Comparison of Avidin, Neutravidin, and Streptavidin as Nanocarriers for Efficient siRNA Delivery

Jain, Akshay; Barve, Ashutosh; Zhao, Zhen; Jin, Wei; Cheng, Kun

doi:10.1021/acs.molpharmaceut.6b00933

Cited by 62 publications

(68 citation statements)

References 47 publications

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“…In contrast, endogenously present molecules for instance vitamins, like biotin, appear to be ideal tags. Previously described avidin-and streptavidin-based CARs (19,20) targeted to biotin is unlikely to be translatable into the clinic, since avidin (egg-protein) as well as streptavidin (bacterial derived protein) are likely to be immunogenic (37,38). Potentially low immunogenicity of the AdCAR-T system will have to be demonstrated in clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Novel Adapter CAR-T cell Technology for precisely controllable Multiplex Cancer Targeting

Seitz

Mittelstaet

Hau

et al. 2020

Preprint

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Chimeric antigen receptor (CAR)-T therapy holds great promise to sustainably improve cancer treatment. However, currently, a broad applicability of CAR-T cell therapies is hampered by limited CAR-T cell versatility and tractability and the lack of exclusive target antigens to discriminate cancerous from healthy tissues. To achieve temporal and qualitative control on CAR-T function, we engineered the Adapter CAR (AdCAR) system. AdCAR-T are redirected to surface antigens via biotin-labeled adapter molecules in the context of a specific linker structure, referred to as Linker-Label-Epitope. AdCAR-T execute highly specific and controllable effector function against a multiplicity of target antigens. In mice, AdCAR-T durably eliminate aggressive lymphoma. Importantly, AdCAR-T might prevent antigen evasion by combinatorial simultaneous or sequential targeting of multiple antigens and are capable to identify and differentially lyse cancer cells by integration of adapter molecule mediated signals based on multiplex antigen expression profiles.

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Section: Discussionmentioning

confidence: 99%

Novel Adapter CAR-T cell Technology for precisely controllable Multiplex Cancer Targeting

Seitz

Mittelstaet

Hau

et al. 2020

Preprint

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“…The key remaining challenge for RNAi therapy is how to deliver siRNA to the target cells. Nanoparticles, cation lipid, cation polymers and other novel delivery systems such as avidin-biotin complex have been studied for siRNA delivery 25 , 41 - 43 . Among them, siRNA conjugate is a promising approach and some of them are evaluated in clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Discovery of Aptamer Ligands for Hepatic Stellate Cells Using SELEX

Chen¹,

Líu²,

Jain³

et al. 2017

Theranostics

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Insulin like growth factor II receptor (IGFIIR) is a transmembrane protein overexpressed in activated hepatic stellate cells (HSCs), which are the major target for the treatment of liver fibrosis. In this study, we aim to discover an IGFIIR-specific aptamer that can be potentially used as a targeting ligand for the treatment and diagnosis of liver fibrosis. Systematic evolution of ligands by exponential enrichment (SELEX) was conducted on recombinant human IGFIIR to identify IGFIIR-specific aptamers. The binding affinity and specificity of the discovered aptamers to IGFIIR and hepatic stellate cells were studied using flow cytometry and Surface Plasmon Resonance (SPR). Aptamer-20 showed the highest affinity to recombinant human IGFIIR protein with a Kd of 35.5 nM, as determined by SPR. Aptamer-20 also has a high affinity (apparent Kd 45.12 nM) to LX-2 human hepatic stellate cells. Binding of aptamer-20 to hepatic stellate cells could be inhibited by knockdown of IGFIIR using siRNA, indicating a high specificity of the aptamer. The aptamer formed a chimera with an anti-fibrotic PCBP2 siRNA and delivered the siRNA to HSC-T6 cells to trigger silencing activity. In Vivo biodistribution study of the siRNA-aptamer chimera also demonstrated a high and specific uptake in the liver of the rats with CCl4-induced liver fibrosis. These data suggest that aptamer-20 is a high-affinity ligand for antifibrotic and diagnostic agents for liver fibrosis.

