A novel injectable thermoresponsive and cytocompatible gel of poly(N-isopropylacrylamide) with layered double hydroxides facilitates siRNA delivery into chondrocytes in 3D culture

Yang, Hsiao-yin; Ee, Renz J. van; Timmer, K.; Craenmehr, E.G.M.; Huang, Julie H.; Öner, FC; Dhert, Wouter J.A.; Kragten, Angela; Willems, Nicole; Grinwis, Guy C. M.; Tryfonidou, Marianna A.; Papen-Botterhuis, N.E.; Creemers, Laura B.

doi:10.1016/j.actbio.2015.05.018

Cited by 46 publications

(30 citation statements)

References 82 publications

(86 reference statements)

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“…These classes of RNAs silence the expression of specific genes by complementary binding and degradation of their mRNA. Several studies have incorporated NF-κB siRNA in nanoparticles fabricated from cell-penetrating peptide [71] and injectable thermoresponsive hydrogel for on-demand release [72].…”

Section: Disease-modifying Treatmentsmentioning

confidence: 99%

Inflammation-Modulating Hydrogels for Osteoarthritis Cartilage Tissue Engineering

Koh

Jin

Kim

et al. 2020

Cells

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Osteoarthritis (OA) is the most common form of the joint disease associated with age, obesity, and traumatic injury. It is a disabling degenerative disease that affects synovial joints and leads to cartilage deterioration. Despite the prevalence of this disease, the understanding of OA pathophysiology is still incomplete. However, the onset and progression of OA are heavily associated with the inflammation of the joint. Therefore, studies on OA treatment have sought to intra-articularly deliver anti-inflammatory drugs, proteins, genes, or cells to locally control inflammation in OA joints. These therapeutics have been delivered alone or increasingly, in delivery vehicles for sustained release. The use of hydrogels in OA treatment can extend beyond the delivery of anti-inflammatory components to have inherent immunomodulatory function via regulating immune cell polarization and activity. Currently, such immunomodulatory biomaterials are being developed for other applications, which can be translated into OA therapy. Moreover, anabolic and proliferative levels of OA chondrocytes are low, except initially, when chondrocytes temporarily increase anabolism and proliferation in response to structural changes in their extracellular environment. Therefore, treatments need to restore matrix protein synthesis and proliferation to healthy levels to reverse OA-induced damage. In conjugation with injectable and/or adhesive hydrogels that promote cartilage tissue regeneration, immunomodulatory tissue engineering solutions will have robust potential in OA treatment. This review describes the disease, its current and future immunomodulatory therapies as well as cartilage-regenerative injectable and adhesive hydrogels.

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Section: Disease-modifying Treatmentsmentioning

confidence: 99%

Inflammation-Modulating Hydrogels for Osteoarthritis Cartilage Tissue Engineering

Koh

Jin

Kim

et al. 2020

Cells

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“…Among these, nanoparticles, especially the magnetic iron oxide (Fe3O4) nanoparticles seem to be a promising tool for site specific delivery [14,15], based on the fact that they will release the anticancer drug on tumor cells owing to the enhanced permeability and retention (EPR) effect [16,17] and passive drug targeting. Furthermore, recently layered double hydroxide (LDH) nanoparticles have been proven effective for site-specific delivery of anticancer drugs to tumor and reduce its side effects, due to their inherent properties such as high biocompatibility [18], low cytotoxicity [19], the ability to accommodate various biologically important molecules including genes and drugs [20][21][22], and the partial dissolution of LDH layers in endosome that not only stops the passive control release of drugs, but also buffers the excess protons, which helps the drugs to escape from endosome, improves the viability of drugs in cytoplasm, and enhances the delivery efficacy [23]. MgAl-LDH, specifically, is reported to be more efficient than other LDHs because of its weak alkalinity and the pH-sensitive ability of slow degradation in an acidic environment like endosomes (pH 5.0-6.0) or lysosomes (pH 3.5-4.5) [24,25], and the yielded ions such as Mg 2+ , Al 3+ , or NO3…”

Section: Introductionmentioning

confidence: 99%

Synthesis and in vitro evaluation of pH-sensitive magnetic nanocomposites as methotrexate delivery system for targeted cancer therapy

Deng

Jiang

et al. 2017

Materials Science and Engineering: C

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This study focuses on the synthesis and in vitro evaluation of magnetic nanocomposites (FeO@LDH) as methotrexate (MTX) delivery system for targeted anticancer therapy. In which, the FeO nanoparticles acted as magnetically responsive carriers; the coating layer of layered double hydroxide (LDH) was used as a storehouse for MTX. The prepared FeO@LDH nanocomposites exhibited a suitable size, good stability and magnetic responsibility (M 36.66emu/g); MTX successfully intercalated into the LDH of FeO@LDH at an entrapment rate (%) of 91.78% (the drug loading was 18.36%) by host-guest exchange process. Moreover, the release studies in vitro showed that the drug delivery system (FeO@LDH-MTX) had excellent pH-sensitivity, 84.94% of MTX was released within 48h at pH3.5 via the co-effect of dissolution of LDH layer and ion-exchange. WST-1 assays in cancer cells (MCF-7 and HepG2) and normal cells (HUVEC) demonstrated that FeO@LDH-MTX exhibited high anticancer activity while low toxicity to normal cells, and also the FeO@LDH composites were practically non-toxic. Thus, our results revealed that FeO@LDH-MTX would be a competitive candidate for targeted delivery and sustained and controlled release of MTX.

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“…Lastly, the incorporation of RNAi nucleic acids may be either direct or with inclusion of nanoparticles ( Figure ). RNAi therapeutics have also been encapsulated along with cells, towards the fabrication of scaffolds to support 3D cellular migration and proliferation towards both regenerative medicine and tissue engineering . However, this review will focus on the design of hydrogels for local gene silencing without added cells and this section provides an overview of the various design components towards hydrogels for RNAi delivery.…”

Section: Design Considerations In Engineering Hydrogels For Rnai Delimentioning

confidence: 99%

Engineered Hydrogels for Local and Sustained Delivery of RNA‐Interference Therapies

Wang

Burdick

2016

Adv Healthcare Materials

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It has been nearly two decades since RNA-interference (RNAi) was first reported. While there are no approved clinical uses, several promising phase II and III clinical trials suggest the great promise of RNAi therapeutics. One challenge for RNAi therapies is the controlled localization and sustained presentation to target tissues, to both overcome systemic toxicity concerns and to enhance in vivo efficacy. One approach that is emerging to address these limitations is the entrapment of RNAi molecules within hydrogels for local and sustained release. In these systems, nucleic acids are either delivered as siRNA conjugates or within nanoparticles. A plethora of hydrogels has been implemented using these approaches, including both traditional hydrogels that have already been developed for other applications and new hydrogels developed specifically for RNAi delivery. These hydrogels have been applied to various applications in vivo, including cancer, bone regeneration, inflammation and cardiac repair. This review will examine the design and implementation of such hydrogel RNAi systems and will cover the most recent applications of these systems.

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A novel injectable thermoresponsive and cytocompatible gel of poly(N-isopropylacrylamide) with layered double hydroxides facilitates siRNA delivery into chondrocytes in 3D culture

Cited by 46 publications

References 82 publications

Inflammation-Modulating Hydrogels for Osteoarthritis Cartilage Tissue Engineering

Inflammation-Modulating Hydrogels for Osteoarthritis Cartilage Tissue Engineering

Synthesis and in vitro evaluation of pH-sensitive magnetic nanocomposites as methotrexate delivery system for targeted cancer therapy

Engineered Hydrogels for Local and Sustained Delivery of RNA‐Interference Therapies

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