A one-step synthesis strategy based on aza-Michael reaction of poly(ethylene glycol) diacrylate (PEGDA) or PEGDA/1,6-hexanediol diacrylate (HDDA) mixture and cystamine was employed to fabricate injectable, biocompatible and degradable novel poly(-amino ester) (PBAE) hydrogels.The gelation was monitored by real-time dynamic rheological measurements in order to follow formation of the PBAE hydrogel networks. The obtained hydrogels were responsive to both pH and redox state which enabled the control of swelling, degradation and release properties by external triggers. Degradation products of the hydrogels were shown to have no significant cytotoxicity on A549 adenocarcinomic human alveolar basal epithelial cells and MCF-7 human breast cancer cells. The hydrogels were loaded with a photosensitizer, methylene blue (MB), as a model compound by simply adding the MB molecules into the precursor mixture. The activity of released MB was assessed by in vitro photodynamic therapy (PDT) studies conducted with A549 cells.

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Novel phosphonic acid-functionalized poly(amido amine) (PAA) macromers are synthesized through aza-Michael addition of 2-aminoethyl phosphonic acid or its mixture with 5-amino-1pentanol at different ratios onto N,N′ -methylene bis(acrylamide) to control the amount of phosphonic acid functionality. The macromers were homo-and copolymerized with 2hydroxyethyl methacrylate at different ratios to obtain hydrogels with various hydrophilicities.The hydrogels' swelling, biodegradation and mineralization properties were evaluated. The swelling and degradation rates of the gels can be tuned by the chemical structure of PAA macromer precursors as well as pH and CaCl2 pre-treatment. The hydrogels show compositiondependent mineralization in SBF and 5xSBF, as evidenced from Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDX) analyses. The degradation products of the hydrogels have no effect on U-2 OS, Saos-2 and NIH 3T3 cells, suggesting their cytocompatibility. Overall, these materials have potential to be used as nontoxic degradable biomaterials.

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Osteosarcoma is aggressive bone cancer, whose treatment has not changed significantly for the past few decades. Although gene therapy methods have emerged as potential treatment routes, the need for efficient and nontoxic gene delivery systems targeting osteosarcoma cells remains a challenge. Highmolecular-weight poly(ethyleneimine)s (PEIs) are used as universal transfection agents; however, they cause significant cytotoxicity. On the other hand, poly(amido amine)s (PAAs) are biocompatible, biodegradable polymers with promising transfection efficiency, which should be improved further. In this paper, we combined low-molecular-weight branched PEI (1800 Da) and PAA macromers functionalized with various amounts of (bis)phosphonic acid groups and pentanol (via 5-amino-1-pentanol (AP)). The (bis)phosphonic acid groups on these polymers (PAEIs) are intended to facilitate bone targeting. The molecular weights of the PAEI polymers were between 2600 and 8600 g/mol. Their cytotoxicities and green fluorescence protein (GFP) transfection efficiencies were tested on an osteosarcoma cell line (U-2 OS cells), which is challenging to transfect, and healthy muscle cells (C2C12). Both the cytotoxicity and transfection efficiency of PAEIs were affected by the phosphonic acid (via APA, 2-aminoethyl phosphonic acid) or bisphosphonic acid (via ALE, sodium alendronate) content of the polymers. PAEIs are more cytocompatible than both linear and branched 25 kDa PEI. ALE-containing PAEIs provided better transfection than APA-containing ones. The most efficient PAEI polymer, containing a 0.7:0.3 AP/ALE ratio, displayed a transfection efficiency that was five times higher than that of 25 kDa PEI with dramatically better cytocompatibility. This is comparable to FuGENE, but PAEI is more advantageous in selective transfection of the U-2 OS. This set of polymers may be promising candidates for targeted gene therapy of osteosarcoma.