Nano Today
Volume 11, Issue 1, February 2016, Pages 31-40
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Review
Using the power of organic synthesis for engineering the interactions of nanoparticles with biological systems

https://doi.org/10.1016/j.nantod.2015.11.002Get rights and content

Highlights

  • Surface properties are a key determinant of the biological properties of nanomaterials.

  • Organic synthesis provides atom-by-atom control over nanomaterial surfaces.

  • The control of nanoparticle surfaces is an important tool for the creation of diagnostics and therapeutics.

Summary

The surface properties of nanoparticles (NPs) dictate their interaction with the outside world. The use of precisely designed molecular ligands to control NP surface properties provides an important toolkit for modulating their interaction with biological systems, facilitating their use in biomedicine. In this review we will discuss the application of the atom-by-atom control provided by organic synthesis to the generation of engineered nanoparticles, with emphasis on how the functionalization of NPs with these “small” organic molecules (Mw <1000) can be used to engineer NPs for a wide range of applications.

Introduction

Fabricating nanoparticles (NPs) with unique biological properties is a challenging but rewarding task [1], [2], [3]. The combination of multiple NP features such as core size [4], [5], [6], [7], shape [8], [9], [10], and surface chemistry [11], [12] allows the regulation of the biological behavior. The NP surface is the interface with the outside world, and plays a prominent role in the interaction with biomolecules. The relatively large surface area of NPs facilitate the attachment of a wide range of biomacromolecules such as peptides [13], [14], proteins [15], [16], nucleic acids [17], [18], and viruses [19] to dictate NP-protein or NP-cell interactions. Likewise, polymers have been widely employed as NP coverages [20]. The structural complexity and/or potential biodegradability of these macromolecular systems, however, introduce complexity to the interactions between NPs and biomolecules.

The use of non-polymeric “small” organic molecules provides a robust and scalable methodology to tailor the nano-bio interface. The wide variety of moieties available through organic chemistry provides a rich toolkit to provide atom-by-atom control of the NP-biomolecule interactions [21], [22], [23]. In this review we will present research focusing on controlling the interactions of NPs with proteins and cells by using these “small” molecule (Mw <1000) ligands.

Section snippets

Modulating the Interaction between NPs and biological systems

The interaction modes of NPs with proteins and cells can be modified by designing the surface monolayer, concomitantly modulating biological functions [24]. This fine-tuned control provides a finely honed tool for a wide array of biological interactions.

Engineering responsive biological interactions

In addition to “permanent” physicochemical properties, a chemical designing approach can also construct “responsive” surfaces that can alter the physicochemical features of the NPs by endogenous stimuli. Such chemical surfaces generate unique interaction modes with biological systems.

Conclusions and prospective

As shown above, surface chemistry defines the interactions of NPs with biological systems. Building the surface with proper chemical structures has the potential to overcome many challenges currently present in nanomedicine. The examples highlighted in this review clearly show the power of chemical approaches for tailoring the physicochemical properties of NPs, providing fruitful biological features.

Organic chemistry can be utilized as a “palette” containing an unlimited range of functional

Acknowledgements

This work was supported by NSF (CHE-1307021) and the NIH (#GM077173, EB014277). T.M. is grateful to the Japan Society for the Promotion of Sciences (JSPS, Postdoctoral Fellowship for Research Abroad and Strategic Young Researcher Overseas Visits Program for Accelerating Brain Circulation).

Tsukasa Mizuhara received his Ph.D. in Pharmaceutical Science from Kyoto University where he worked in the field of organic chemistry and medicinal chemistry. Currently, he is working as a postdoctoral researcher in the Department of Chemistry at the University of Massachusetts Amherst under the guidance of Professor Vincent M. Rotello. His research interests focus on the fabrication of well-designed chemical surfaces and its application for nanomedicine.

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    Tsukasa Mizuhara received his Ph.D. in Pharmaceutical Science from Kyoto University where he worked in the field of organic chemistry and medicinal chemistry. Currently, he is working as a postdoctoral researcher in the Department of Chemistry at the University of Massachusetts Amherst under the guidance of Professor Vincent M. Rotello. His research interests focus on the fabrication of well-designed chemical surfaces and its application for nanomedicine.

    Daniel F. Moyano received his B.Sc. (honors) in Chemistry at the National University of Colombia, Bogotá, Colombia in 2009. He is currently a Ph.D. candidate in the Chemistry Department at the University of Massachusetts Amherst, under the supervision of Prof. Vincent M. Rotello. His current research focuses on the chemical design of nanoparticle surfaces for modulation of immune responses.

    Vincent Rotello is Goessmann Professor of Chemistry and Distinguished University Professor at the University of Massachusetts-Amherst. He joined the University of Massachusetts in 1993, receiving the NSF CAREER, Cottrell Scholar and Camille Dreyfus Teacher-Scholar awards, the Sloan Fellowship, and the Langmuir Lectureship, and is a Fellow of the AAAS and the Royal Society of Chemistry (U.K.). He is the Editor-in-Chief of Bioconjugate Chemistry, and on the Editorial Board of 12 other journals. His research program focuses on engineering the interface between hard and soft materials for applications in nanotechnology and nanomedicine, with >450 papers published to date.

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