Shear Stress-Enhanced Internalization of Cell Membrane Proteins Indicated by a Hairpin-Type DNA Probe

He, Ziyi; Zhang, Wanling; Mao, Sifeng; Li, Nan; Li, Haifang; Lin, Jin‐Ming

doi:10.1021/acs.analchem.8b00755

Cited by 38 publications

(18 citation statements)

References 30 publications

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“…We herein propose that DONs with certain framework [ 39 ] could serve as an ideal scaffold for ADCs analogues with exceptional control over targeting ligand density and drug loading contents for optimized antitumor efficacies and safety profile. [ 40 ] Specifically, we construct a new prostate cancer (PCa)‐specific drug delivery system by introducing different numbers of ligand 2‐[3‐(1,3‐dicarboxy propyl)‐ureido] pentanedioic acid (DUPA) to a designed six‐helical‐bundle DNA origami nanostructure (6HB DON). DUPA has been demonstrated to be a high‐affinity inhibitor ( K i ≈ 0.02 × 10 −9 –0.1 × 10 −9 m ) for prostate‐specific membrane antigen (PSMA).…”

Section: Introductionmentioning

confidence: 99%

DNA Origami‐Enabled Engineering of Ligand–Drug Conjugates for Targeted Drug Delivery

Guo

et al. 2020

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under the context that Brentuximab vedotin (Adcetris) for relapsed Hodgkin lymphoma [5,6] and T-DM1 (Kadcyla) for HER2 + metastatic breast cancer [7,8] received clinical approval from the Food and Drug Administration (FDA). The socalled "magic bullet," originally conceived by Paul Ehrlich, [9] are designed to combine the toxicity of small-molecule drugs with the targeting ability of antibodies to improve overall efficacy and therapeutic index. [10][11][12][13][14][15] Although conceptually straightforward, development of ADCs is encountered with several challenges including manageable toxicity, homogeneous conjugation and limited drug payload capacity. The balance between drug-to-antibody ratio (DAR) and targeting capability is mandatory for ADCs to reduce the attrition rate of drug candidates. Very high DAR ADCs may suffer decreased recognition to the target antigen. [16][17][18][19] Hence, it is highly desirable to develop ADCs with both high maximum tolerated doses and high selectivity. [20][21][22] Recently, the bloom of structural DNA nanotechnology [23,24] has demonstrated unprecedented precision on structural control, which enables predictable and programmable construction of complex nanostructures by exploiting intra-and inter-molecular Watson-Crick base-pairing. The programmability and addressability of DNA origami nanostructures (DONs) enable multiple desired functional moieties (such as therapeutic cargoes and tumor targeting ligands) with designer geometry and density. [25][26][27] Therefore, DONs have been increasingly employed for developing novel drug delivery systems [28,29] due to their versatile designability, high solubility, and intrinsic biocompatibility. [30][31][32][33][34][35][36][37] Moreover, certain types of DONs have been proven to be readily rapidly internalized by mammalian cells despite their negatively charged surface property. [38] We herein propose that DONs with certain framework [39] could serve as an ideal scaffold for ADCs analogues with exceptional control over targeting ligand density and drug loading contents for optimized antitumor efficacies and safety profile. [40] Specifically, we construct a new prostate cancer (PCa)specific drug delivery system by introducing different numbers of ligand 2-[3-(1,3-dicarboxy propyl)-ureido] pentanedioic acid (DUPA) to a designed six-helical-bundle DNA origami nanostructure (6HB DON). DUPA has been demonstrated to be a high-affinity inhibitor (K i ≈ 0.02 × 10 −9 -0.1 × 10 −9 m) for prostate-specific membrane antigen (PSMA). [41] We incorporate this Effective drug delivery systems that can systematically and selectively transport payloads to disease cells remain a challenge. Here, a targeting ligandmodified DNA origami nanostructure (DON) as an antibody-drug conjugate (ADC)-like carrier for targeted prostate cancer therapy is reported. Specifically, DON of six helical bundles is modified with a ligand 2-[3-(1,3-dicarboxy propyl)-ureido] pentanedioic acid (DUPA) against prostate-specific membrane antigen (PSMA), to serve as the antibody f...

