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Targeting Rab26 to Conquer Cisplatin-Resistant Lung Cancer with Self-Assembled DNA Nanomaterials
In this study, we developed a nanosystem based on programmed DNA self-assembly of Rab26 siRNA-loaded nanoparticles (siRNP). We demonstrated that siRNP could be effectively transfected into cisplatin-resistant A549 (A549/DDP) cells. These siRab26-carrying nanoparticles induced apoptosis and inhibited the disruption of autophagy. The combination therapy of siRab26 knockdown with cisplatin could improve the antitumor therapy compared with a single one in vitro. In nude mice, siRNP enhanced the chemosensitivity of cisplatin-resistant cells and inhibited tumor xenograft development. These outcomes suggest that siRNP is an effec...
Source: Biomacromolecules - April 3, 2023 Category: Biochemistry Authors: Beinuo Wang Ruijie Zhang Yao Wang Hang Qian Di Wu Binfeng He Hu Liao 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

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

Small Delivery Vehicles of siRNA for Enhanced Cancer Targeting.
Abstract Small interfering RNA (siRNA) drugs have been considered to treat various diseases in major organs. However, siRNA drugs developed for cancer therapy are hindered from proceeding to clinics. To date, various delivery formulations have been developed from cationic lipids, polymers, and/or inorganic nanoparticles for systemic siRNA delivery to solid tumors. Most of these delivery vehicles do not generate small particle sizes and pharmacokinetics required for accumulation in target cancer cells, compared with clinically tested anticancer drug-loaded polymeric micelles. This review describes the significance ...
Source: Biomacromolecules - June 4, 2018 Category: Biochemistry Authors: Kim HJ, Yi Y, Kim A, Miyata K Tags: Biomacromolecules Source Type: research

Cyclam-Modified PEI for Combined VEGF siRNA Silencing and CXCR4 Inhibition To Treat Metastatic Breast Cancer.
Abstract Chemokine receptor CXCR4 plays an important role in cancer cell invasion and metastasis. Recent findings suggest that anti-VEGF therapies upregulate CXCR4 expression, which contributes to resistance to antiangiogenic therapies. Here, we report the development of novel derivatives of polyethylenimine (PEI) that effectively inhibit CXCR4 while delivering anti-VEGF siRNA. PEI was alkylated with different amounts of a CXCR4-binding cyclam derivative to prepare PEI-C. Modification with the cyclam derivatives resulted in a considerable decrease in cytotoxicity when compared with unmodified PEI. All the PEI-C sh...
Source: Biomacromolecules - January 19, 2018 Category: Biochemistry Authors: Zhou Y, Yu F, Zhang F, Chen G, Wang K, Sun M, Li J, Oupický D Tags: Biomacromolecules Source Type: research

A biodegradable stearylated peptide with internal disulfide bonds for efficient delivery of siRNA in vitro and in vivo.
In this study, a stearyl-peptide (SHR) was synthesized using arginine, histidine, cysteine and stearyl moiety. Further, the stearyl-peptides were cross linked by disulfide bonds to obtain cross-linked polypeptides (SHRss) with different molecular weight (SHRss1, SHRss2, SHRss3, SHRss4). The SHRss could effectively condense small interfering RNA (siRNA) into polyplexes with a hydrodynamic size of 100-300 nm and zeta potential of 20-40 mV. Flow cytometry and confocal laser scanning microscope studies revealed high cellular uptake and rapid dissociation behavior of SHRss2/siRNA complexes. Long-lasting high concentration of si...
Source: Biomacromolecules - February 16, 2015 Category: Biochemistry Authors: Tai Z, Wang X, Tian J, Gao Y, Zhang L, Yao C, Wu X, Zhang W, Zhu Q, Gao S Tags: Biomacromolecules Source Type: research

Impact of the Structure of Biocompatible Aliphatic Polycarbonates on siRNA Transfection Ability.
Abstract RNAi therapeutics are promising therapeutic tools that have sparked the interest of many researchers. In an effort to provide a safe alternative to PEI, we have designed a series of new guanidinium and/or morpholino functionalized biocompatible and biodegradable polycarbonate vectors. The impact of different functions (morpholino-, guanidinium-, hydrophobic groups), of the architecture (linear homopolymer to dumbbell-shape) and of the molecular weight of these copolymers on their capacity to form polyplexes and to decrease the expression of two epigenetic regulators of gene expression, HDAC7 and HDAC5 was...
Source: Biomacromolecules - January 20, 2015 Category: Biochemistry Authors: Frère A, Kawalec M, Tempelaar S, Peixoto P, Hendrick E, Peulen O, Evrard B, Dubois P, Mespouille L, Mottet D, Piel G Tags: Biomacromolecules Source Type: research