Shear-Activated Nanotherapeutics for Drug Targeting to Obstructed Blood Vessels

Korin, Netanel; Kanapathipillai, Mathumai; Matthews, Benjamin D.; Crescente, Marilena; Brill, Alexander; Mammoto, Tadanori; Ghosh, Kaustabh; Jurek, Samuel; Bencherif, Sidi A.; Bhatta, Deen; Coskun, Ahmet U.; Feldman, Charles L.; Wagner, Denisa D.; Ingber, Donald E.

doi:10.1126/science.1217815

Cited by 460 publications

(459 citation statements)

References 31 publications

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“…S6. In this respect, one can also think of designing clusters with prescribed yielding behaviour that would respond to flow in a very precise way and change their chemical characteristics by exposing hidden chemical groups 30 . In terms of optical properties, it could be possible to use these random aggregates as pigments 31 .…”

Section: Discussionmentioning

confidence: 99%

Blood-clotting-inspired reversible polymer–colloid composite assembly in flow

et al. 2013

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Blood clotting is a process by which a haemostatic plug is assembled at the site of injury. The formation of such a plug, which is essentially a (bio)polymer-colloid composite, is believed to be driven by shear flow in its initial phase, and contrary to our intuition, its assembly is enhanced under stronger flowing conditions. Here, inspired by blood clotting, we show that polymer-colloid composite assembly in shear flow is a universal process that can be tailored to obtain different types of aggregates including loose and dense aggregates, as well as hydrodynamically induced 'log'-type aggregates. The process is highly controllable and reversible, depending mostly on the shear rate and the strength of the polymer-colloid binding potential. Our results have important implications for the assembly of polymercolloid composites, an important challenge of immense technological relevance. Furthermore, flow-driven reversible composite formation represents a new paradigm in non-equilibrium self-assembly.

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Section: Discussionmentioning

confidence: 99%

Blood-clotting-inspired reversible polymer–colloid composite assembly in flow

et al. 2013

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“…Through mimicking the mechanical stimuli-responsive function of platelets for changing shape in response to high shear control, a recent approach aims to treat obstructed blood vessels through shearcontrolled release of nanotherapeutics (Fig. 5a) 89 . The approach used intravenously injected microscale aggregates constructed from smaller therapeutic nanoparticles (Fig.…”

Section: Engineering Of Biomimetic Systemsmentioning

confidence: 99%

The role of mechanics in biological and bio-inspired systems

et al. 2015

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Natural systems frequently exploit intricate multiscale and multiphasic structures to achieve functionalities beyond those of man-made systems. Although understanding the chemical make-up of these systems is essential, the passive and active mechanics within biological systems are crucial when considering the many natural systems that achieve advanced properties, such as high strength-to-weight ratios and stimuli-responsive adaptability. Discovering how and why biological systems attain these desirable mechanical functionalities often reveals principles that inform new synthetic designs based on biological systems. Such approaches have traditionally found success in medical applications, and are now informing breakthroughs in diverse frontiers of science and engineering. N atural biological systems are constrained by a limited number of chemical building blocks, yet through practical material organization and mechanics 1 , fulfil the functional needs of diverse organisms by methods that often exceed what is currently achievable using man-made approaches 2 . Synthetic systems are often limited by trade-offs where improving one property comes at the expense of another, as observed when utilizing ceramics in place of metals where a higher elastic modulus is accompanied by lower fracture toughness. However, many natural systems and materials have evolved 3 solutions that result in a number of improved properties simultaneously (for example, high modulus with high fracture toughness), and often produce systems that fulfil multiple functions concurrently. For example, stomatopod dactyl clubs 4 tolerate exceptional amounts of damage through multiphasic material interfaces, and efficient blood-clotting mechanisms are achieved through platelet shape adaptability 5 . These intricate mechanics phenomena, relating material organization and adaptability, are implemented in a structurally minimalistic fashion that is difficult to emulate through artificial manufacturing approaches 6 . Such mechanical functions (that is, mechanofunctionality) of biological systems are not isolated cases-multiscale structural organization also contributes to the hardness of nacre 7 and toughness of toucan beaks 8 , while shape changing commonly drives behaviour in many sea creatures 9 and plants 10 . As such recurrent, mechanically based organizational features throughout biology are discovered and analysed, they provide insight for building exceptional mechanofunctionalities into synthetic, bio-inspired technologies.The survival of organisms is often heightened by structures and materials with favourable properties (for example, load-bearing capacity) or mechanofunctionalities that are passive

