Physicochemical properties determine nanomaterial cellular uptake, transport, and fate

Abstract

Although a growing number of innovations have emerged in the fields of nanobiotechnology and nanomedicine, new engineered nanomaterials (ENMs) with novel physicochemical properties are posing novel challenges to understand the full spectrum of interactions at the nano-bio interface. Because these could include potentially hazardous interactions, researchers need a comprehensive understanding of toxicological properties of nanomaterials and their safer design. In depth research is needed to understand how nanomaterial properties influence bioavailability, transport, fate, cellular uptake, and catalysis of injurious biological responses. Toxicity of ENMs differ with their size and surface properties, and those connections hold true across a spectrum of in vitro to in vivo nano-bio interfaces. In addition, the in vitro results provide a basis for modeling the biokinetics and in vivo behavior of ENMs. Nonetheless, we must use caution in interpreting in vitro toxicity results too literally because of dosimetry differences between in vitro and in vivo systems as well the increased complexity of an in vivo environment. In this Account, we describe the impact of ENM physicochemical properties on cellular bioprocessing based on the research performed in our groups. Organic, inorganic, and hybrid ENMs can be produced in various sizes, shapes and surface modifications and a range of tunable compositions that can be dynamically modified under different biological and environmental conditions. Accordingly, we cover how ENM chemical properties such as hydrophobicity and hydrophilicity, material composition, surface functionalization and charge, dispersal state, and adsorption of proteins on the surface determine ENM cellular uptake, intracellular biotransformation, and bioelimination versus bioaccumulation. We review how physical properties such as size, aspect ratio, and surface area of ENMs influence the interactions of these materials with biological systems, thereby affecting their hazard potential. We discuss our actual experimental findings and show how these properties can be tuned to control the uptake, biotransformation, fate, and hazard of ENMs. This Account provides specific information about ENM biological behavior and safety issues. This research also assists the development of safer nanotherapeutics and guides the design of new materials that can execute novel functions at the nano-bio interface.

Figure 1

Scheme of the main physicochemical properties govern the cellular process of ENMs which would be introduced in this Accounts. Other properties which were not elucidated in this Accounts but also involved in ENM cellular process were listed as other.

Figure 2

Biotransformation and fate of biodegradable, dissolvable and non-dissolved and non-biodegradable nanomaterials. (A) Modulating drugs release by PLGA-nanoparticles; (B) Dissolution difference between small size (23.5 nm) and big size (17 micron) copper nanoparticles in stomach of murine and in artificial acidic stomach fuild; (C) Dissolution of iron oxide nanoparticles by human monocytes; (D) Selective accumulation of Au nano-rods in cancer and normal cells result in distinct cytotoxicity. PLGA: poly (D,L-lactide-co-glycolide); PLA: polylactide; Cu: copper; CNTs: carbon nanotubes; TiO: titanium dioxide.

Figure 3

Natural size-rules and gatekeepers within a mammalian cell. The thickness of membrane bilayer is typically 4–10 nm. The nuclear pore complex (NPC) is approximately 80–120 nm in diameter. The sizes of endocytic vesicles in both phagocytosis and pinocytosis pathways for nanoparticles internalization were also introduced. Phagocytes could uptake large particles (or nanoparticle aggragates), opsonized nanoparticles, or nanoparticles with certain liagnds modification via phagocytosis. Nanoparticles internalization in non-phagocytic mammalian cell is mainly through pinocytosis or direct penetration. With different surface modifications, nanoparticles may be taken up via specific (receptor-mediated) endocytosis or non-specific endocytosis. The heterogeneity of nanoparticles suface and dispersion always take multiple uptake pathways involved. These natural size-restricted structures execute their barrier functions when nanoparticle comes in and out. Therefore, the convergence of spatial sizes indicates that the behaviors (uptake, transport and accumulation) of ENMs are restricted by the innate rules of biology. MR: mannose receptor; PRRs: pattern-recognition receptors, FcγR: immunoglobulin Fcγ receptor, CR: complement receptor, CPPs: cell penetrating peptide; IgG: immunoglobulin G, ER: endoplasmic reticulum; Golgi: Golgi apparatus

Figure 4

Impact of size and aspect ratio on ENMs cellular uptake. (A) Au nano-rods of different aspect ratio of 1.0 (CTAB-1), 2.0 (CTAB-2), 2.9 (CTAB-3) and 4.2 (CTAB-4), respectively. CTAB: cetyltrimethylammonium bromide; (B) Numbers of Au nano-rods within human breast adenocarcinoma (MCF-7) cells; (C) TEM image showing the process of cellular uptake of Au nano-rods. The Au nano-rods wrapping into vesicle and further get into lysosome; (D) Sketch map for how size and shape affect membrane wrapping kenetics in cell endocytosis. Changes in nanoparticle size may affect the surface ligand density, ligand conformation, surface curvature and relative orientation during nanoparticles membrane docking. Changes in nanoparticle aspect ratio may affect the position of surface ligand and wrapping time.