Ligand modified nanoparticles increases cell uptake, alters endocytosis and elevates glioma distribution and internalization

Gao, Huile; Liu, Yang; Zhang, Shuang; Cao, Sheng‐Li; Shen, Shun-Qing; Pang, Zhiqing; Jiang, Xinguo

doi:10.1038/srep02534

Cited by 272 publications

(208 citation statements)

References 42 publications

(55 reference statements)

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“…[50][51][52][53][54] Finally, as endocytosis of nanoparticles is an energy-dependent process, sodium azide (NaN 3 ) was used to deplete the energy demands for endocytosis and restrict metabolic activity. [62,63] FACS analysis revealed that Gen, Wor, and Noc had no adverse effect on the delivery of fluorescently labeled cytC (Figure 4a), whereas in the presence of Chl and NaN 3 , uptake of nanoparticles containing cytC was slightly lowered to 90% as compared to the initial experiment in the absence of inhibitors. To further study the role of CC formation on the mechanism of cellular uptake, we omitted the CP 4 K 4 pretreatment of HeLa cells in control experiments.…”

Section: Endocytosis and Micropinocytosis Inhibitors Marginally Affecmentioning

confidence: 91%

Membrane Fusion Mediated Intracellular Delivery of Lipid Bilayer Coated Mesoporous Silica Nanoparticles

Yang

Lamers

et al. 2017

Adv Healthcare Materials

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Protein delivery into the cytosol of cells is a challenging topic in the field of nanomedicine, because cellular uptake and endosomal escape are typically inefficient, hampering clinical applications. In this contribution cuboidal mesoporous silica nanoparticles (MSNs) containing disk‐shaped cavities with a large pore diameter (10 nm) are studied as a protein delivery vehicle using cytochrome‐c (cytC) as a model membrane‐impermeable protein. To ensure colloidal stability, the MSNs are coated with a fusogenic lipid bilayer (LB) and cellular uptake is induced by a complementary pair of coiled‐coil (CC) lipopeptides. Coiled‐coil induced membrane fusion leads to the efficient cytosolic delivery of cytC and triggers apoptosis of cells. Delivery of these LB coated MSNs in the presence of various endocytosis inhibitors strongly suggests that membrane fusion is the dominant mechanism of cellular uptake. This method is potentially a universal way for the efficient delivery of any type of inorganic nanoparticle or protein into cells mediated by CC induced membrane fusion.

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Section: Endocytosis and Micropinocytosis Inhibitors Marginally Affecmentioning

confidence: 91%

Membrane Fusion Mediated Intracellular Delivery of Lipid Bilayer Coated Mesoporous Silica Nanoparticles

Yang

Lamers

et al. 2017

Adv Healthcare Materials

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“…157 Therefore, we depleted the energy of the cortical neurons with sodium azide to inhibit endocytosis, an energy dependent process. 159 The addition of sodium azide reduced endocytosis of chitosan-coated MNPs by close to 90% but had no significant effects on starch-coated MNPs (Fig. 2b).…”

Section: Location and Uptake Of Mnpsmentioning

confidence: 99%

Acute and Chronic Neural Stimulation via Mechano-Sensitive Ion Channels

Tay

2018

Springer Theses

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Neural stimulation techniques for eliciting calcium influx can elucidate the physiological roles of specific neural populations. To overcome some of the limitations of existing techniques such as poor specificity and noxious effects of heat, I developed a technology for non-invasive control of neural activities using magnetic forces and magnetic nanoparticles (MNPs) which offer deep tissue penetration and controllable dosage. Extensive investigations with different neurotoxins and experimental conditions support that the mechanism of magnetic stimulation that involves membrane-bound MNPs transducing magnetic forces into mechanical stretching of the cell membrane to enhance the opening probability of mechano-sensitive N-type calcium ion channels to induce calcium influx.Making use of the ability of neural networks to actively regulate their ratio of excitatory to inhibitory ion channel/receptor, I also performed chronic magnetic stimulation on fragile X iii syndrome (FXS) model neural networks. We found that chronic magnetic stimulation reduced the density of N-type calcium ion channels whose expression is increased in FXS. This technique demonstrates the potential of using bio-magnetic/mechanical forces to modulate expressions of mechano-sensitive ion channels where they are over-expressed in diseases such as abnormal nociception.Nonetheless, there are still a few areas where the technique can be improved. Firstly, it is the use of MNPs with more uniform properties to have greater control on magnetic stimulations.Secondly, the technique needs to be useful for in vivo studies. Therefore, I started researching on magnetotactic bacteria (MTB) which produce biological MNPs with superior properties such as uniform sizes and highly homogenous magnetic properties with the goal of harvesting MNPs from them.MTB, however, grow extremely slowly and the number of MNPs produced/bacterium is low. One way to overcome this problem is to evolve MTB over-producers of MNPs but this strategy is constrained by the absence of a selection platform that is quantitative and offer high throughput. To overcome this problem, I combined random chemical mutagenesis and selection using a magnetic ratcheting platform to generate and isolate MTB over-producers that produce twice as many MNPs/bacterium after 5 rounds of mutation/selection. I next designed a magnetic microfluidic device and demonstrate as a proof of concept, that it can be coupled to a bioreactor for high throughput microfluidic selection of MTB over-producers.iv

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“…Nanocarriers have the capacity to enhance drug delivery by passive targeting due to the EPR effect in conjunction with their increased circulation half-life time. Several studies report that NPs are internalized into cancer cells through endocytosis ( Figure 6) [108,139,149]. Usually in biological environment serum proteins adsorb on NP surface facilitating the uptake mechanism by the formation of endocytic vesicles [139].…”

Section: Internalization Of Nanocarriersmentioning

confidence: 99%

“…Techniques such as transmission electron microscopy (TEM) and laser scanning confocal microscopy (LSCM) have been useful in understanding the mechanisms of NP uptake and toxicity [149,[151][152][153].…”

Section: Internalization Of Nanocarriersmentioning

confidence: 99%

Supramolecular nanoscale assemblies for cancer diagnosis and therapy

Coelho

Pereira

Juzeniene

et al. 2015

Journal of Controlled Release

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Nanocarriers based on polymers, metals and lipids have been extensively developed for cancer therapy and diagnosis due to their ability to enhance drug accumulation in cancer cells and decrease undesired drug toxicity in healthy tissues. Overcoming multidrug resistance by designing proper drug nanocarriers will improve outcome of existing oncologic treatments such as chemotherapy or radiotherapy. In this article the relation between physicochemical properties and capacity of a nanosystem to deliver therapeutic agents into pathological sites is discussed. Most promising examples of drug delivery systems are reviewed, and, in particular, the design of a carbohydrate based matrix with entrapped gold nanoparticles is highlighted.

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Ligand modified nanoparticles increases cell uptake, alters endocytosis and elevates glioma distribution and internalization

Cited by 272 publications

References 42 publications

Membrane Fusion Mediated Intracellular Delivery of Lipid Bilayer Coated Mesoporous Silica Nanoparticles

Membrane Fusion Mediated Intracellular Delivery of Lipid Bilayer Coated Mesoporous Silica Nanoparticles

Acute and Chronic Neural Stimulation via Mechano-Sensitive Ion Channels

Supramolecular nanoscale assemblies for cancer diagnosis and therapy

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