The endocytosis and intracellular fate of nanomedicines: Implication for rational design

Kou, Longfa; Sun, Jin; Zhai, Yinglei; Zhang, He

doi:10.1016/j.ajps.2013.07.001

Cited by 498 publications

(375 citation statements)

References 96 publications

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“…62 It was also established that positively charged nanoparticles can escape from endosomes after internalization, and they exhibit perinuclear localization because of the "proton sponge" effect. 63 …”

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confidence: 99%

Different patterns of nuclear and mitochondrial penetration by the G3 PAMAM dendrimer and its biotin–pyridoxal bioconjugate BC-PAMAM in normal and cancer cells in vitro

Uram¹,

Szuster²,

Filipowicz³

et al. 2015

IJN

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The intracellular localization and colocalization of a fluorescently labeled G3 amine-terminated cationic polyamidoamine (PAMAM) dendrimer and its biotin–pyridoxal (BC-PAMAM) bioconjugate were investigated in a concentration-dependent manner in normal human fibroblast (BJ) and squamous epithelial carcinoma (SCC-15) cell lines. After 24 hours treatment, both cell lines revealed different patterns of intracellular dendrimer accumulation depending on their cytotoxic effects. Cancer cells exhibited much higher (20-fold) tolerance for native PAMAM treatment than fibroblasts, whereas BC-PAMAM was significantly toxic only for fibroblasts at 50 µM concentration. Fibroblasts accumulated the native and bioconjugated dendrimers in a concentration-dependent manner at nontoxic range of concentration, with significantly lower bioconjugate loading. After reaching the cytotoxicity level, fluorescein isothiocyanate-PAMAM accumulation remains at high, comparable level. In cancer cells, native PAMAM loading at higher, but not cytotoxic concentrations, was kept at constant level with a sharp increase at toxic concentration. Mander’s coefficient calculated for fibroblasts and cancer cells confirmed more efficient native PAMAM penetration as compared to BC-PAMAM. Significant differences in nuclear dendrimer penetration were observed for both cell lines. In cancer cells, PAMAM signals amounted to ~25%–35% of the total nuclei area at all investigated concentrations, with lower level (15%–25%) observed for BC-PAMAM. In fibroblasts, the dendrimer nuclear signal amounted to 15% at nontoxic and up to 70% at toxic concentrations, whereas BC-PAMAM remained at a lower concentration-dependent level (0.3%–20%). Mitochondrial localization of PAMAM and BC-PAMAM revealed similar patterns in both cell lines, depending on the extracellular dendrimer concentration, and presented significantly lower signals from BC-PAMAM, which correlated well with the cytotoxicity.

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confidence: 99%

Different patterns of nuclear and mitochondrial penetration by the G3 PAMAM dendrimer and its biotin–pyridoxal bioconjugate BC-PAMAM in normal and cancer cells in vitro

Uram¹,

Szuster²,

Filipowicz³

et al. 2015

IJN

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“…68 The intracellular fate of nanoparticles is ultimately linked with the route of entry, which is dependent on the surface properties of the nanoparticles. 69 Endocytosis represents the major transport mechanism for nanomedicines across the membrane, including two major categories: phagocytosis, known as "cell eating", involving uptake of particles larger than 0.5 µm; and pinocytosis or "cell drinking" of fluid, solutes and suspensions containing small particles.…”

Section: Exploring Uptake Pathways Of Nanoparticlesmentioning

confidence: 99%

Preparation, in vitro and in vivo evaluation of polymeric nanoparticles based on hyaluronic acid-poly(butyl cyanoacrylate) and D-alpha-tocopheryl polyethylene glycol 1000 succinate for tumor-targeted delivery of morin hydrate

