Chemisorption Mechanism of DNA on Mg/Fe Layered Double Hydroxide Nanoparticles: Insights into Engineering Effective SiRNA Delivery Systems

Lu, Mang; Shan, Zhi; Andrea, Kori A.; MacDonald, Bruce C.; Beale, Stefanie; Curry, Dennis E.; Wang, Li; Wang, Shu Jun; Oakes, Ken D.; Bennett, Craig; Wu, Wenhui; Zhang, Xu

doi:10.1021/acs.langmuir.5b04643

Cited by 27 publications

(24 citation statements)

References 57 publications

(67 reference statements)

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Section: Ldhs Applications In Nucleic Acids (Dna Rna) Deliverymentioning

confidence: 99%

“…In this regard, the small interfering RNA (or silencing RNA, siRNA) therapy is hampered by the barriers for siRNA bioavailability to enter into cells cytoplasm and exert their gene silencing activity. In this scenario, LDHs have been demonstrated as an ideal synthetic vector for both DNA and RNA molecules, due to a well-elucidated adsorption mechanism, taking into account that the phosphate backbone of the DNA polymer coordinates with the metal cations of the LDH lattice via the ligand-exchange process [182,183]. The formation of LDH-DNA hybrids for DNA delivery can be obtained either through the incorporation of small DNA molecules and antisense oligonucleotides into the LDH matrix by a simple ion-exchange reaction [184], or by a more general coprecipitation route involving the in situ formation of LDH layers of various ionic compositions around intercalated DNA [185].…”

Section: Ldhs Applications In Nucleic Acids (Dna Rna) Deliverymentioning

confidence: 99%

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Layered Double Hydroxides: A Toolbox for Chemistry and Biology

et al. 2019

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Layered double hydroxides (LDHs) are an emergent class of biocompatible inorganic lamellar nanomaterials that have attracted significant research interest owing to their high surface-to-volume ratio, the capability to accumulate specific molecules, and the timely release to targets. Their unique properties have been employed for applications in organic catalysis, photocatalysis, sensors, drug delivery, and cell biology. Given the widespread contemporary interest in these topics, time-to-time it urges to review the recent progresses. This review aims to summarize the most recent cutting-edge reports appearing in the last years. It firstly focuses on the application of LDHs as catalysts in relevant chemical reactions and as photocatalysts for organic molecule degradation, water splitting reaction, CO2 conversion, and reduction. Subsequently, the emerging role of these materials in biological applications is discussed, specifically focusing on their use as biosensors, DNA, RNA, and drug delivery, finally elucidating their suitability as contrast agents and for cellular differentiation. Concluding remarks and future prospects deal with future applications of LDHs, encouraging researches in better understanding the fundamental mechanisms involved in catalytic and photocatalytic processes, and the molecular pathways that are activated by the interaction of LDHs with cells in terms of both uptake mechanisms and nanotoxicology effects.

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Section: Ldhs Applications In Nucleic Acids (Dna Rna) Deliverymentioning

confidence: 99%

Section: Ldhs Applications In Nucleic Acids (Dna Rna) Deliverymentioning

confidence: 99%

Layered Double Hydroxides: A Toolbox for Chemistry and Biology

et al. 2019

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“…An efficient siRNA delivery vehicle is necessary to knockdown the expression of PD-L1 on tumor cells or PD-1 on the T cells. For gene delivery, many types of nanoparticles (NPs), such as polymeric NPs (PEI), biomolecular NPs (PLGA and BSA), and inorganic NPs (Au, carbon, and SiO 2 ) are extensively investigated [5], while two inorganic nanoparticles (NPs), i.e., layered double hydroxide (LDH) [6,7,8,9,10] and lipid-coated calcium phosphate (LCP) [11,12,13,14,15], both with many suitable properties, appear as efficient delivery vehicles for the functional siRNA.…”

Section: Introductionmentioning

confidence: 99%

“…LDH is a group of anionic clay materials that have attracted increasing attention in recent years for biomedical applications, such as gene delivery, vaccine delivery, and drug delivery [6,7,8,9,10,16,17]. In particular, MgAl-LDH nanoparticles (NPs) have been demonstrated as efficient vehicles for the delivery of genes and drugs to cells [6,7,8,9,10,16], which are biocompatible, have a high loading capacity, and release target biomolecules in a pH-dependent manner [17,18]. More advantages of LDH NPs as delivery vehicles include the low toxicity, protection of payloads, and their high cellular delivery efficacy [7,10,17,19].…”

