solvent, duration of both Step 1 and Step 2, solution concentration, catalyst concentration, catalyst and catalyst activator (ligand) nature, catalyst/ligand mole ratio, and temperature of both steps of the click SGP. As a result, high-molecular-weight ( 푊 up to 74 kDa) elastic film-forming click polyesters were obtained. The new polymers were found suitable for fabricating biodegradable nanoparticles, which are promising as drug delivery containers in nanotherapy.

New biodegradable amino acid based biodegradable (AABB) ester polymers having a potential for constructing resorbable surgical and therapeutical devices were synthesized by solution step-growth polymerization (SGP) of bis-azlactones (BALs) with dip -toluenesulfonic acid salts of bis-(α-amino acid)-α,ω-alkylene diesters (TDADEs). Relatively low-molecularweight homopolymers-poly(ester amide)s with Mw within 2,800-19,600 Da (GPC in DMF) were obtained. To increase molecular weights of the goal AABB ester polymers two additional synthetic strategies were appliedeither activated diester such as dip -nitrophenyl sebacate was used as a comonomer of BAL, or alkylene diamine such as 1,6-hexamethylenediamine was used as a comonomer of TDADE. As a result high-molecular-weight AABB ester polymers with Mw up to 103,500 Da were synthesized depending on co-monomers' structure and mole ratios. All the BAL-based polymers obtained after SGP were practically[J1] amorphous. The thermograms (DSC) of the polymers made of the BAL F showed wide endotherms within 55-120 o C. These endotherms were assigned to melting hydrophobic domains formed by highly hydrophobic fragments-residues of phenylalanine-based bis-azlactone (BAL F) in the polymeric backbones. The obtained new BAL-based ester polymers substantially expands a family of AABB polymers destined for constructing resorbable surgical and pharmaceutical devices.

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