Non-spherical nanostructures in nanomedicine: From noble metal nanorods to transition metal dichalcogenide nanosheets

doi:10.1016/j.apmt.2021.101107

Applied Materials Today

Volume 24, September 2021, 101107

https://doi.org/10.1016/j.apmt.2021.101107 Get rights and content

Highlights

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The geometry of metal-based nanomaterials affects endocytosis.
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Aspect ratio and stiffness of nanometals influence their cellular uptake.
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Non-spherical metal nanoparticles are employed in biomedicine, including regenerative medicine and cancer therapy.

Abstract

Non-spherical metal nanomaterials such as noble metal or transition metal dichalcogenides and MXenes have been employed in different biomedical facets. Because the biological properties of these nanocompounds are governed by their architecture and composition, such factors should be considered prior to their adoption for clinical use. The architecture of metal-based nanomaterials affects cell viability by virtue of the variable geometry of these nanomaterials as well as their physicochemical interactions with mammalian cell membranes. In the present review, the effects of parameters such as interfacial interaction and aspect ratio on cellular uptake of non-spherical metallic nanomaterials will be discussed. The application of these nanomaterials as biosensors, in cancer diagnosis and therapy, tissue engineering and regenerative medicine will also be thoroughly reviewed.

Graphical abstract

Introduction

Metal-based nanomaterials with high thermal/electrical conductivity, strength, melting point, ductility and toughness are ideal candidates for biomedical applications [1,2]. These nanomaterials consist of different forms of metal and metal oxide particles, including noble metals (i.e. Au, Ag and Pt), transition metal dichalcogenides (TMDCs) and MXenes [3,4]. The large surface area, excellent stability, flexible functionalization capacity and optical and conductive properties of these nanomaterials are attributed to their nanosize and material composition [5], [6], [7], [8], [9]. The functional properties of metal-based nanomaterials are affected by their variations in size, architecture, charge and crystallinity [10]. Moreover, the shape and the architecture of metal-based nanomaterials affect their interaction with biological systems. For instance, the shape of nanomaterials also affects their bio-distribution, interactions with blood vessels, transport across endothelial cells, cellular uptake as well as clearance from the human body [11,12]. Precise control of the morphology/geometry of non-spherical nanostructures makes them somewhat prominent. For example, Au nanorods possess more potent photothermal/cancer cell killing capability than spherical Au nanoparticles [13]. Cells’ phagocytic action of non-spherical particles is different compared to their spherical counterparts. For example, ellipsoid particles are uptaken less aggressively by macrophages [14], whereas disk/oblate shaped particles are more susceptible to phagocytosis [15]. In addition, filamentous micelles have a longer circulation time (about 10 times) than spherical micelles [16].

The objective of the present review is to highlight the biomedical utilization of different forms of non-spherical metal nanomaterials. This is achieved by reviewing some of the latest publications in this field. Specifically, the cellular uptake of non-spherical metal nanostructures by different endocytosis pathways, the applications of these nanostructures in the advancement of cancer diagnosis and therapy, various aspects of regenerative medicine, assorted types of biosensors and their future perspectives will be addressed in depth.

Section snippets

Preparation methods of non-spherical nanoparticles

Different methodologies are available for the preparation of non-spherical nanostructures. These methods include mechanical procedures (e.g. particle replication in lithography, film stretching, template assembly) and chemical procedures (e.g. seed growth method, seedless growth method, hydrothermal growth).

Lithography techniques can be separated into two sub-categories: non-wetting templates (particle replication in lithography) and microfluidic systems. The non-wetting features of fluorinated

Cellular uptake of nanomaterials

Adoption of nanomaterials for medical diagnosis and therapy is one of the most promising applications in nanomedicine. The interaction of nanomaterials with biological systems and the optimal design of these nanomaterials with well-defined pharmacokinetics for enhanced cellular uptake and intracellular transport represent major milestones in nanomaterial development. Cellular uptake, or endocytosis, is a cellular process wherein substances are brought into the cell. Because of their small

Endocytosis mechanisms

The development of nanotechnology has led to the creation of a plethora of nanostructures. Intracellular uptake of these nanostructures is strictly dependent on particle properties such as shape, size and surface functionalization, as well as membrane characteristics and particle geometrical properties [58]. Large, micron-sized nanostructures with a size range between 500 nm and 3 μm are internalized via phagocytosis, while smaller nanoparticles preferentially use pinocytosis for uptake.

Effect of nanoparticle aspect ratio on cellular uptake

The effect of aspect ratio on cellular uptake has received the most attention among the various parameters exhibited by nanoparticles. Aspect ratio accounts for the shape of the nanoparticles [110]. There are different and sometimes conflicting opinions regarding the effect of aspect ratio on the uptake of nanomaterials. Whereas some researchers believe that a larger aspect ratio imposes difficulty on cell internalization, others opine that nanoparticles with higher aspect ratios have a better

Interfacial interaction between nanoparticles and cells

The interface between a nanocarrier and the cell surface determines the form of the nanomaterial that can enter the cell and the subsequent form of transport into the cell [130]. Specifically, uptake may be due to simple physical contact, specific interactions or different internalization pathways with cell surface receptors. Free energy analysis shows that the size of nanoparticles determines whether endocytosis can proceed to completion. In addition, the shape of nanoparticles destroys the

