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A fluorinated peptide with high serum- and lipid-tolerence for the delivery of siRNA drugs to treat obesity and metabolic dysfunction
Biomaterials. 2022 Apr 28;285:121541. doi: 10.1016/j.biomaterials.2022.121541. Online ahead of print.ABSTRACTObesity is the major risk factor for metabolic diseases such as fatty liver, hyperlipidemia and insulin resistance. Beige fat has been recognized as a therapeutic target considering its great potential to burn energy. Since the evolutionary discovery of RNA interference and its utilization for gene knockdown in mammalian cells, a remarkable progress has been achieved in siRNA-based therapeutics. However, efficient delivery of siRNA into adipose tissues or differentiated adipocytes is challenging due to high lipid co...
Source: Biomaterials - May 9, 2022 Category: Materials Science Authors: Jin Qiu Qianqian Fan Sainan Xu Dongmei Wang Juntong Chen Sainan Wang Tianhui Hu Xinran Ma Yiyun Cheng Lingyan Xu Source Type: research

Versatile fully biodegradable dendritic nanotherapeutics
Biomaterials. 2022 Jan 3;281:121356. doi: 10.1016/j.biomaterials.2021.121356. Online ahead of print.ABSTRACTThe repeated administration of non-degradable dendrimers can lead to toxicity due to their bioaccumulation. Furthermore, in drug delivery applications, carrier stability can result in low biological performance due to insufficient intracellular cargo release. A novel family of versatile, biosafe, water-soluble, and fully biodegradable PEG-dendritic nanosystems is proposed, which overcomes the limitations of the most used dendrimers. Their novelty relies on the full and adjustable degradability thanks to the presence ...
Source: Biomaterials - January 15, 2022 Category: Materials Science Authors: Victoria Leiro Ana Patr ícia Spencer Nat ália Magalhães Ana Paula P êgo Source Type: research

Engineering multifunctional bioactive citric acid-based nanovectors for intrinsical targeted tumor imaging and specific siRNA gene delivery in vitro/in vivo.
Abstract Targeted tumor imaging and efficient specific gene delivery in vivo has been one of the main challenges in gene-based cancer diagnosis and therapy. Herein, we engineered a citric acid-based polymer with intrinsical photoluminescence and gene loading capacity to achieve targeted delivery of siRNA and tumor imaging in vitro and in vivo. The multifunctional platform was formed from the self-assembling of poly (citric acid)-polymine conjugated with folic acid and rhodamine B (PPFR). PPFR showed stable photoluminescent ability and could effectively bind and protect the siRNA against RNase degradation. PPFR als...
Source: Biomaterials - February 2, 2019 Category: Materials Science Authors: Wang M, Guo Y, Xue Y, Niu W, Chen M, Ma PX, Lei B Tags: Biomaterials Source Type: research

Ultrasound assisted gene and photodynamic synergistic therapy with multifunctional FOXA1-siRNA loaded porphyrin microbubbles for enhancing therapeutic efficacy for breast cancer.
Abstract To improve the non-invasive therapeutic efficacy for ER positive breast cancer (ER+ BC), we fabricated a multifunctional FOXA1 loaded porphyrin microbubble to combine photodynamic therapy (PDT) and gene therapy of FOXA1 knockdown (KD) with ultrasound targeted microbubble destruction (UTMD) technology under the guidance of contrast enhanced ultrasound (CEUS). Cationic porphyrin microbubbles (CpMBs) were firstly fabricated from a porphyrin grafted lipid with two cationic amino groups (PGL-NH2) and fluorocarbon inert gas of C3F8. Porphyrin group in the CpMBs monolayer could be used as a photosensitizer for ...
Source: Biomaterials - May 3, 2018 Category: Materials Science Authors: Zhao R, Liang X, Zhao B, Chen M, Liu R, Sun S, Yue X, Wang S Tags: Biomaterials Source Type: research

Gold-nanorods-siRNA nanoplex for improved photothermal therapy by gene silencing.
Abstract Nanomaterials-mediated photothermal therapy (PTT) often suffers from the fundamental cellular defense mechanism of heat shock response which leads to therapeutic resistance of cancer cells and reduces the therapeutic efficacy. Herein, a gold nanorods (GNRs)-siRNA platform with gene silencing capability is produced to improve the PTT efficiency. After surface modification, the GNRs show the ability to deliver siRNA oligos targeting BAG3 which is an efficient gene to block the heat-shock response. The synthesized GNRs-siRNA nanoplex exhibits excellent ability in the delivery of siRNA into cancer cells with ...
Source: Biomaterials - November 19, 2015 Category: Materials Science Authors: Wang BK, Yu XF, Wang JH, Li ZB, Li PH, Wang H, Song L, Chu PK, Li C Tags: Biomaterials Source Type: research

Regulation of vascular smooth muscle cell autophagy by DNA nanotube-conjugated mTOR siRNA.
Abstract The efficient delivery of short interfering RNA (siRNA) is an enormous challenge in the field of gene therapy. Herein, we report a delivery nanosystem based on programmed DNA self-assembly mammalian target of rapamycin (mTOR) siRNA-loaded DNA nanotubes (DNA-NTs). We demonstrate that these siRNA-DNA-NTs can be effectively transfected into pulmonary arterial smooth muscle cells (PASMCs) via endocytosis; and that the loaded mTOR siRNA can induce obvious autophagy and inhibit cell growth under both normal and hypoxic conditions. Moreover, we found that mTOR siRNA can control the autophagy and proliferation of...
Source: Biomaterials - July 16, 2015 Category: Materials Science Authors: You Z, Qian H, Wang C, He B, Yan J, Mao C, Wang G Tags: Biomaterials Source Type: research

