Abstract
Nanoparticles (NPs) have attracted considerable attention in various fields, such as cosmetics, the food industry, material design, and nanomedicine. In particular, the fast-moving field of nanomedicine takes advantage of features of NPs for the detection and treatment of different types of cancer, fibrosis, inflammation, arthritis as well as neurodegenerative and gastrointestinal diseases. To this end, a detailed understanding of the NP uptake mechanisms by cells and intracellular localization is essential for safe and efficient therapeutic applications. In the first part of this review, we describe the several endocytic pathways involved in the internalization of NPs and we discuss the impact of the physicochemical properties of NPs on this process. In addition, the potential challenges of using various inhibitors, endocytic markers and genetic approaches to study endocytosis are addressed along with the principal (semi) quantification methods of NP uptake. The second part focuses on synthetic and bio-inspired substances, which can stimulate or decrease the cellular uptake of NPs. This approach could be interesting in nanomedicine where a high accumulation of drugs in the target cells is desirable and clearance by immune cells is to be avoided. This review contributes to an improved understanding of NP endocytic pathways and reveals potential substances, which can be used in nanomedicine to improve NP delivery.
Highlights
Understanding nanoparticle endocytosis to improve targeting strategies in nanomedicine Mauro Sousa de Almeida, †a Eva Susnik, †a Barbara Drasler, a Patricia Taladriz-Blanco, a Alke Petri-Fink ab and Barbara Rothen-Rutishauser *a
In the first part of this review, we describe the several endocytic pathways involved in the internalization of NPs and we discuss the impact of the physicochemical properties of NPs on this process
It is crucial to understand their interactions with different cell types as well as their behaviour in the in vivo system in the presence of various molecules
Summary
Focuses on the design, production, and application of nanosized systems (e.g., devices, paints, food additives, and drug delivery systems).[1]. It is still challenging to generalize the current findings, due to the variation on the endocytic mechanisms dependent on cell types and for different NPs.[14,15,16,17] In addition, when NPs interact with physiological fluids such as mucus, lymph fluid, or blood, they can interact with different biomolecules including opsonins that promote cellular recognition and clearance by the mononuclear phagocyte system (MPS).[18] the presence of efflux pumps, overexpression of specific transporters on the cell membrane, as well as mitosis can reduce NP accumulation in the target cells.[19,20] a very low number of NPs reach the target cells and might not be sufficient to treat the disease.[21] For this reason, it becomes important to enhance NP-based targeted delivery and, at the same time, avoid internalization by MPS if this system is not the targeted one Various stimuli, such as inflammatory cytokines,[22] multiple NP co-exposure,[23,24] or functionalization with ligands[25,26,27] were described to increase NP uptake in target cells. A description of the different endocytic mechanisms is included together with the approaches for NP quantification
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