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Section: Introductionmentioning

confidence: 99%

DNA Origami‐Enabled Engineering of Ligand–Drug Conjugates for Targeted Drug Delivery

Guo

et al. 2020

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“…The caveolae-based internalization pathway contains ubiquitin ligase Smurf2 bound receptors and was proposed to shut down the BMP/TGFβ-SMAD signaling [ 91 ], while others showed that BMP-SMAD signaling could be initiated from receptors residing within caveolae [ 94 , 95 ]. Importantly, physical stimuli, such as substrate stiffness sensed by ECs, were sufficient to induce caveolin-dependent endocytosis of membrane receptors [ 96 , 97 , 98 ]. Mechanistically, ALK1 and BMPR2 localize within caveolae, while Alk1 physically interacts with caveolin-1 (cav-1) through cav-1′s scaffolding domain, suggesting a joint contribution of ALK1, BMPR2, and cav-1, as the key mediators of BMP9/10 signaling [ 99 , 100 , 101 ] ( Figure 1 f).…”

Section: Activating Versus Homeostatic Tgfβ/bmp Signaling In Endotmentioning

confidence: 99%

It Takes Two to Tango: Endothelial TGFβ/BMP Signaling Crosstalk with Mechanobiology

Hiepen

Mendez

Knaus

2020

Cells

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Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta (TGFβ) superfamily of cytokines. While some ligand members are potent inducers of angiogenesis, others promote vascular homeostasis. However, the precise understanding of the molecular mechanisms underlying these functions is still a growing research field. In bone, the tissue in which BMPs were first discovered, crosstalk of TGFβ/BMP signaling with mechanobiology is well understood. Likewise, the endothelium represents a tissue that is constantly exposed to multiple mechanical triggers, such as wall shear stress, elicited by blood flow or strain, and tension from the surrounding cells and to the extracellular matrix. To integrate mechanical stimuli, the cytoskeleton plays a pivotal role in the transduction of these forces in endothelial cells. Importantly, mechanical forces integrate on several levels of the TGFβ/BMP pathway, such as receptors and SMADs, but also global cell-architecture and nuclear chromatin re-organization. Here, we summarize the current literature on crosstalk mechanisms between biochemical cues elicited by TGFβ/BMP growth factors and mechanical cues, as shear stress or matrix stiffness that collectively orchestrate endothelial function. We focus on the different subcellular compartments in which the forces are sensed and integrated into the TGFβ/BMP growth factor signaling.

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“…[ 72 ] Further, Lin and coworkers developed a cell surface‐anchored DNA probe for investigating the regulating effects of fluid shear stress on membrane protein internalization and the cell endocytosis process. [ 74 ] In addition to the different detection strategies of DNA‐CRNs demonstrated earlier for monitoring of the cellular microenvironment, DNA‐CRNs also play essential roles in cell‐based biocomputation, which has great potential in cancer diagnosis. [ 80 ]…”

Section: Detection Strategies Of Dna‐crns For Monitoring Of the Cellumentioning

confidence: 99%

DNA‐Based Chemical Reaction Networks for Biosensing Applications

Jiang

Yuan

et al. 2020

Advanced Intelligent Systems

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The nature of biosensing is a biochemical reaction. DNA‐based chemical reaction networks (DNA‐CRNs) as a powerful programming language for describing behaviors of chemical reactions have shown great potential in designs and applications of biosensors. Due to their programmability, modularity, and versatility of the DNA strand, the performance of different detection strategies can be improved mainly by the rational design of DNA‐CRNs. Herein, an overview of the fundamental theory and biosensing processes of DNA‐CRNs is provided. Various detection strategies of DNA‐CRNs are introduced, either in a simple low‐order reaction model or in a complicated high‐order reaction type, in combination with some typical cases for the different detection purposes. In addition, an overview of the recent development of DNA‐CRNs for monitoring the cell microenvironment is presented, which is of significance to uncover some specific cell behaviors and functions. Finally, the roles of DNA‐CRNs in the rational design of high‐performance biosensors are summarized by pointing out the remaining challenges that impede the precise biosensing using DNA‐CRNs in complicated biological environments.

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Shear Stress-Enhanced Internalization of Cell Membrane Proteins Indicated by a Hairpin-Type DNA Probe

Cited by 38 publications

References 30 publications

DNA Origami‐Enabled Engineering of Ligand–Drug Conjugates for Targeted Drug Delivery

DNA Origami‐Enabled Engineering of Ligand–Drug Conjugates for Targeted Drug Delivery

It Takes Two to Tango: Endothelial TGFβ/BMP Signaling Crosstalk with Mechanobiology

DNA‐Based Chemical Reaction Networks for Biosensing Applications

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