Plasma hydrogenated cationic detonation nanodiamonds efficiently deliver to human cells in culture functional siRNA targeting the Ewing sarcoma junction oncogene.
Abstract The expression of a defective gene can lead to major cell dysfunctions among which cell proliferation and tumor formation. One promising therapeutic strategy consists in silencing the defective gene using small interfering RNA (siRNA). In previous publications we showed that diamond nanocrystals (ND) of primary size 35 nm, rendered cationic by polyethyleneimine-coating, can efficiently deliver siRNA into cell, which further block the expression of EWS/FLI-1 oncogene in a Ewing sarcoma disease model. However, a therapeutic application of such nanodiamonds requires their elimination by the organism, partic...
Source: Biomaterials - February 13, 2015 Category: Materials Science Authors: Bertrand JR, Pioche-Durieu C, Ayala J, Petit T, Girard HA, Malvy CP, Le Cam E, Treussart F, Arnault JC Tags: Biomaterials Source Type: research

Tumor targeting RGD conjugated bio-reducible polymer for VEGF siRNA expressing plasmid delivery.
Abstract Targeted delivery of therapeutic genes to the tumor site is critical for successful and safe cancer gene therapy. The arginine grafted bio-reducible poly (cystamine bisacrylamide-diaminohexane, CBA-DAH) polymer (ABP) conjugated poly (amido amine) (PAMAM), PAM-ABP (PA) was designed previously as an efficient gene delivery carrier. To achieve high efficacy in cancer selective delivery, we developed the tumor targeting bio-reducible polymer, PA-PEG1k-RGD, by conjugating cyclic RGDfC (RGD) peptides, which bind αvβ3/5 integrins, to the PAM-ABP using polyethylene glycol (PEG, 1 kDa) as a spacer. Physical cha...
Source: Biomaterials - May 31, 2014 Category: Materials Science Authors: Kim HA, Nam K, Kim SW Tags: Biomaterials Source Type: research

Molecular modeling of polynucleotide complexes.
Abstract Delivery of polynucleotides into patient cells is a promising strategy for treatment of genetic disorders. Gene therapy aims to either synthesize desired proteins (DNA delivery) or suppress expression of endogenous genes (siRNA delivery). Carriers constitute an important part of gene therapeutics due to limitations arising from the pharmacokinetics of polynucleotides. Non-viral carriers such as polymers and lipids protect polynucleotides from intra and extracellular threats and facilitate formation of cell-permeable nanoparticles through shielding and/or bridging multiple polynucleotide molecules. Format...
Source: Biomaterials - May 21, 2014 Category: Materials Science Authors: Meneksedag-Erol D, Tang T, Uludağ H Tags: Biomaterials Source Type: research

Inhibition of hepatocellular carcinoma growth using immunoliposomes for co-delivery of adriamycin and ribonucleotide reductase M2 siRNA.
Abstract The chemotherapy combined with gene therapy has received great attention. We developed targeted LPD (liposome-polycation-DNA complex) conjugated with anti-EGFR (epidermal growth factor receptor) Fab' co-delivering adriamycin (ADR) and ribonucleotide reductase M2 (RRM2) siRNA (ADR-RRM2-TLPD), to achieve combined therapeutic effects in human hepatocellular carcinoma (HCC) overexpressing EGFR. The antitumor activity and mechanisms of ADR-RRM2-TLPD were investigated. The results showed that RRM2 expression was higher in HCC than in non-HCC tissue, and RRM2 siRNA inhibited HCC cell proliferation, suggesting th...
Source: Biomaterials - September 20, 2013 Category: Materials Science Authors: Gao J, Chen H, Yu Y, Song J, Song H, Su X, Li W, Tong X, Qian W, Wang H, Dai J, Guo Y Tags: Biomaterials Source Type: research

Combinational delivery of c-myc siRNA and nucleoside analogs in a single, synthetic nanocarrier for targeted cancer therapy.
In this study, we developed a Lipid/Calcium/Phosphate (LCP) nanoparticle that combines chemotherapy with gene therapy. By encapsulating a chemodrug, gemcitabine monophosphate (GMP), and siRNA specific to the undruggable cMyc oncogene (cMyc siRNA) into a single nano-sized vesicle and systemically administering them to nude mice, we achieved potent anti-tumor activity in both subcutaneous and orthotopic models of NSCLC. The improvements in therapeutic response over either cMyc siRNA or GMP therapy alone, were demonstrated by the ability to effectively induce the apoptosis of tumor cells and the significant reduction of proli...
Source: Biomaterials - August 8, 2013 Category: Materials Science Authors: Zhang Y, Peng L, Mumper RJ, Huang L Tags: Biomaterials Source Type: research

A review of the current status of siRNA nanomedicines in the treatment of cancer.
Abstract RNA interference currently offers new opportunities for gene therapy by the specific extinction of targeted gene(s) in cancer diseases. However, the main challenge for nucleic acid delivery still remains its efficacy through intravenous administration. Over the last decade, many delivery systems have been developed and optimized to encapsulate siRNA and to specifically promote their delivery into tumor cells and improve their pharmacokinetics for anti-cancer purposes. This review aims to sum up the potential targets in numerous pathways and the properties of recently optimized siRNA synthetic nanomedicine...
Source: Biomaterials - May 30, 2013 Category: Materials Science Authors: Resnier P, Montier T, Mathieu V, Benoit JP, Passirani C Tags: Biomaterials Source Type: research