Size-dependent internalisation of folate-decorated nanoparticles via the pathways of clathrin and caveolae-mediated endocytosis in ARPE-19 cells

Suen, Wai Leung Langston; Chau, Ying

doi:10.1111/jphp.12134

Cited by 136 publications

(102 citation statements)

References 24 publications

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“…It has been reported that smaller nanoparticles undergo endocytic uptake by cells more easily and rapidly than larger one. 41,42) These previous observations are in accordance with our present results.…”

Section: Discussionsupporting

confidence: 83%

Influence of Physicochemical Properties and PEG Modification of Magnetic Liposomes on Their Interaction with Intestinal Epithelial Caco-2 Cells

Kono

Jinzai

Kotera

et al. 2017

Biological & Pharmaceutical Bulletin

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The present study aimed to investigate the effect of particle size (100, 500 nm), surface charge (cationic, neutral and anionic) and polyethylene glycol (PEG) modification of magnetic liposomes on their interaction with the human intestinal epithelial cell line, Caco-2. The cellular associated amount of all the magnetic liposomes was significantly increased by the presence of a magnetic field. The highest association and internalization into Caco-2 cells was observed with magnetic cationic liposomes. Moreover, small magnetic liposomes were more efficiently associated and taken up into the cells, than large ones. In contrast, PEG modification significantly attenuated the enhancing effect of the magnetic field on the cellular association of magnetic liposomes. We also found that magnetic cationic liposomes had the highest retention properties to Caco-2 cells. Moreover, the retention of large magnetic liposomes to the cells was much longer than that of small ones. In addition, magnetic cationic and neutral liposomes had relatively high stability in Caco-2 cells, whereas magnetic anionic liposomes rapidly degraded. These results indicate that the physicochemical properties and PEG modification of magnetic liposomes greatly influences their intestinal epithelial transport.

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Section: Discussionsupporting

confidence: 83%

Influence of Physicochemical Properties and PEG Modification of Magnetic Liposomes on Their Interaction with Intestinal Epithelial Caco-2 Cells

Kono

Jinzai

Kotera

et al. 2017

Biological & Pharmaceutical Bulletin

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“…However, 250 nm nanoparticles, were only internalized via caveolae-mediated pathway [35], despite some articles have described an upper limit size of ~150 nm for passage through caveolae vesicles [36]. …”

Section: Resultsmentioning

confidence: 99%

Intracellular trafficking and cellular uptake mechanism of PHBV nanoparticles for targeted delivery in epithelial cell lines

et al. 2017

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BackgroundNanotechnology is a science that involves imaging, measurement, modeling and a manipulation of matter at the nanometric scale. One application of this technology is drug delivery systems based on nanoparticles obtained from natural or synthetic sources. An example of these systems is synthetized from poly(3-hydroxybutyrate-co-3-hydroxyvalerate), which is a biodegradable, biocompatible and a low production cost polymer. The aim of this work was to investigate the uptake mechanism of PHBV nanoparticles in two different epithelial cell lines (HeLa and SKOV-3).ResultsAs a first step, we characterized size, shape and surface charge of nanoparticles using dynamic light scattering and transmission electron microscopy. Intracellular incorporation was evaluated through flow cytometry and fluorescence microscopy using intracellular markers. We concluded that cellular uptake mechanism is carried out in a time, concentration and energy dependent way. Our results showed that nanoparticle uptake displays a cell-specific pattern, since we have observed different colocalization in two different cell lines. In HeLa (Cervical cancer cells) this process may occur via classical endocytosis pathway and some internalization via caveolin-dependent was also observed, whereas in SKOV-3 (Ovarian cancer cells) these patterns were not observed. Rearrangement of actin filaments showed differential nanoparticle internalization patterns for HeLa and SKOV-3. Additionally, final fate of nanoparticles was also determined, showing that in both cell lines, nanoparticles ended up in lysosomes but at different times, where they are finally degraded, thereby releasing their contents.ConclusionsOur results, provide novel insight about PHBV nanoparticles internalization suggesting that for develop a proper drug delivery system is critical understand the uptake mechanism.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-016-0241-6) contains supplementary material, which is available to authorized users.

