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Stimuli ‐responsive nanoparticles for the codelivery of chemotherapeutic agents doxorubicin and siPD‐L1 to enhance the antitumor effect
In this study, a nanodelivery system was designed to incorporate doxorubicin (DOX) and programmed death ‐ligand 1 (PD‐L1) small interfering RNA (siRNA), that is, siPD‐L1. DOX and siPD‐L1 were formed from a stimuli‐responsive polymer with a poly‐L‐lysine–lipoic acid reduction‐sensitive core and a tumor extracellular pH‐stimulated shedding polyethylene glycol layer. The codelivery sy stem was stable under physiological pH conditions and demonstrated enhanced cellular uptake at the tumor site. Moreover, the combined treatment of DOX and siPD‐L1 exhibited improved antitumor effect in vitro and in vivo com...
Source: Journal of Biomedical Materials Research Part B: Applied Biomaterials - November 19, 2019 Category: Materials Science Authors: Ye ‐juan Zhou, Wen‐jun Wan, Yao Tong, Meng‐tian Chen, Dan‐dan Wang, Yu Wang, Ben‐gang You, Yang Liu, Xue‐nong Zhang Tags: ORIGINAL RESEARCH REPORT 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

Hepatocyte-Targeted Delivery of siRNA Polyplex with PEG-Modified Lactosylated Dendrimer/Cyclodextrin Conjugates for Transthyretin-Related Amyloidosis Therapy.
Abstract Targeted drug delivery system (DDS) is required for RNA interference (RNAi) therapy to increase the therapeutic effect and to reduce the adverse effect. Especially in transthyretin (TTR)-related amyloidosis, hepatocyte specific delivery is desired because TTR mainly expresses in hepatocyte. Herein, we report on a hepatocyte-specific small interfering RNA (siRNA) delivery system using polyethylene glycol (PEG)-modified lactosylated dendrimer (generation 3; G3) conjugates with α-cyclodextrin (PEG-LαCs (G3)) for TTR-related amyloidosis therapy, and investigated the in vitro and in vivo gene silencing effec...
Source: Biological and Pharmaceutical Bulletin - October 6, 2019 Category: Drugs & Pharmacology Authors: Hayashi Y, Higashi T, Motoyama K, Jono H, Ando Y, Onodera R, Arima H Tags: Biol Pharm Bull 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

Biodegradable Polyester of Poly (Ethylene glycol)-sebacic Acid as a Backbone for β-Cyclodextrin-polyrotaxane: A Promising Gene Silencing Vector.
CONCLUSION: The combinatory effect of various factors such as biodegradability, favourable complexation ability, near zero zeta potentials, good cytotoxicity properties of poly (ethylene glycol)-sebacic acid based β-Cyclodextrin-polyrotaxane makes it a potential gene delivery vector for therapeutic applications. PMID: 31393245 [PubMed - as supplied by publisher]
Source: Current Gene Therapy - August 6, 2019 Category: Genetics & Stem Cells Authors: Ghodke S, Mahajan P, Gupta K, Ver Avadhani C, Dandekar P, Jain R Tags: Curr Gene Ther Source Type: research

A Fit-for-Purpose Method for the Detection of Human Antibodies to Surface-Exposed Components of BMS-986263, a Lipid Nanoparticle-Based Drug Product Containing a siRNA Drug Substance
AbstractND-L02-s0201/BMS-986263 is a lipid nanoparticle (LNP) drug product containing a heat shock protein 47 (HSP47) –specific small interfering ribonucleic acid (siRNA) and being developed for the treatment of liver and idiopathic pulmonary fibrosis. To address immunogenicity-related issues, we developed a robust, fit-for-purpose (FFP) three-tier electrochemiluminescent (ECL) anti-drug antibody (ADA) assay for the detection of antibodies (Abs) generated to surface-exposed components of BMS-986263. The drug was coated directly on plates, and several Abs specific for polyethylene glycol (PEG) and other surface components...
Source: The AAPS Journal - July 21, 2019 Category: Drugs & Pharmacology 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

Design of a Novel PEGylated Liposomal Vector for Systemic Delivery of siRNA to Solid Tumors.
Abstract A small interfering RNA (siRNA) delivery system using dioleylphosphate-diethylenetriamine conjugate (DOP-DETA)-based liposomes (DL) was assessed for systemic delivery of siRNA to tumors. DL carrying siRNA capable of inducing efficient gene silencing with low doses of siRNA were modified with polyethylene glycol (PEG-DL/siRNA) for systemic injection of siRNA. The biodistribution of DL and siRNA in the PEG-DL/siRNA was studied by using radiolabeled DL and fluorescence-labeled siRNA, respectively. DL in the PEG-DL/siRNA showed a high retention in the plasma, accumulation in the tumor, and low accumulation in...
Source: Biological and Pharmaceutical Bulletin - June 4, 2019 Category: Drugs & Pharmacology Authors: Song F, Sakurai N, Okamoto A, Koide H, Oku N, Dewa T, Asai T Tags: Biol Pharm Bull Source Type: research

