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Advantages and Challenges in nanomedicines for chronic liver diseases: a hepatologist's perspectives.
Abstract Chronic liver disease (CLD) is responsible for significant morbidity and mortality worldwide. CLD patients are at a high risk of developing progressive liver fibrosis, cirrhosis, hepatocellular carcinoma (HCC), and subsequent liver failure. To date, there is no specific and effective therapies exist for patients with various forms of CLD. The application of nanotechnology has emerged as a rapidly developing area of interest for the safe and target-specific delivery of poorly aqueous soluble hepatoprotective agents and nucleic acids (siRNA/miRNAs) in CLD. The nanoparticle combination improves bioavailabili...
Source: European Journal of Pharmacology - December 21, 2020 Category: Drugs & Pharmacology Authors: Ezhilarasan D Tags: Eur J Pharmacol Source Type: research

Activatable MRI-monitoring gene delivery for the theranostic of renal carcinoma
In this study, we constructed a PEG-MnO2-OPN siRNA nanocomplex via a modular streptavidin bridge for the theranostic treatment of renal carcinoma in vitro and in vivo. This strategy of utilizing PEG-MnO2 nanosheets for OPN siRNA delivery showed effective tumor growth inhibition of 786-O tumor-bearing mice, and such a process could be monitored by the activated T1-weight MRI, illustrating the promising potential of PEG-MnO2 nanosheets for the fabrication of an MRI-based theranostic system.
Source: Colloids and Surfaces B: Biointerfaces - December 8, 2019 Category: Biochemistry Source Type: research

Enhanced anticancer effect of doxorubicin by TPGS-coated liposomes with Bcl-2 siRNA-corona for dual suppression of drug resistance
In conclusion, TPGS-coated cationic liposomes with Bcl-2 siRNA corona had the capacity to inhibit MDR dual-pathways and subsequently improved the anti-tumor activity of the chemotherapeutic agent co-delivered to a level that cannot be achieved by inhibiting a MDR single way.Graphical abstract
Source: Asian Journal of Pharmaceutical Sciences - November 13, 2019 Category: Drugs & Pharmacology Source Type: research

Development of siRNA Delivery Targeting the Tumor Microenvironment with a New Functional Device.
In conclusion, I succeeded in developing a new therapy based on regulation of the tumor microenvironment. PMID: 31685731 [PubMed - in process]
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - November 8, 2019 Category: Drugs & Pharmacology Authors: Sakurai Y Tags: Yakugaku Zasshi Source Type: research

Activatable MRI-monitoring gene delivery for the theranostic of renal carcinoma.
In this study, we constructed a PEG-MnO2-OPN siRNA nanocomplex via a modular streptavidin bridge for the theranostic treatment of renal carcinoma in vitro and in vivo. This strategy of utilizing PEG-MnO2 nanosheets for OPN siRNA delivery showed effective tumor growth inhibition of 786-O tumor-bearing mice, and such a process could be monitored by the activated T1-weight MRI, illustrating the promising potential of PEG-MnO2 nanosheets for the fabrication of an MRI-based theranostic system. PMID: 31734089 [PubMed - as supplied by publisher]
Source: Colloids and Surfaces - November 7, 2019 Category: Biotechnology Authors: Shi M, Wang S, Zheng S, Hou P, Dong L, He M, Wu C, Zhang X, Zuo F, Xu K, Li J Tags: Colloids Surf B Biointerfaces Source Type: research

Glycyrrhetinic acid-modified graphene oxide mediated siRNA delivery for enhanced liver-cancer targeting therapy.
Abstract Graphene oxide (GO) has attracted huge attention in biomedical field in recent years. However, limited attempts have been invested in utilizing GO on active targeted delivery for gene therapy in liver cancer treatments. Glycyrrhetinic acid (GA) has been reported to be widely used as a targeting ligand to functionalize nanomaterials to treat hepatocellular carcinoma. In this article, GA is employed as a liver targeting ligand to construct GA, polyethylene glycol (PEG), polyamidoamine dendrimer (Dendrimer) and nano-graphene oxide (NGO) conjugate (GA-PEG-NGO-Dendrimer, GPND) for siRNA delivery for the first ...
Source: European Journal of Pharmaceutical Sciences - August 21, 2019 Category: Drugs & Pharmacology Authors: Qu Y, Sun F, He F, Yu C, Lv J, Zhang Q, Liang D, Yu C, Wang J, Zhang X, Xu A, Wu J Tags: Eur J Pharm Sci Source Type: research

Covalent conjugates of granulin-epithelial precursor-siRNA with arginine-rich peptide for improved stability and intracellular delivery in hepatoma cells
Conclusion: These results provide insights into the importance of chemical modification of unstable genetic therapeutics for HCC treatment. Conjugation of PEGylated GEP siRNA with ARP may be a potential HCC therapeutic agent.
Source: Molecular and Cellular Toxicology - June 27, 2019 Category: Cytology Source Type: research

