A general strategy to improve the transfection efficiency as well as lower the cytotoxicity for polycationic vectors has been developed. Through the polycondensation addition of N,N'-methylene bisacrylamide and 1-(2-aminoethyl)piperazine in a water/N,N-dimethylformamide cosolvent, a series of cationic poly(amido amine)s with same repeating units but different branched architecture have been prepared. With the increase in branched architecture, the cationic polymers become more and more compact, accompanied by the enhancement of primary and tertiary amino groups. Therefore, the buffering capacities and DNA condensation capabilities of cationic poly(amido amine)s are strengthened greatly, whereas the correspondent cytotoxicity decreases. Correspondingly, the transfection efficiency is improved by more than three orders of magnitude. The results of this study indicate that the gene delivery can be readily regulated by only changing the branched architecture of polycations.
The utilization of nanotechnology for the delivery of a wide range of anticancer drugs has the potential to reduce adverse effects of free drugs and improve the anticancer efficacy. However, carrier materials and/or chemical modifications associated with drug delivery make it difficult for nanodrugs to achieve clinical translation and final Food and Drug Administration (FDA) approvals. We have discovered a molecular recognition strategy to directly assemble two FDA-approved small-molecule hydrophobic and hydrophilic anticancer drugs into well-defined, stable nanostructures with high and quantitative drug loading. Molecular dynamics simulations demonstrate that purine nucleoside analogue clofarabine and folate analogue raltitrexed can self-assemble into stable nanoparticles through molecular recognition. In vitro studies exemplify how the clofarabine:raltitrexed nanoparticles could greatly improve synergistic combination effects by arresting more G1 phase of the cell cycle and reducing intracellular deoxynucleotide pools. More importantly, the nanodrugs increase the blood retention half-life of the free drugs, improve accumulation of drugs in tumor sites, and promote the synergistic tumor suppression property in vivo.
The ever-growing demand for wearable electronic devices is stimulating the development of novel materials for fabrication of flexible electronics. Among all promising candidates, polysaccharide-based hydrogels are constructing a prospective pattern for achieving flexible electronic functionalities, benefiting from their ecofriendliness, renewability, biodegradability, and sustainability. However, one of the most important drawbacks of these hydrogels is slow self-healing. To address the abovementioned issue, we propose a simple method to fabricate a starch-based (starch/polyvinyl alcohol (PVA)/borax, SPB) conductive hydrogel. Due to the dual reversible interactions of hydrogen bonding and the boronic ester linkages, the hydrogel presents enhanced mechanical performance and ultrafast selfhealing ability both in air and underwater. The mechanical properties recover within 10 s in air and within 120 s underwater, and the electronic functionality recovers within 90 ms in air and within 110 ms underwater. In addition, the abovementioned two interactions also endow the hydrogel with reversible sol−gel transition properties, which allow the hydrogel to be reused repeatedly. Due to large amounts of Na + and free B(OH) 4 − ions, the hydrogel showed great conductivity and may work as strain sensor with high sensitivity (GF = 1.02 at 110−200% strains). The ionic hydrogel sensor could rapidly (≤180 ms) perceive human motions, even very small motions such as swallowing and pronunciation. With the combination of these seductive features, such an ecofriendly polysaccharide-derived hydrogel prepared through a facile and green preparation process would have great potential application for sustainable wearable sensors.
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