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Source: Biomacromolecules

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Total 92 results found since Jan 2013.

Pluronic Micelle-Mediated Tissue Factor Silencing Enhances Hemocompatibility, Stemness, Differentiation Potential, and Paracrine Signaling of Mesenchymal Stem Cells
Biomacromolecules. 2021 Apr 5. doi: 10.1021/acs.biomac.1c00070. Online ahead of print.ABSTRACTMesenchymal stem/stromal cells (MSCs) evoke great excitement for treating different human diseases due to their ability to home inflamed tissues, suppress inflammation, and promote tissue regeneration. Despite great promises, clinical trial results are disappointing as allotransplantation of MSCs trigger thrombotic activity and are damaged by the complement system, compromising their survival and function. To overcome this, a new strategy is presented by the silencing of tissue factor (TF), a transmembrane protein that mediates pr...
Source: Biomacromolecules - April 5, 2021 Category: Biochemistry Authors: Vignesh K Rangasami Ganesh Nawale Kenta Asawa Sandeep Kadekar Sumanta Samanta Bo Nilsson Kristina N Ekdahl Susanna Miettinen J öns Hilborn Yuji Teramura Oommen P Varghese Oommen P Oommen Source Type: research

Systemic Delivery of NAC-1 siRNA by Neuropilin-Targeted Polymersomes Sensitizes Antiangiogenic Therapy of Metastatic Triple-Negative Breast Cancer.
Abstract Antiangiogenic therapy with bevacizumab while being interesting for metastatic triple-negative breast cancer (mTNBC) is restrained by tumor hypoxia elevation and cancer stem cell enrichment. Here, we find that neuropilin-1 (NRP-1)-targeted delivery of nucleus accumbens-associated protein-1 (NAC-1) siRNA mediated by tLyP-1 peptide-functionalized chimaeric polymersomes (tLyP-1-Ps) effectively sensitizes antiangiogenic therapy of mTNBC in vivo. tLyP-1-Ps showed good encapsulation (up to 14.4 wt. %) of siNAC-1, giving robust tLyP-1-Ps-siNAC-1 nanoformulation with a defined size of 48.5 nm (PDI = 0.13) and a s...
Source: Biomacromolecules - November 11, 2020 Category: Biochemistry Authors: Wang H, Wang X, Zhang Y, Cheng R, Yuan J, Zhong Z Tags: Biomacromolecules Source Type: research

Recent Advances of Polycationic siRNA Vectors for Cancer Therapy.
Abstract Small interfering RNAs (siRNAs) have recently emerged as a new class of biopharmaceuticals for the treatment of various diseases, including genetic diseases, viral infections, heritable disorders, and most prominently, cancer. However clinical applications of siRNA-based therapeutics through intravenous administration have been limited due to their rapid degradation and renal clearance, poor cellular uptake, low cytoplasmic release by escaping endocytic uptake and off-target effects. The success of siRNA-based therapeutics depends upon the design and creation of efficient delivery vectors that should be a...
Source: Biomacromolecules - June 21, 2020 Category: Biochemistry Authors: Bholakant R, Qian H, Zhang J, Huang X, Huang D, Feijen J, Zhong Y, Chen W Tags: Biomacromolecules Source Type: research

Tackling the Limitations of Copolymeric Small Interfering RNA Delivery Agents by a Combined Experimental-Computational Approach.
In this study, we tackle the drawbacks of the existing systems by a combined experimental-computational in-depth investigation of the influence of the polymer architecture over the binding and transfection efficiency. For that purpose, a library of diblock copolymers with a molar mass of 30 kDa and a narrow dispersity (Đ < 1.12) was synthesized. We studied in detail the impact of an altered block size and/or composition of cationic diblock copolymers on the viability of each respective structure as a delivery agent for polynucleotides. The experimental investigation was further complemented by a computational study emp...
Source: Biomacromolecules - November 3, 2019 Category: Biochemistry Authors: Tabujew I, Heidari M, Freidel C, Helm M, Tebbe L, Wolfrum U, Nagel-Wolfrum K, Koynov K, Biehl P, Schacher FH, Potestio R, Peneva K Tags: Biomacromolecules Source Type: research