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“…Since TNF-α and IL-6 are considered as highly important markers in inflammation because they are involved and overexpressed in most inflammatory states, we decided to assess TNF-α and IL-6 protein secretion in LPS-stimulated Mϕ pretreated with PEG-LNP(Cal) and targeted PEG-LNP(Cal) by ELISA. 41 Both PEG-LNP(Cal) and targeted PEG-LNP(Cal) significantly suppressed TNF-α secretion in a dose-dependent manner as compared to treatment with free calcitriol in LPS-stimulated Mϕ (data not shown). Similarly, IL-6 secretion was slightly reduced, albeit not significantly, after treatment with both PEG-LNP(Cal) and targeted PEG-LNP(Cal) ( Figure 3G and H).…”

Section: Effects Of Encapsulated Calcitriol On Proinflammatory Cytokimentioning

confidence: 94%

<p>Targeted lipid nanoparticle delivery of calcitriol to human monocyte-derived macrophages in vitro and in vivo: investigation of the anti-inflammatory effects of calcitriol</p>

Rafique¹,

Etzerodt²,

Graversen³

et al. 2019

IJN

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Background: Vitamin D 3 possesses anti-inflammatory and modulatory properties in addition to its role in calcium and phosphate homeostasis. Upon activation, macrophages (M) can initiate and sustain pro-inflammatory cytokine production in inflammatory disorders and play a pathogenic role in certain cancers. Purpose: The main purpose of this study was to encapsulate and specifically target calcitriol to macrophages and investigate the anti-inflammatory properties of calcitriol in vitro and in vivo. Methods: In this study we have designed and developed near-infrared calcitriol PEGylated nanoparticles (PEG-LNP(Cal)) using a microfluidic mixing technique and modified lipid nanoparticles (LNPs) to target the M specific endocytic receptor CD163. We have investigated LNP cellular uptake and anti-inflammatory effect in LPS-induced M in vitro by flow cytometry, confocal microscopy and gene expression analyses. LNP pharmacodynamics, bio-distribution and organ specific LNP accumulation was also investigated in mice in vivo. Results: In vitro, we observed the specific uptake of PEG-LNP(Cal)-hCD163 in human M, which was significantly higher than the non-specific uptake of control PEG-LNP(Cal)-IgG(h) in M. Pretreatment with encapsulated calcitriol was able to attenuate intracellular TNF-expression, and M surface marker HLA-DR expression more efficiently than free calcitriol in LPS-induced M in vitro. Encapsulated calcitriol diminished mRNA gene levels of TNF-, NF-B, MCP-1 and IL-6, while upregulating IL-10. TNF-and IL-6 protein secretion also decreased. In mice, an in vivo pharmacodynamic study of PEG-LNP(Cal) showed a rapid clearance of IgG and CD163 modified LNPs compared to PEG-LNP(Cal). Antibody modified PEG-LNP(Cal) accumulated in the liver, spleen and kidney, whereas unmodified PEG-LNP(Cal) accumulation was only observed in the liver. Conclusion: Our results show that calcitriol can be effectively targeted to M. Our data confirms the anti-inflammatory properties of calcitriol and this may be a potential way to deliver high dose bioactive calcitriol to M during inflammation in vivo.

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Comparison of Avidin, Neutravidin, and Streptavidin as Nanocarriers for Efficient siRNA Delivery

Cited by 62 publications

References 47 publications

Novel Adapter CAR-T cell Technology for precisely controllable Multiplex Cancer Targeting

Novel Adapter CAR-T cell Technology for precisely controllable Multiplex Cancer Targeting

Discovery of Aptamer Ligands for Hepatic Stellate Cells Using SELEX

<p>Targeted lipid nanoparticle delivery of calcitriol to human monocyte-derived macrophages in vitro and in vivo: investigation of the anti-inflammatory effects of calcitriol</p>

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