Effect of Physico-Chemical Properties of Nanoparticles on Their Intracellular Uptake

Abstract

Cellular internalization of inorganic, lipidic and polymeric nanoparticles is of great significance in the quest to develop effective formulations for the treatment of high morbidity rate diseases. Understanding nanoparticle–cell interactions plays a key role in therapeutic interventions, and it continues to be a topic of great interest to both chemists and biologists. The mechanistic evaluation of cellular uptake is quite complex and is continuously being aided by the design of nanocarriers with desired physico-chemical properties. The progress in biomedicine, including enhancing the rate of uptake by the cells, is being made through the development of structure–property relationships in nanoparticles. We summarize here investigations related to transport pathways through active and passive mechanisms, and the role played by physico-chemical properties of nanoparticles, including size, geometry or shape, core-corona structure, surface chemistry, ligand binding and mechanical effects, in influencing intracellular delivery. It is becoming clear that designing nanoparticles with specific surface composition, and engineered physical and mechanical characteristics, can facilitate their internalization more efficiently into the targeted cells, as well as enhance the rate of cellular uptake.

Differences in surface chemistry of iron oxide nanoparticles result in different routes of internalization

“…Once NPs enter biological fluids (blood or culture medium with serum), proteins immediately adsorb onto the surface of the NPs, forming a layer called protein corona (PC). The PC changes the surface composition and structure of NPs, directly influences the cell–NP interactions, determines the toxicity of NPs, and affects geometry and size of NPs, which play a crucial role in cellular uptake [ 38 – 39 ]. Despite nearly identical magnetite core size, hydrodynamic size, and zeta potential of the MNPs in the stock solution, the hydrodynamic size of PEG-SO-MNPs in culture medium was almost three times that of BSA-SO-MNPs (281 nm vs 98 nm, respectively) due to absorption of serum proteins on the particle surface [ 40 ].…”

Nanomaterials for Biomedical Applications: Production, Characterisations, Recent Trends and Difficulties

“…In the event that the diameter of spherical NPs is below 30 nm, they cannot drive the cell internalization. While those NPs over 60 nm can cause receptor saturation and strict hindrance to take place, the most optimum range of size is from 10 to 60 nm for higher cell uptake, without considering the surface charge and composition of the NPs [ 20 ]. However, utilising some bacterial species that produce carbohydrate secretions, which is a waste product, has appeared to assume a significant role in coordinating the molecular size and morphology of nanorods, alongside their production capacity.…”

“…Hyperthermia is a beneficial classical disease treatment, yet it is constrained by resistance of adjoining typical tissues. Parenteral organisation of gold nanorods (NRs) as a photosensitiser enhances the impacts of hyperthermia treatment, while saving typical tissues [20].The essential factor in fabricating NPs to internalise a cell layer is their size (Table 1), which can be in a very wide range in nanometres [20]. The NPs enter the cells through active or passive pathways, yet their size can impact the mechanisms of internalisation, medication release and immune reaction [20].…”

“…Parenteral organisation of gold nanorods (NRs) as a photosensitiser enhances the impacts of hyperthermia treatment, while saving typical tissues [20].The essential factor in fabricating NPs to internalise a cell layer is their size (Table 1), which can be in a very wide range in nanometres [20]. The NPs enter the cells through active or passive pathways, yet their size can impact the mechanisms of internalisation, medication release and immune reaction [20]. For instance, in all pathways of receptor-mediated endocytosis, activation of targeted cell receptors using specific ligands on the surface of the NPs is responsible for initiation of membrane wrapping.…”

Biomolecular interactions with nanoparticles: applications for coronavirus disease 2019

“…To ensure this happens efficiently, it is important that the NPs are correctly optimised to ensure maximum efficacy and correct bioavailability, as well as negating any toxic effects, particularly those related to the formation of reactive oxygen species (ROS) ( 5 ). Furthermore, the rate of cellular uptake of the NPs depends on their physicochemical properties and the membrane characteristics at the site of interaction ( 6 ).…”