Efficient delivery of small interfering RNAs targeting particular mRNAs into pancreatic cancer cells inhibits invasiveness and metastasis of pancreatic tumors.
We report the use of small interfering RNAs (siRNAs) against ARHGEF4, CCDC88A, LAMTOR2, mTOR, NUP85, and WASF2 and folic acid (FA)-modified polyethylene glycol (PEG)-chitosan oligosaccharide lactate (COL) nanoparticles for targeting, imaging, delivery, gene silencing, and inhibition of invasiveness and metastasis in an orthotopic xenograft model. In vitro assays revealed that these siRNA-FA-PEG-COL nanoparticles were specifically inserted into pancreatic cancer cells compared to immortalized normal pancreatic epithelial cells and knocked down expression of the corresponding targets in pancreatic cancer cells. Cell motility...
Source: Oncotarget - May 15, 2019 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Engineered Extracellular Vesicles From Human Periodontal-Ligament Stem Cells Increase VEGF/VEGFR2 Expression During Bone Regeneration
Conclusion In conclusion our results evidenced that 3D-COL/hPDLSCs/PEI-EVs may be an efficacious strategy to induce bone regeneration and vascularization of bone defects, thanks to its capacity to increase the levels of VEGF. Ethics Statement The study was performed in accordance with the guidelines of the Helsinki Declaration (2013). The written approval for the human periodontal ligament collection performed in this study has been obtained from the Medical Ethics Committee at the Medical School, “G. d’Annunzio” University of Chieti–Pescara, Chieti, Italy (n°266/17.04.14, Principal in...
Source: Frontiers in Physiology - April 29, 2019 Category: Physiology Source Type: research

Localized RNA interference therapy to eliminate residual lung cancer after incomplete microwave ablation
ConclusionPEG ‐PEI‐EGFR‐siRNA nanocomposites may be a supplemental therapy strategy to treat residual lung cancer after incomplete MWA.
Source: Thoracic Cancer - April 23, 2019 Category: Cancer & Oncology Authors: Fei Cao, Chao Wan, Lin Xie, Han Qi, Lujun Shen, Shuanggang Chen, Ze Song, Weijun Fan Tags: ORIGINAL ARTICLE Source Type: research

Multifunctional drug carrier based on PEI derivatives loaded with small interfering RNA for therapy of liver cancer
Publication date: Available online 17 April 2019Source: International Journal of PharmaceuticsAuthor(s): Yarong Zhao, Robert J. Lee, Luotong Liu, Shiyan Dong, Jing Zhang, Yu Zhang, Yicheng Yao, Jiahui Lu, Qingfan Meng, Jing Xie, Lesheng TengAbstractGene therapy strategies for liver cancer have broad application prospects but still lack a stable and efficient delivery vehicle. To overcome this obstacle, we designed a multifunctional gene delivery vector, sTPssOLP, which was based on oleylamine (OA)-modified disulfide-containing polyethylenimine (PEI) and incorporated into lipids to prepare a lipid nanoparticle. sTPssOLP con...
Source: International Journal of Pharmaceutics - April 18, 2019 Category: Drugs & Pharmacology Source Type: research

In Vitro and In Vivo Co-delivery of siRNA and Doxorubicin by Folate-PEG-Appended Dendrimer/Glucuronylglucosyl- β-Cyclodextrin Conjugate
AbstractWe have previously reported the utility of folate-polyethylene glycol-appended dendrimer conjugate with glucuronylglucosyl- β-cyclodextrin (Fol-PEG-GUG-β-CDE) (generation 3) as a tumor-selective carrier for siRNA against polo-like kinase 1 (siPLK1)in vitro. In the present study, we evaluated the potential of Fol-PEG-GUG- β-CDE as a carrier for the low-molecular antitumor drug doxorubicin (DOX). Further, to fabricate advanced antitumor agents, we have prepared a ternary complex of Fol-PEG-GUG-β-CDE/DOX/siPLK1 and evaluated its antitumor activity bothin vitro andin vivo. Fol-PEG-GUG- β-CDE released DOX in an aci...
Source: The AAPS Journal - April 15, 2019 Category: Drugs & Pharmacology Source Type: research

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