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“…It seems that the internalization of folate-decorated NPs is a size-dependent phenomena medicated via either clathrin-coated pits or caveolae-mediated endocytosis [57]. For example, NPs with size range about 50 nm appear to internalize quickly selectively through the clathrin-mediated endocytosis, while the internalization of NPs with size range at ~250 nm seems to be a slow process via the caveolae-mediated endocytosis as a dominant path.…”

Section: Discussionmentioning

confidence: 99%

Multifunctional mitoxantrone-conjugated magnetic nanosystem for targeted therapy of folate receptor-overexpressing malignant cells

Barar¹,

Kafil²,

Majd³

et al. 2016

Nano Online

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Principally, breast cancer treatment modalities are based on surgery, radiotherapy, hormone-therapy and chemotherapy [ 2]. Of these treatment modalities, chemotherapy agents are used to induce cytotoxic impacts in cancerous cells through various mechanisms such as DNA detriments and inhibition of cell division and growth. For instance, MTX as one of the chemotherapeutic agents is commonly used for the treatment of metastatic breast cancer, acute myeloid leukemia and non-Hodgkin's lymphoma. It hinders cell proliferation through inhibition of topoisomerase II and disruption of DNA repair/synthesis [3], intercalation of DNA [4], DNA damage and apoptosis via inhibition of the mitochondrial pathway [5]. Unfortunately, administration of MTX is associated with inevitable initiation of inadvertent side effects (e.g. weakness, hair loss, diarrhea, heart problems and immunosuppression), mainly because of the non-specific effects on the healthy cells/tissue [6,7]. Further, cancer cells may become resistant to MTX. To tackle such dilemmas, cancer cells must be targeted with smart drug delivery nanosystems (NSs) to deliver anticancer agents such as MTX specifically into the tumor microenvironment (TME) and hence malignant cells.Among various NSs (e.g., nanoliposomes, polymeric NPs, dendrimers and other organic/inorganic NPs) designed for targeted therapy of cancer [ 8], MNPs appear to be one of the most promising delivery agents because they are biocompatible and can be easily decorated with homing and therapy agents [9]. Besides, potent toxic agents conjugated onto MNPs can be localized at the target site using an external magnetic field [10]. Targeted MNPs were shown to accumulate highly within the target tumor cells through passive and active targeting mechanisms while use of an external magnetic field can intensify the accumulation of MNPs [11][12][13]. Of various oncomarkers exploited for targeted therapy of cancer, folate receptors (FRs) have highly been overexpressed in various solid tumors such as breast and ovarian cancers [14,15]. Hence, FA, a safe small molecule also known as vitamin M or B9, has been used as homing device to target the FRs-overexpressing malignant cells. Owing to its versatility and conjugation simplicity, the FA-conjugation have been used for engineering multimodal nanomedicines and theranostics [16][17][18][19]. Surface modification of MNPs with polyethylene glycol (PEG) was shown to enhance the biocompatibility and the duration of blood circulation and to reduce the antigenicity of MNPs [20,21]. For example, Zhang et al. coated MNPs with PEG-FA and reported increased internalization of the modified MNPs in BT20 cells with decreased uptake in macrophages [22]. We have previously engineered multimodal PEGylated MNPs armed with FA and conjugated with MTX [23], or loaded with tamoxifen (TMX) [ 24]. We have also capitalized on functionalized MNPs to enhance the delivery of plasmid DNA into Escherichia coli [25]. In the current study, we aimed to study the cytotoxicity mechanism(s) of the PEGylated ...

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Size-dependent internalisation of folate-decorated nanoparticles via the pathways of clathrin and caveolae-mediated endocytosis in ARPE-19 cells

Cited by 136 publications

References 24 publications

Influence of Physicochemical Properties and PEG Modification of Magnetic Liposomes on Their Interaction with Intestinal Epithelial Caco-2 Cells

Influence of Physicochemical Properties and PEG Modification of Magnetic Liposomes on Their Interaction with Intestinal Epithelial Caco-2 Cells

Intracellular trafficking and cellular uptake mechanism of PHBV nanoparticles for targeted delivery in epithelial cell lines

Multifunctional mitoxantrone-conjugated magnetic nanosystem for targeted therapy of folate receptor-overexpressing malignant cells

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