Abstract
Several challenges exist for successful nanoparticle cellular uptake—they must be able to cross many physical barriers to reach their target and overcome the cell membrane. A strategy to overcome this challenge is to exploit natural uptake mechanisms namely passive and endocytic (i.e., clathrin- and caveolin-dependent/-independent endocytosis, macropinocytosis and phagocytosis). The influence of nanoparticle material and size is well documented and understood compared to the influence of nanomaterial shape. Generally, nanoparticle shape is referred to as being either spherical or non-spherical and is known to be an important factor in many processes. Nanoparticle shape-dependent effects in areas such as immune response, cancer drug delivery, theranostics and overall implications for nanomedicines are of great interest. Studies have looked at the cellular uptake of spherical NPs, however, fewer in comparison have investigated the cellular uptake of non-spherical NPs. This review explores the exploitation of endocytic pathways for mainly inorganic non-spherical (shapes of focus include rod, triangular, star-shaped and nanospiked) nanoparticles cellular uptake. The role of mathematical modelling as predictive tools for non-spherical nanoparticle cellular uptake is also reviewed. Both quantitative structure-activity relationship (QSAR) and continuum membrane modelling have been used to gain greater insight into the cellular uptake of complex non-spherical NPs at a greater depth difficult to achieve using experimental methods.
Highlights
Academic Editor: Mikhael BechelanyNanoparticles (NPs), i.e., particles from 1 to 100 nm [1] can be engineered in a multitude of ways to give different sizes, shapes, and surface chemistries for a variety of applications ranging from energy production, industrial production processes, pharmaceutical and biomedical applications [2]
Clathrin-dependent endocytosis (Figure 1) begins via the attachment of nanoparticle ligands to cell membrane receptors, e.g., epidermal growth factor (EGF) receptors. clathrindependent endocytosis involves many steps; the first being the formation of a pit coated with clathrin protein consisting of the receptor-bound NPs within the pit; this is followed by cell membrane invagination and the breaking-off of the cell membrane invagination to form an intracellular vesicle
This review explored the behaviours of non-spherical NPs namely rod, triangular, star-shaped and nanospiked as they related to specific endocytic cellular uptake mechanisms
Summary
Nanoparticles (NPs), i.e., particles from 1 to 100 nm (though some are larger than. 100 nm) [1] can be engineered in a multitude of ways to give different sizes, shapes, and surface chemistries for a variety of applications ranging from energy production, industrial production processes, pharmaceutical and biomedical applications [2]. Membrane fusion mechanisms occur when two lipid membranes combine to form one continuous bilayer resulting in lipid mixing and cellular content transfer [5] This process is highly regulated involving several functional proteins such as soluble N-ethylmaleimide attachment protein receptor (SNARE) proteins and is a functional entry route for nanomedicines (e.g., content transfer via liposome-liposome fusion) [5]. The recent review by Kapate et al 2021 provides a compressive review on the role (cell-particle interactions, particle transport, distribution and immune response) of non-spherical NPs in drug delivery and progress made in the last 15 years [21]. The specific objectives of this review are first, to explore the behaviours of (mainly inorganic) non-spherical NPs on specific endocytic cellular mechanisms namely clathrin and caveolin dependent and independent endocytosis, phagocytosis and macropinocytosis. To highlight the role of predictive mathematical modelling such as quantitative structure-activity (QSAR) and continuum membrane modelling which have proven useful in investigating the influence of nonspherical NPs on cellular entry and uptake at a greater depth difficult to achieve using experimental methods [22,23]
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