3D Printed Microtransporters: Compound Micromachines for Spatiotemporally Controlled Delivery of Therapeutic Agents

Huang, Tian-Yun; Sakar, Mahmut Selman; Mao, Angelo S.; Petruska, Andrew J.; Qiu, Fuming; Chen, Xuebo; Kennedy, Stephen; Mooney, David J.; Nelson, Bradley J.

doi:10.1002/adma.201503095

Cited by 201 publications

(171 citation statements)

References 49 publications

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“…Global actuation refers to control schemes that affect the position or orientation of the robot relative to its surroundings, and this is often used to control swarms of microrobots to navigate about their environment. Local actuation, on the other hand, induces relative motion between different parts of the robot mechanism, resulting in pushing/pulling along an axis or rotation about a hinge (e.g., rotational actuation to expel a payload) …”

Section: Introductionmentioning

confidence: 99%

A Monolithic Force‐Sensitive 3D Microgripper Fabricated on the Tip of an Optical Fiber Using 2‐Photon Polymerization

Power

Thompson

Anastasova

et al. 2018

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102

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Microscale robotic devices have myriad potential applications including drug delivery, biosensing, cell manipulation, and microsurgery. In this work, a tethered, 3D, compliant grasper with an integrated force sensor is presented, the entirety of which is fabricated on the tip of an optical fiber in a single-step process using 2-photon polymerization. This gripper can prove useful for the interrogation of biological microstructures such as alveoli, villi, or even individual cells. The position of the passively actuated grasper is controlled via micromanipulation of the optical fiber, and the microrobotic device measures approximately 100 µm in length and breadth. The force estimation is achieved using optical interferometry: high-dimensional spectral readings are used to train artificial neural networks to predict the axial force exerted on/by the gripper. The design, characterization, and testing of the grasper are described and its real-time force-sensing capability with an accuracy below 2.7% of the maximum calibrated force is demonstrated.

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Section: Introductionmentioning

confidence: 99%

A Monolithic Force‐Sensitive 3D Microgripper Fabricated on the Tip of an Optical Fiber Using 2‐Photon Polymerization

Power

Thompson

Anastasova

et al. 2018

Small

102

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“…Considerable progress has been made recently towards the development of synthetic nano/micromachines with attractive capabilities for diverse biomedical applications, 1–3 including biosensing, 4–6 cargo delivery, 7–9 nanosurgery, 10,11 and detoxification. 12,13 The attractive movement, cargo-towing, and navigation functions of different self-propelled and externally-powered nano/micromotors 1,14–18 have led to their growing use for active transport and delivery of therapeutic payloads, compared to common diffusion-based passive approaches.…”

Section: Introductionmentioning

confidence: 99%

Nanomotor-Enabled pH-Responsive Intracellular Delivery of Caspase-3: Toward Rapid Cell Apoptosis

et al. 2017

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Direct and efficient intracellular delivery of enzymes to cytosol holds tremendous therapeutic potential while remaining an unmet technical challenge. Herein, an ultrasound (US)-propelled nanomotor approach and a high pH-responsive delivery strategy is reported to overcome such challenge using caspase-3 (CASP-3) as a model enzyme. Consisting of a gold nanowire (AuNW) motor with a pH-responsive polymer coating, in which the CASP-3 is loaded, the resulting nanomotor protects the enzyme from release and deactivation prior to reaching an intracellular environment. However, upon entering a cell and exposure to the higher intracellular pH, the polymer coating is dissolved, thereby directly releasing the active CASP-3 enzyme to the cytosol and causing rapid cell apoptosis. In vitro studies using gastric cancer cells as a model cell line demonstrates that such motion-based active delivery approach leads to remarkably high apoptosis efficiency within significantly shorter time and lower amount of CASP-3 compared to other control groups without involving US-propelled nanomotors. For instance, the reported nanomotor system can achieve 80% apoptosis of human gastric adenocarcinoma (AGS) cells within only 5 min, which dramatically outperforms other CASP-3 delivery approaches. These results indicate that the US-propelled nanomotors may act as a powerful vehicle for cytosolic delivery of active therapeutic proteins, which would offer an attractive means to enhance the current landscape of intracellular protein delivery and therapy. While CASP-3 is selected as a model protein in this study, the same nanomotor approach can be readily applied to a variety of different therapeutic proteins.

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“…Rastering the laser focus throughout the photoresist in three dimensions then enables the creation of polymer structures with virtually any geometry. [7-9] This architectural versatility renders these 3D polymer structures useful for many technological applications, including drug delivery, [10-12] tissue engineering, [13-15] micro/nano-optics [16-17] and photonics. [18-19] …”

Section: Introductionmentioning

confidence: 99%

Functionalized 3D Architected Materials via Thiol‐Michael Addition and Two‐Photon Lithography

et al. 2017

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Graphical abstract A facile method of fabricating functionalized 3D architected materials is achieved by using functionalized acrylates synthesized via thiol-Michael addition, which are then polymerized using two-photon lithography. A wide variety of functional groups can be attached, from Boc-protected amines to fluoroalkanes. Modification of surface wetting properties and conjugation with fluorescent tags are demonstrated to highlight the potential applications of this technique.

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3D Printed Microtransporters: Compound Micromachines for Spatiotemporally Controlled Delivery of Therapeutic Agents

Cited by 201 publications

References 49 publications

A Monolithic Force‐Sensitive 3D Microgripper Fabricated on the Tip of an Optical Fiber Using 2‐Photon Polymerization

A Monolithic Force‐Sensitive 3D Microgripper Fabricated on the Tip of an Optical Fiber Using 2‐Photon Polymerization

Nanomotor-Enabled pH-Responsive Intracellular Delivery of Caspase-3: Toward Rapid Cell Apoptosis

Functionalized 3D Architected Materials via Thiol‐Michael Addition and Two‐Photon Lithography

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