Engineering the binding kinetics of synthetic polymer nanoparticles for siRNA delivery.
Abstract The affinity of a synthetic polymer nanoparticle (NP) to a target biomacromolecule is determined by the association and dissociation rate constants (kon, koff) of the interaction. The individual rates and their sensitivity to local environmental influences are important factors for the on demand capture and release a target biomacromolecule. Positively charged NPs for siRNA delivery is a case in point. The knockdown efficacy of siRNA can be strongly influenced by the binding kinetics to the NP. Here, we show that kon and koff of siRNA to NPs can be individually engineered by tuning the chemical structure ...
Source: Biomacromolecules - September 12, 2019 Category: Biochemistry Authors: Koide H, Fukuta T, Okishima A, Ariizumi S, Kiyokawa C, Tsuchida H, Nakamoto M, Yoshimatsu K, Ando H, Dewa T, Asai T, Oku N, Hoshino Y, Shea KJ Tags: Biomacromolecules Source Type: research

Polymeric Carriers for Nucleic Acid Delivery: Current Designs and Future Directions.
Abstract Within the last two decades a series of novel therapeutic nucleic acids entered research and clinical evaluation. Their differences both in biophysical properties as well as in mode and site of biological action provide polymer-based carriers with new delivery challenges. Recent tailor-made designs of polymeric carriers are reviewed that were optimized for nucleic acid cargos such as plasmid DNA, siRNA and micro RNA, messenger RNA or genome-modifying nucleic acids. The specific requirements for the various therapeutic cargos are discussed. Future directions include dynamic bioresponsive polymers as compon...
Source: Biomacromolecules - September 8, 2019 Category: Biochemistry Authors: Peng L, Wagner E Tags: Biomacromolecules Source Type: research

gH625 cell-penetrating peptide promotes the endosomal escape of nanovectorized siRNA in a triple negative breast cancer cell line.
Abstract The use of small interfering RNA (siRNA) to regulate oncogenes appears as a promising strategy in the context of cancer therapy, especially if they are vectorized by a smart delivery system. In the present study, we investigated the cellular trafficking of a siRNA nanovector (called CS-MSN) functionalized with the cell-penetrating peptides (CPP) gH625 in a triple negative breast cancer model. With complementary techniques, we showed that siRNA nanovectors were internalized by both clathrin- and caveolae-mediated endocytosis. The presence of gH625 at the surface of the siRNA nanovector did not modify the e...
Source: Biomacromolecules - July 14, 2019 Category: Biochemistry Authors: Ben Djemaa S, Herve-Aubert K, Lajoie L, Falanga A, Galdiero S, Nedellec S, Soucé M, Munnier E, Chourpa I, David S, Allard-Vannier E Tags: Biomacromolecules Source Type: research

Pyruvate responsiveness based on α-oxohydrazone formation for intracellular siRNA release from polyion complex (PIC)-based carriers.
This study provides the rationale for a smart design of pyruvate-responsive materials in the cell, based on α-oxohydrazone formation. PMID: 31091092 [PubMed - as supplied by publisher]
Source: Biomacromolecules - May 14, 2019 Category: Biochemistry Authors: Takemoto H, Wang CL, Nomoto T, Matsui M, Tomoda K, Nishiyama N Tags: Biomacromolecules Source Type: research

A Kinetic Model of Oligonucleotide-Brush Interactions for the Rational Design of Gene Delivery Vectors.
Abstract Polymer brushes are attractive candidates for the design of gene delivery vectors as they allow the systematic study of the impact of structural (type, size and shape of nanomaterials core) and physico-chemical parameters (cationic monomer chemistry, brush thickness and grafting density) on transfection efficiency. However, relatively little is known of their interactions of oligonucleotides. To study such interactions, we use surface plasmon resonance and developed a kinetic model of brush binding and infiltration. We identify the striking impact that brush grafting density and thickness have on oligonuc...
Source: Biomacromolecules - April 23, 2019 Category: Biochemistry Authors: Qu F, Li D, Ma X, Chen F, Gautrot J Tags: Biomacromolecules 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

