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pH-Responsive Dynaplexes as Potent Apoptosis Inductors by Intracellular Delivery of Survivin siRNA
Biomacromolecules. 2023 Jul 31. doi: 10.1021/acs.biomac.3c00424. Online ahead of print.ABSTRACTGene knockdown by siRNA offers an unrestricted choice of targets and specificity based on the principle of complementary Watson-Crick base pairing with mRNA. However, the negative charge, large molecular size, and susceptibility to enzymatic degradation of siRNA impede its successful transfection, hence limiting its potential for therapeutic use. The development of efficient and safe siRNA transfection agents is, therefore, critical for siRNA-based therapy. Herein, we developed a protein-based biodynamic polymer (biodynamer) that...
Source: Biomacromolecules - July 31, 2023 Category: Biochemistry Authors: Yun Liu Salma Ashmawy Lorenz Latta Agnes-Valencia Weiss Alexander F Kiefer Sarah Nasr Brigitta Loretz Anna K H Hirsch Sangeun Lee Claus-Michael Lehr Source Type: research

Hydroxyl-Rich PGMA-Based Cationic Glycopolymers for Intracellular siRNA Delivery: Biocompatibility and Effect of Sugar Decoration Degree.
Abstract The ErbB family of proteins, structurally related to the epidermal growth factor receptor (EGFR), is found to be over-expressed in many cancers such as gliomas, lung and cervical carcinomas. Gene therapy allows to modify the expression of genes like ErbB and has been a promising strategy to target oncogenes and tumor suppressor genes. In the current work, novel hydroxyl-rich polyglycidyl methacrylate (PGMA)-based cationic glycopolymers were designed for intracellular small interfering RNA (siRNA) delivery to silence the EGFR gene. The cationic polymers with different sugar decoration degrees (0%, 9%, and ...
Source: Biomacromolecules - April 9, 2019 Category: Biochemistry Authors: Chen Y, Diaz-Dussan D, Peng YY, Narain R Tags: Biomacromolecules Source Type: research

Acid degradable cationic galactose-based hyperbranched polymers as nano-therapeutic vehicles for Epidermal Growth Factor Receptor (EGFR) knockdown in Cervical Carcinoma.
In this study we synthetized by reversible addition-fragmentation chain transfer (RAFT) polymerization, several acid degradable galactose-based hyperbranched cationic polymers with varying molecular weights (10 to 20 kDa) and compositions with 2-lactobioamidoethyl methacrylamide [LAEMA] and 2- aminoethyl methacrylamide hydrochloride [AEMA] at different ratios (2.0, 1.0 & 0.5) and evaluated their ability to enhance Epidermal Growth Factor Receptor (EGFR) knockdown in cervical carcinoma. All the polymer constructs have enhanced capabilities to condensate siRNA (short interfering RNA), showing low toxicity at higher LAEMA...
Source: Biomacromolecules - August 29, 2018 Category: Biochemistry Authors: Peng YY, Diaz-Dussan D, Kumar P, Narain R Tags: Biomacromolecules Source Type: research

Galactose Derivative-Modified Nanoparticles for Efficient siRNA Delivery to Hepatocellular Carcinoma.
In this study, we assembled lipid/calcium/phosphate nanoparticles (LCP NPs) conjugated with eight types of galactoside derivatives and demonstrated that phenyl β-d-galactoside-decorated LCP NPs (L4-LCP NPs) exhibited a superior siRNA delivery into HCC cells compared to normal hepatocytes. VEGF siRNAs delivered by L4-LCP NPs downregulated VEGF expression in HCC in vitro and in vivo and led to a potent antiangiogenic effect in the tumor microenvironment of a murine orthotopic HCC model. The efficient delivery of VEGF siRNA by L4-LCP NPs that resulted in significant tumor regression indicates that phenyl galactoside could be...
Source: Biomacromolecules - May 29, 2018 Category: Biochemistry Authors: Huang KW, Lai YT, Chern GJ, Huang SF, Tsai CL, Sung YC, Chiang CC, Hwang PB, Ho TL, Huang RL, Shiue TY, Chen Y, Wang SK Tags: Biomacromolecules Source Type: research

Self-assembled Polypeptide Nanogels with Enzymatically Transformable Surface as an siRNA Delivery Platform.
Abstract Nanometer-size gel particles, or nanogels, have potential for delivering therapeutic macromolecules. A cationic surface promotes cellular internalization of nanogels but undesired electrostatic interactions, such as with blood components, cause instability and toxicities. Polyethylene glycol coating has been used to shield charges, but this decreases delivery efficiency. Technical difficulties in synthesis and controlling molecular weights make it unfeasible to, instead, coat with biodegradable polymers. Our proposed solution is cationized nanogels enzymatically functionalized with branched polysaccharide...
Source: Biomacromolecules - October 23, 2017 Category: Biochemistry Authors: Nishimura T, Yamada A, Umezaki K, Sawada SI, Mukai SA, Sasaki Y, Akiyoshi K Tags: Biomacromolecules Source Type: research

Amphipathic Homopolymers for siRNA Delivery: Probing Impact of Bifunctional Polymer Composition on Transfection.
In this study, we systematically explore the influence of the lipophilic group on the siRNA transfection properties of the polycationic-based delivery vectors. For this, a novel and modular synthetic strategy was developed for the preparation of polymers carrying a cationic site and a lipophilic group at each polymer repeat unit. These bifunctional polymers could form a complex with siRNA and deliver it to human colon carcinoma cells (HT-29-luc). In general, transfection capability increased with an increase in the chain length of the lipophilic moiety. The best transfection agent, a polymer containing ammonium groups and ...
Source: Biomacromolecules - April 22, 2014 Category: Biochemistry Authors: Buerkli C, Lee SH, Moroz E, Stuparu MC, Leroux JC, Khan A Tags: Biomacromolecules Source Type: research

The influence of oligospermine architecture on their suitability for siRNA delivery.
Abstract Spermines are naturally abundant polyamines, which partially condense nucleic acids and exhibit the "proton-sponge effect" in an acidic environment. However, spermine shows limited transfection efficiency of nucleic acids due to its low molecular weight. Therefore, spermines need to be modified to be used as non-viral vectors for nucleic acids. Here, we synthesized linear bisspermine, and linear and dendritic tetraspermine with different molecular architecture. These oligospermines have been self-assembled into polyplexes with siRNA. The structure-activity relationship of the oligospermines was evaluated ...
Source: Biomacromolecules - February 19, 2014 Category: Biochemistry Authors: Elsayed M, Corrand V, Kolhatkar V, Xie Y, Kim NH, Kolhatkar R, Merkel OM Tags: Biomacromolecules Source Type: research