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“…Current strategies trigger the release of NPs from carriers via enzymes, 1 magnetic fields 2 and shear stress. 3 However, these methods are limited to specific organs/tissues, such as blocked blood vessels. A more versatile technology is desired that allows the targeted delivery of NPs to any organ/tissue while maintaining traceability using a non-invasive imaging modality.…”

Section: Introductionmentioning

confidence: 99%

Controlled nanoparticle release from stable magnetic microbubble oscillations

Gao

Chan

et al. 2016

NPG Asia Mater

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Magnetic microbubbles (MMBs) are microbubbles (MBs) coated with magnetic nanoparticles (NPs). MMBs not only maintain the acoustic properties of MBs, but also serve as an important contrast agent for magnetic resonance imaging. Such dual-modality functionality makes MMBs particularly useful for a wide range of biomedical applications, such as localized drug/gene delivery. This article reports the ability of MMBs to release their particle cargo on demand under stable oscillation. When stimulated by ultrasound at resonant frequencies, MMBs of 450 nm to 200 μm oscillate in volume and surface modes. Above an oscillation threshold, NPs are released from the MMB shell and can travel hundreds of micrometers from the surface of the bubble. The migration of NPs from MMBs can be described with a force balance model. With this technology, we deliver doxorubicincontaining poly(lactic-co-glycolic acid) particles across a physiological barrier both in vitro and in vivo, with a 18-fold and 5-fold increase in NP delivery to the heart tissue of zebrafish and tumor tissue of mouse, respectively. The penetration of released NPs in tissues is also improved. The ability to remotely control the release of NPs from MMBs suggests opportunities for targeted drug delivery through/into tissues that are not easily diffused through or penetrated. NPG Asia Materials (2016) 8, e260; doi:10.1038/am.2016.37; published online 8 April 2016 INTRODUCTIONTargeted drug delivery and controlled release is the 'holy grail' of nanomedicine. In this regard, one emerging strategy employs a localized stimulus to precisely deposit drug-containing nanoparticles (NPs) at the tissue/organ of interest. The deposited NPs then continuously release drug molecules in a localized and sustained manner. Current strategies trigger the release of NPs from carriers via enzymes, 1 magnetic fields 2 and shear stress. 3 However, these methods are limited to specific organs/tissues, such as blocked blood vessels. A more versatile technology is desired that allows the targeted delivery of NPs to any organ/tissue while maintaining traceability using a non-invasive imaging modality.The present paper reports a strategy toward this end. Magnetic microbubbles (MMBs), the combination of multi-modal contrastenhanced imaging (both magnetic resonance imaging and ultrasound imaging) with targeted drug delivery (magnetic targeting) and controlled release (bubble cavitation) at any site of interest represents an emerging theranostic platform. However, the current formulations of MMBs, stabilized by a polymeric, lipid or silica shell, need a high acoustic energy field to trigger the release through bubble

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Shear-Activated Nanotherapeutics for Drug Targeting to Obstructed Blood Vessels

Cited by 460 publications

References 31 publications

Blood-clotting-inspired reversible polymer–colloid composite assembly in flow

Blood-clotting-inspired reversible polymer–colloid composite assembly in flow

The role of mechanics in biological and bio-inspired systems

Controlled nanoparticle release from stable magnetic microbubble oscillations

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