Section: Introductionmentioning

confidence: 99%

Enhancing PD-1 Gene Silence in T Lymphocytes by Comparing the Delivery Performance of Two Inorganic Nanoparticle Platforms

et al. 2019

Nanomaterials

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Suitable carriers are crucial to RNAi applications for cancer genotherapy and T-cell immunotherapy. In this research, we selected two extensively-investigated biocompatible inorganic nanoparticle carriers, i.e., layered double hydroxide (LDH) and lipid-coated calcium phosphate (LCP) and then compared their efficacy for siRNA delivery in T cells, in order to understand which carrier is more efficient in delivering functional programmed cell death protein 1 siRNA (PD-1 siRNA) to suspended T lymphocytes. Both LDH and LCP nanoparticles quickly delivered gene segment to mouse T cell lines (EL4), while the LCP nanoparticles exhibited more cellular uptake and higher PD-1 gene silence efficiency. We further demonstrated that LCP nanoparticles successfully reduced the expression of PD-1 in human ex vivo tumor infiltrating lymphocytes (TILs). Thus, LCP nanoparticles can be used as a better nano-carrier for gene therapy in lymphocytes, especially in regards to TIL-related cancer immunotherapy.

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“…Layered double hydroxides (LDHs), also known as anionic clay, have been shown to be an efficient delivery vehicle for anionic drugs and nucleic acids [50][51][52]. LDH is able to intercalate anionic drugs and biomolecules (such as ibuprofen, nucleotides, DNA, RNA and anionic peptides) between the brucite-like layers with high loading, providing protection against degradation [53,54].…”

Section: Layered Double Hydroxide Nanoparticlesmentioning

confidence: 99%

Developing inorganic nanoplatforms for efficient siRNA delivery to improve cancer immunotherapy

Wu¹

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For many decades, cancer treatments basically include surgery, chemotherapy and radiation therapy. Over the last decade, targeted therapies using small molecules have been also included in treatments many cancers. Recently, the development of immune checkpoints and adoptive cell transfer cellbased methods has largely changed the paradigm of cancer treatments, while the new methods are still accompanied with the low responsive rate in solid tumour, high recurrence rate, serious adverse effects and expense for patients. Thus, a more effective immunotherapy is required. One possible solution is to silence the inhibitory immune checkpoints (such as programmed cell death-1: PD-1 and programmed cell death ligand 1: PD-L1) on T cells with small interfering RNA (siRNA), which requires more effective and workable siRNA delivery systems. This PhD project aims to develop effective nano-carriers to deliver functional siRNA to T cells to silence inhibitory immune checkpoints and thus enhance their killing efficacy to cancer cells. By taking advantages of the low toxicity, good biocompatibility, excellent colloidal stability and efficient cellular uptake, MgAl-layered double hydroxide (MgAl-LDH) and lipid-coated calcium phosphate (LCP) nanoparticles (NPs) are examined and compared as nanoplatforms for cancer immunotherapy. This project first optimised the LDH-based delivery system by examining the delivery effects of operation parameters, including the loading method of siRNA by LDH NPs, the LDH:siRNA mass ratio and incubation time. siRNA molecules directly mixed with LDH followed by a dilution with culture medium resulted in >80% cells being transfected in 4 h. MCF-7 cells took up most dsDNA or siRNA at the LDH/gene mass ratio of 10:1-20:1. However, the most suitable LDH:siRNA mass ratio was around 5:1 for efficiently silencing PD-L1 gene due to the control release of siRNA from LDH-siRNA complexes in cytosol. Subsequently, the PD-1 silencing in T lymphoma cell line EL4 and human tumour infiltrating lymphocytes (TILs) was examined using LDH and LCP NPs in order to compare their capability for gene silence in T cell. Under similar conditions, LCP NPs more efficiently delivered siRNA to EL4 cells and silenced the PD-1 gene. The better transfection ability of LCP NPs was also confirmed in TILs to knockdown the PD-1 expression.

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Chemisorption Mechanism of DNA on Mg/Fe Layered Double Hydroxide Nanoparticles: Insights into Engineering Effective SiRNA Delivery Systems

Cited by 27 publications

References 57 publications

Layered Double Hydroxides: A Toolbox for Chemistry and Biology

Layered Double Hydroxides: A Toolbox for Chemistry and Biology

Enhancing PD-1 Gene Silence in T Lymphocytes by Comparing the Delivery Performance of Two Inorganic Nanoparticle Platforms

Developing inorganic nanoplatforms for efficient siRNA delivery to improve cancer immunotherapy

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