Tumor Chemosensitization through Oncogene Knockdown Mediated by Unique α-Tocopherylated Cationic Geminis.
Abstract Herein, siRNA transfection efficiency of a unique set of α-tocopherylated gemini lipids has been established in vitro and in vivo. High efficacy of oncogene silencing achieved using the biomacromolecular assembly, formed from siRNA complexes of co-liposomes containing an α-tocopherylated gemini lipid, has been utilized for tumor regression via chemosensitization. Delivery studies with the gemini bearing hydroxyethyl headgroup with octamethylene spacer (TH8S) pointed to a higher siRNA transfection efficacy than its analog without hydroxyethyl group (T8S). Owing to p53 upregulation, transfected cells show...
Source: Biomacromolecules - March 24, 2019 Category: Biochemistry Authors: Kamra M, Maiti B, Dixit A, Karande AA, Bhattacharya S Tags: Biomacromolecules Source Type: research

Insights into siRNA transfection in suspension: Efficient gene silencing in human mesenchymal stem cells encapsulated in hyaluronic acid hydrogel.
Abstract Small interfering RNAs (siRNAs) are powerful tools for post-transcriptional gene silencing which offers enormous opportunities for tissue engineering applications. However, poor serum stability, inefficient intracellular delivery, and inevitable toxicity of transfection reagents are the key barriers for their clinical translation. Thus innovative strategies that allow safe and efficient intracellular delivery of the nucleic acid drugs at the desired site is urgently needed for a smooth clinical translation of therapeutically appealing siRNA-based technology. In this regard, we have developed an innovative...
Source: Biomacromolecules - January 14, 2019 Category: Biochemistry Authors: Paidikondala M, Nawale GN, Varghese OP Tags: Biomacromolecules Source Type: research

ATP-responsive low-molecular-weight polyethylenimine-based supramolecular assembly via host-guest interaction for gene delivery.
Abstract In this work, we report on an ATP-responsive low-molecular-weight polyethylenimine (LMW-PEI)-based supramolecular assembly. It formed via host-guest interaction between PEI (MW=1.8 kDa)-α-cyclodextrin (α-CD) conjugates and PEI1.8k-phenylboronic acid (PBA) conjugates. The host-guest interaction between PEI1.8k-α-CD and PEI1.8k-PBA was confirmed by the 2D-NOESY chromatogram experiment and competition test. The ATP-responsive property of the supramolecular assembly was evaluated by a series of ATP-triggered degradation and siRNA release studies in terms of fluorescence resonance energy transfer, agarose g...
Source: Biomacromolecules - December 5, 2018 Category: Biochemistry Authors: Jiang C, Qi Z, Jia H, Huang Y, Wang Y, Zhang W, Wu Z, Yang H, Liu J Tags: Biomacromolecules Source Type: research

Additive polyplexes to undertake siRNA therapy against CDC20 and survivin in breast cancer cells.
Abstract Small interfering RNA (siRNA) delivered to silence overexpressed genes associated with malignancies is a promising targeted therapy to decrease the uncontrolled growth of malignant cells. To create potent delivery agents for siRNA, here we formulated additive polyplexes of siRNA using linoleic acid-substituted polyethylenimine and additive polymers (hyaluronic acid, polyacrylic acid, dextran sulfate and methyl cellulose), and characterized their physicochemical properties and effectiveness. Incorporating polyanionic polymer along with anionic siRNA in polyplexes was found to decrease the ζ-potential of p...
Source: Biomacromolecules - September 17, 2018 Category: Biochemistry Authors: Parmar MB, K C RB, Löbenberg R, Uludag H Tags: Biomacromolecules Source Type: research