Polyamidoamine dendrimers-based nanomedicine for combination therapy with siRNA and chemotherapeutics to overcome multidrug resistance.
Abstract Multidrug resistance (MDR) significantly decreases the therapeutic efficiency of anti-cancer drugs. Its reversal could serve as a potential method to restore the chemotherapeutic efficiency. Downregulation of MDR-related proteins with a small interfering RNA (siRNA) is a promising way to reverse the MDR effect. Additionally, delivery of small molecule therapeutics simultaneously with siRNA can enhance the efficiency of chemotherapy by dual action in MDR cell lines. Here, we conjugated the dendrimer, generation 4 polyamidoamine (G4 PAMAM), with a polyethylene glycol (PEG)-phospholipid copolymer. The amphip...
Source: European Journal of Pharmaceutics and Biopharmaceutics - January 8, 2019 Category: Drugs & Pharmacology Authors: Pan J, Palmerston Mendes L, Yao M, Filipczak N, Garai S, Thakur GA, Sarisozen C, Torchilin VP Tags: Eur J Pharm Biopharm 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

Iron‐Oxide‐Based Nanovector for Tumor Targeted siRNA Delivery in an Orthotopic Hepatocellular Carcinoma Xenograft Mouse Model
Hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide. Small interfering RNA (siRNA) holds promise as a new class of therapeutics for HCC, as it can achieve sequence‐specific gene knockdown with low cytotoxicity. However, the main challenge in the clinical application of siRNA lies in the lack of effective delivery approaches that need to be highly specific and thus incur low or no systemic toxicity. Here, a nonviral nanoparticle‐based gene carrier is presented that can specifically deliver siRNA to HCC. The nanovector (NP‐siRNA‐GPC3 Ab) is made of an iron oxide core coated with chitosan‐polyet...
Source: Small - December 1, 2015 Category: Nanotechnology Authors: Kui Wang, Forrest M. Kievit, Jonathan G. Sham, Mike Jeon, Zachary R. Stephen, Arvind Bakthavatsalam, James O. Park, Miqin Zhang Tags: Full Paper Source Type: research

Abstract 5400: A novel combinatorial therapy for hepatocellular carcinoma (HCC)
The incidence of hepatocellular carcinoma (HCC) is rising in the US with parallel increase in mortality rate. Lack of effective therapy for advanced HCC mandates development of novel targeted therapies to counteract this fatal malady. Astrocyte elevated gene-1 (AEG-1), also known as metadherin (MTDH) and LYRIC, plays a pivotal role in hepatocarcinogenesis and serves as an ideal target for anti-HCC therapy. AEG-1 interacts with retinoid X receptor (RXR) and inhibits retinoic acid-induced gene expression and cell death. Retinoic acid has been evaluated for HCC treatment without promising result. Overexpression of AEG-1 might...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Srivastava, J., Rajasekaran, D., Siddiq, A., Gredler, R., Robertson, C. L., Akiel, M. A., Shen, X.-N., Ebeid, K. A. N., Salem, A. K., Fisher, P. B., Sarkar, D. Tags: Experimental and Molecular Therapeutics Source Type: research

Targeted gene silencing using a follicle-stimulating hormone peptide-conjugated nanoparticle system improves its specificity and efficacy in ovarian clear cell carcinoma in vitro
Conclusions: This study indicated that a FSHR-mediated delivery system could mediate the highly selective delivery of siRNA into ovarian cancer cells and that silencing gro-alpha expression could be a potential choice for ovarian cancer treatment.
Source: Journal of Ovarian Research - November 20, 2013 Category: Cancer & Oncology Authors: Shanshan HongXiaoyan ZhangJun ChenJiabing ZhouYufang ZhengCongjian Xu Source Type: research

Cationic lipid nanoparticles for therapeutic delivery of siRNA and miRNA to murine liver tumor
In this study, LNP-DP1 –a cationic lipid nanoparticle formulation –is reported as a vehicle to restore deregulated gene expression in hepatic carcinoma cells by siRNA and miRNA delivery using a mouse model. Further expansions to this study may enable transition to clinical trials of this system.Graphical Abstract: The schematic representation of mi-/si-RNA encapsulated by PEG modified LNP-DP1 which is mainly composed of EggPC, cholesterol and cationic lipid DODMA. The LNP-DP1 (red particles) can be specifically and efficiently taken up by hepatocytes and tumor cells (blue nuclei and green cell outline) after delivery t...
Source: Nanomedicine : Nanotechnology, Biology, and Medicine - June 3, 2013 Category: Nanotechnology Authors: Shu-hao Hsu, Bo Yu, Xinmei Wang, Yuanzhi Lu, Carl R. Schmidt, Robert J. Lee, L. James Lee, Samson T. Jacob, Kalpana Ghoshal Tags: Genetics, Gene Delivery, HEP-CC, Micro-RNA Delivery, Cationic Lipid NPs Source Type: research