Abbad¹,

Wang²,

Waddad³

et al. 2015

IJN

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Herein, we describe the preparation of a targeted cellular delivery system for morin hydrate (MH), based on a low-molecular-weight hyaluronic acid-poly(butyl cyanoacrylate) (HA-PBCA) block copolymer. In order to enhance the therapeutic effect of MH, D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) was mixed with HA-PBCA during the preparation process. The MH-loaded HA-PBCA “plain” nanoparticle (MH-PNs) and HA-PBCA/TPGS “mixed” nanoparticles (MH-MNs) were concomitantly characterized in terms of loading efficiency, particle size, zeta potential, critical aggregation concentration, and morphology. The obtained MH-PNs and MH-MNs exhibited a spherical morphology with a negative zeta potential and a particle size less than 200 nm, favorable for drug targeting. Remarkably, the addition of TPGS resulted in about 1.6-fold increase in drug-loading. The in vitro cell viability experiment revealed that MH-MNs enhanced the cytotoxicity of MH in A549 cells compared with MH solution and MH-PNs. Furthermore, blank MNs containing TPGS exhibited selective cytotoxic effects against cancer cells without diminishing the viability of normal cells. In addition, the cellular uptake study indicated that MNs resulted in 2.28-fold higher cellular uptake than that of PNs, in A549 cells. The CD44 receptor competitive inhibition and the internalization pathway studies suggested that the internalization mechanism of the nanoparticles was mediated mainly by the CD44 receptors through a clathrin-dependent endocytic pathway. More importantly, MH-MNs exhibited a higher in vivo antitumor potency and induced more tumor cell apoptosis than did MH-PNs, following intravenous administration to S180 tumor-bearing mice. Overall, the results imply that the developed nanoparticles are promising vehicles for the targeted delivery of lipophilic anticancer drugs.

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“…However, this study did not evaluate the longer-term retention of particles of different magnetite content by the labeled cells, or establish the pattern of 'inheritance' of particles by daughter NSCs post-proliferation. Furthermore, it is well established that uptake of nanoparticles is mediated via a range of endocytotic mechanisms [9][10][11][12]. In this context, it should be noted that NSCs have relatively small cell bodies, elaborate limited amounts of cell membrane and appear in ultrastructural observations to possess comparatively quiescent membranes [13].…”

mentioning

confidence: 99%

Endocytotic Potential Governs Magnetic Particle Loading in Dividing Neural Cells: Studying Modes of Particle Inheritance

Tickle

Jenkins

Polyak

et al. 2016

Nanomedicine (Lond.)

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Aim: To achieve high and sustained magnetic particle loading in a proliferative and endocytotically active neural transplant population (astrocytes) through tailored magnetite content in polymeric iron oxide particles. Materials & methods: MPs of varying magnetite content were applied to primary-derived rat cortical astrocytes ± static/oscillating magnetic fields to assess labeling efficiency and safety. Results: Higher magnetite content particles display high but safe accumulation in astrocytes, with longer-term label retention versus lower/no magnetite content particles. Magnetic fields enhanced loading extent. Dynamic live cell imaging of dividing labeled astrocytes demonstrated that particle distribution into daughter cells is predominantly 'asymmetric'. Conclusion: These findings could inform protocols to achieve efficient MP loading into neural transplant cells, with significant implications for post-transplantation tracking/localization.

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The endocytosis and intracellular fate of nanomedicines: Implication for rational design

Cited by 498 publications

References 96 publications

Different patterns of nuclear and mitochondrial penetration by the G3 PAMAM dendrimer and its biotin–pyridoxal bioconjugate BC-PAMAM in normal and cancer cells in vitro

Different patterns of nuclear and mitochondrial penetration by the G3 PAMAM dendrimer and its biotin–pyridoxal bioconjugate BC-PAMAM in normal and cancer cells in vitro

Preparation, in vitro and in vivo evaluation of polymeric nanoparticles based on hyaluronic acid-poly(butyl cyanoacrylate) and D-alpha-tocopheryl polyethylene glycol 1000 succinate for tumor-targeted delivery of morin hydrate

Endocytotic Potential Governs Magnetic Particle Loading in Dividing Neural Cells: Studying Modes of Particle Inheritance

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The endocytosis and intracellular fate of nanomedicines: Implication for rational design

Cited by 498 publications

References 96 publications

Different patterns of nuclear and mitochondrial penetration by the G3 PAMAM dendrimer and its biotin&ndash;pyridoxal bioconjugate BC-PAMAM in normal and cancer cells in vitro

Different patterns of nuclear and mitochondrial penetration by the G3 PAMAM dendrimer and its biotin&ndash;pyridoxal bioconjugate BC-PAMAM in normal and cancer cells in vitro

Preparation, in vitro and in vivo evaluation of polymeric nanoparticles based on hyaluronic acid-poly(butyl cyanoacrylate) and D-alpha-tocopheryl polyethylene glycol 1000 succinate for tumor-targeted delivery of morin hydrate

Endocytotic Potential Governs Magnetic Particle Loading in Dividing Neural Cells: Studying Modes of Particle Inheritance

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Different patterns of nuclear and mitochondrial penetration by the G3 PAMAM dendrimer and its biotin–pyridoxal bioconjugate BC-PAMAM in normal and cancer cells in vitro

Different patterns of nuclear and mitochondrial penetration by the G3 PAMAM dendrimer and its biotin–pyridoxal bioconjugate BC-PAMAM in normal and cancer cells in vitro