Intracellular translocation

After the uptake of nanoparticles into cells, the intracellular location and translocation of nanoparticles are crucial factors that affect the toxicity and performance of the internalized nanoparticles [140]. The nanoparticles are typically translocated through endosomal and/or lysosomal vesicles that contain a high level of hydrolases, resulting in rapid degradation of the internalized nanoparticles. There are four types of translocations: outer wrap, free translocate, inner attach and

Metabolism of nanomaterials

One of the most important features that have to be considered in the in vivo application of nanomaterials is their metabolism inside the body. Systemic distribution of nanomaterials inside the body is affected by 5 different clearance systems (Fig. 6A): a) the immune system contains different cells and proteins that can eliminate the nanoparticles from the body via a phenomenon known as the protein corona effect. The reticuloendothelial system, also known as the mononuclear phagocyte system, is

Biomedical applications

Non-spherical metal-based nanostructures such as rods, cubes and sheets have been employed in different sectors. This section deals with the application of shaped metal nanoarchitectures in the biomedical arena. Examples of these applications are biosensing, regenerative medicine, cancer diagnosis and therapy (Fig. 7).

Perspectives

Research and application of various shapes of nanomaterials in biomedicine have made great progress over the last decade. This is attributed primarily to the rapid development and integration between materials science and biomedical research. To date, applications of nanomaterials in medicine include cancer diagnosis and treatment, nerve regeneration, wound healing and bone regeneration. The characteristics of nanomedicines such as small size, strong activity and high specificity make it a most

Notes

The authors declare no competing financial interest.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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¹: These authors contributed equally to this work

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Applied Materials Today

Non-spherical nanostructures in nanomedicine: From noble metal nanorods to transition metal dichalcogenide nanosheets

Highlights

Abstract

Graphical abstract

Introduction

Section snippets

Preparation methods of non-spherical nanoparticles

Cellular uptake of nanomaterials

Endocytosis mechanisms

Effect of nanoparticle aspect ratio on cellular uptake

Interfacial interaction between nanoparticles and cells

Intracellular translocation

Metabolism of nanomaterials

Biomedical applications

Perspectives

Notes

Declaration of Competing Interest

Biomed. Appl., Elsevier

Biosens. Bioelectron.

J. Control. Release.

Biosens. Bioelectron.

J. Colloid Interface Sci.

Acta Biomater

Talanta

Electrochem. Commun.

Sep. Purif. Technol.

Biomaterials

Biochim. Biophys. Acta - Biomembr.

Arch. Biochem. Biophys.

J. Control. Release.

FEBS Lett

Curr. Opin. Cell Biol.

Cell

Toxicol. Appl. Pharmacol.

Toxicology

Curr. Opin. Microbiol.

Nanoscale Res. Lett.

Nano Today

Int. J. Pharm.

Acta Biomater

Metal-Based Nanomaterials in Biomedical Applications: Antimicrobial Activity and Cytotoxicity Aspects

Adv. Funct. Mater.

Metal-Based Nanostructures/PLGA Nanocomposites: Antimicrobial Activity, Cytotoxicity, and Their Biomedical Applications

ACS Appl. Mater. Interfaces.

Live-cell surface-enhanced Raman spectroscopy imaging of intracellular pH: From two dimensions to three dimensions

ACS Sensors

Smart Gold Nanostructures for Light Mediated Cancer Theranostics: Combining Optical Diagnostics with Photothermal Therapy

Adv. Sci.

Metal-Organic Framework Mediated Multifunctional Nanoplatforms for Cancer Therapy

Adv. Ther.

ZnO nanostructures for tissue engineering applications

Nanomaterials

Engineered Noble-Metal Nanostructures for in Vitro Diagnostics

Chem. Mater.

Complex-morphology metal-based nanostructures: Fabrication, characterization, and applications

Nanomaterials

Non-spherical micro- and nanoparticles in nanomedicine

Mater. Horizons.

Fabrication and Characterization of Non-spherical Polymeric Particles

J. Pharm. Innov.

Composite scaffolds of gelatin and gold nanoparticles with tunable size and shape for photothermal cancer therapy

J. Mater. Chem. B.

Shape induced inhibition of phagocytosis of polymer particles

Pharm. Res.

Shape effects of filaments versus spherical particles in flow and drug delivery

Proc. ASME Summer Bioeng. Conf. SBC2008

Solvent-Resistant Photocurable “Liquid Teflon” for Microfluidic Device Fabrication

J. Am. Chem. Soc.

Non-spherical micro- and nanoparticles: Fabrication, characterization and drug delivery applications

Expert Opin. Drug Deliv.

In-situ fabrication of threedimensional polymeric microstructures using soft membrane deformation and optofluidic maskless lithography

12th Int. Conf. Miniaturized Syst. Chem. Life Sci. - Proc. MicroTAS 2008 Conf.

Obtaining nonspherical poly(alkylcyanoacrylate) nanoparticles by the stretching method applied with a marketed water-soluble film

Int. J. Polym. Mater. Polym. Biomater.

Isolation of template effects that control the structure and function of nonspherical, biotemplated pd nanomaterials

Langmuir

Nonspherical noble metal nanoparticles: Colloid-chemical synthesis and morphology control

Adv. Mater.

Formation of Gold Nanorods by Seeded Growth: Mechanisms and Modeling