Insights into Cellular Uptake of Nanoparticles

Kafshgari, Morteza Hasanzadeh; Harding, Frances J.; Voelcker, Nicolas H.

doi:10.2174/1567201811666140821110631

Cited by 67 publications

(45 citation statements)

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“…35,36 For example, NP diameters of 50 nm, which are similar to the sizes of non-aggregated NP-siRNA here, are optimum for efficient uptake of multiple NP types across multiple cell lines 35 . Additionally, NPs with diameters similar to those used in this study are taken up via mechanisms that include clathrin- and caveolae-mediated endoctytosis and non-specific endocytosis 37,38 . In contrast, intracellular accumulation of aggregated NPs, with sizes of 200–400 nm, is observed with our studies as well, albeit at much lower frequencies.…”

Section: Resultsmentioning

confidence: 99%

The Effects of Biological Fluids on Colloidal Stability and siRNA Delivery of a pH-Responsive Micellar Nanoparticle Delivery System

et al. 2017

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Nanoparticles (NP) interact with complex protein milieus in biological fluids, and these interactions have profound effects on NP physicochemical properties and function. Surprisingly, most studies neglect the impact of these interactions, especially with respect to NP-mediated siRNA delivery. Here, the effects of serum on colloidal stability and siRNA delivery of a pH-responsive micellar NP delivery system were characterized. Results show cationic NP-siRNA complexes aggregate in ≥ 2% serum in buffer, but are stable in serum-free media. Furthermore, non-aggregated NP-siRNA delivered in serum-free media result in 4-fold greater siRNA uptake in vitro, compared to aggregated NP-siRNA. Interestingly, pH-responsive membrane lysis behavior, which is required for endosomal escape, and NP-siRNA dissociation, necessary for mRNA knockdown, are significantly reduced in serum. Consistent with these data, non-aggregated NP-siRNA in serum-free conditions result in highly efficient gene silencing, even at doses as low as 5 nM siRNA. NP-siRNA diameter was measured at albumin and IgG levels mimicking biological fluids. Neither albumin nor IgG alone induces NP-siRNA aggregation, implicating other serum proteins in NP colloidal instability. Finally, as a proof-of-principle that stability is maintained in established in vivo models, transmission electron microscopy reveals NP-siRNA are taken up by ductal epithelial cells in a non-aggregated state when injected retroductally into mouse salivary glands in vivo. Overall, this study shows serum-induced NP-siRNA aggregation significantly diminishes efficiency of siRNA delivery by reducing uptake, pH-responsive membrane lysis activity, and NP-siRNA dissociation. Moreover, these results highlight the importance of local NP-mediated drug delivery, and are broadly applicable to other drug delivery systems.

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Section: Resultsmentioning

confidence: 99%

The Effects of Biological Fluids on Colloidal Stability and siRNA Delivery of a pH-Responsive Micellar Nanoparticle Delivery System

et al. 2017

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“…If this scenario had occurred in the here presented study and interendothelial clefts were wide enough, residual nanoparticles in the blood would have been able to extravasate. Although MNPSNPs are negatively charged [96,97] and hydrophilic [98] due to PEG-coating, pinocytosis (< 500 nm size [99]) could occur, albeit more slowly. In addition, caveolae-mediated endocytosis which exists in muscles, among others [100], could have functioned as transcytosis pathway [101,102].…”

Section: Discussionmentioning

confidence: 99%

Biodistribution, biocompatibility and targeted accumulation of magnetic nanoporous silica nanoparticles as drug carrier in orthopedics

et al. 2020

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Background: In orthopedics, the treatment of implant-associated infections represents a high challenge. Especially, potent antibacterial effects at implant surfaces can only be achieved by the use of high doses of antibiotics, and still often fail. Drug-loaded magnetic nanoparticles are very promising for local selective therapy, enabling lower systemic antibiotic doses and reducing adverse side effects. The idea of the following study was the local accumulation of such nanoparticles by an externally applied magnetic field combined with a magnetizable implant. The examination of the biodistribution of the nanoparticles, their effective accumulation at the implant and possible adverse side effects were the focus. In a BALB/c mouse model (n = 50) ferritic steel 1.4521 and Ti90Al6V4 (control) implants were inserted subcutaneously at the hindlimbs. Afterwards, magnetic nanoporous silica nanoparticles (MNPSNPs), modified with rhodamine B isothiocyanate and polyethylene glycol-silane (PEG), were administered intravenously. Directly/1/7/21/42 day(s) after subsequent application of a magnetic field gradient produced by an electromagnet, the nanoparticle biodistribution was evaluated by smear samples, histology and multiphoton microscopy of organs. Additionally, a pathohistological examination was performed. Accumulation on and around implants was evaluated by droplet samples and histology.

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“…Among these pathways, the caveolae-mediated pathway mainly contributes to particles with diameters ,80 nm, as the caveolar endocytic vesicles are approximately 50-80 nm in diameter. 37,38 Therefore, clathrin-mediated endocytosis and phagocytosis were considered as potential mechanisms for the uptake of FITC-CsNPs by RAW 264.7 cells in this study.…”

Section: Uptake Pathwaymentioning

confidence: 99%

Intracellular disposition of chitosan nanoparticles in macrophages: intracellular uptake, exocytosis, and intercellular transport

Jiang¹,

Wang²,

Webster³

et al. 2017

IJN

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Biodegradable nanomaterials have been widely used in numerous medical fields. To further improve such efforts, this study focused on the intracellular disposition of chitosan nanoparticles (CsNPs) in macrophages, a primary cell of the mononuclear phagocyte system (MPS). Such interactions with the MPS determine the nanoparticle retention time in the body and consequently play a significant role in their own clinical safety. In this study, various dye-labeled CsNPs (about 250 nm) were prepared, and a murine macrophage cell line (RAW 264.7) was selected as a model macrophage. The results showed two mechanisms of macrophage incorporation of CsNPs, ie, a clathrin-mediated endocytosis pathway (the primary) and phagocytosis. Following internalization, the particles partly dissociated in the cells, indicating cellular digestion of the nanoparticles. It was proved that, after intracellular uptake, a large proportion of CsNPs were exocytosed within 24 h; this excretion induced a decrease in fluorescence intensity in cells by 69%, with the remaining particles possessing difficulty being cleared. Exocytosis could be inhibited by both wortmannin and vacuolin-1, indicating that CsNP uptake was mediated by lysosomal and multivesicular body pathways, and after exocytosis, the reuptake of CsNPs by neighboring cells was verified by further experiments. This study, thus, elucidated the fate of CsNPs in macrophages as well as identified cellular disposition mechanisms, providing the basis for how CsNPs are recognized by the MPS; such information is crucial to numerous medical applications of CsNPs.

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Insights into Cellular Uptake of Nanoparticles

Cited by 67 publications

References 0 publications

The Effects of Biological Fluids on Colloidal Stability and siRNA Delivery of a pH-Responsive Micellar Nanoparticle Delivery System

The Effects of Biological Fluids on Colloidal Stability and siRNA Delivery of a pH-Responsive Micellar Nanoparticle Delivery System

Biodistribution, biocompatibility and targeted accumulation of magnetic nanoporous silica nanoparticles as drug carrier in orthopedics

Intracellular disposition of chitosan nanoparticles in macrophages: intracellular uptake, exocytosis, and intercellular transport

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