Gold nanoparticles impair autophagy flux through shape-dependent endocytosis and lysosomal dysfunction

2018 ◽  
Vol 6 (48) ◽  
pp. 8127-8136 ◽  
Author(s):  
Hualu Zhou ◽  
Xuanqing Gong ◽  
Hongyu Lin ◽  
Hongming Chen ◽  
Dengtong Huang ◽  
...  

Gold nanospheres stimulate more autophagosome accumulation than gold nanorods due to their higher efficiency of cellular uptake.

2016 ◽  
Vol 8 (1) ◽  
Author(s):  
Jyoti Verma ◽  
Henk A. Van Veen ◽  
Sumit Lal ◽  
Cornelis J.F. Van Noorden

AbstractNanoparticles with coating entrapping a chemotherapeutic drug for delivery have not been tested for their cytotoxic effects in in-vitro glioblastoma cell cultures to increase treatment efficacy. Therefore, we synthesized silica-coated gold nanorods and gold nanospheres that were loaded with doxorubicin or temozolomide. The morphology of the nanoparticles was characterized using transmission electron microscopy (TEM), the molecular structure was characterized using infrared spectroscopy and in vitro efficacy was determined using glioblastoma cell cultures. TEM analysis showed that gold nanorods had a length of 49–65 nm and a diameter of 8.5–14 nm whereas gold nanospheres had a diameter of 9.5–37 nm. Infrared spectroscopy of doxorubicin and temozolomide and the silica coating revealed molecular fingerprints such as bending, stretching and vibrations of chemical bonds that confirmed the presence of silica coating and drug loading of the gold nanoparticles. In the biological assessment of the effects of drug-loaded gold nanoparticles on primary glioblastoma cell cultures, cytotoxicity, viability and the ratio of cyototoxicity and viability were used as parameters to analyze the effects on the cells of drug delivery via gold nanoparticles on the cells. Our data suggest that doxorubicin in the concentration range of 0.12–3.16 μM when delivered using both gold nanorods and nanospheres induced a 3.8–5.5-fold increased cytotoxicity in comparison to direct delivery. Temozolomide in the concentration range of 4.6–115 μM when delivered by either type of gold nanoparticles induced a 2–4-fold increased cytotoxicity in comparison to direct delivery. Nanospheres were more effective in delivery and cytotoxicity of doxorubicin and temozolomide to glioblastoma cells than gold nanorods. Our data suggest that gold nanoparticles and in particular gold nanospheres are more effective in delivery of doxorubicin and temozolomide to primary glioblastoma cells in culture than direct delivery.


2018 ◽  
Vol 6 (16) ◽  
pp. 2432-2443 ◽  
Author(s):  
J. Ruff ◽  
N. Hassan ◽  
F. Morales-Zavala ◽  
J. Steitz ◽  
E. Araya ◽  
...  

Gold nanoparticles with specific optical properties in combination with the CLPFFD peptide that exhibits selectivity for β-amyloid (Aβ) aggregates are promising photothermal absorbers for application in Alzheimer's disease therapy.


2016 ◽  
Vol 33 (9) ◽  
pp. 698-702 ◽  
Author(s):  
Ziyin Fan ◽  
Moritz Tebbe ◽  
Andreas Fery ◽  
Seema Agarwal ◽  
Andreas Greiner

2015 ◽  
Vol 25 (22) ◽  
pp. 3433-3439 ◽  
Author(s):  
Zhiyue Zhang ◽  
Katleen Van Steendam ◽  
Samarendra Maji ◽  
Lieve Balcaen ◽  
Yulia Anoshkina ◽  
...  

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Vasanthy Narayanaswami ◽  
Skylar T Chuang ◽  
Young-Seok Shon

We have developed a novel HDL-based multifunctional platform for transport and delivery of highly hydrophobic gold nanoparticles (AuNP) bearing photothermic properties. We exploit the ability of apolipoprotein E3 (apoE3) to act as a high affinity ligand for the low-density lipoprotein receptor (LDLr) to gain entry into glioblastoma cells. The issue of poor aqueous solubility of AuNP was overcome by integrating them with phospholipids and apoE3, yielding reconstituted rHDL bearing 3, 10, or 10 nm AuNP. UV-Vis spectra of rHDL-AuNP indicated the presence of stable particles with surface plasmon band at ~530 nm, a signature feature of AuNP. Transmission electron microscopy (TEM) revealed discoidal geometry for rHDL with 3, 10 and 17 nm particles. Co-immunoprecipitation assay using a soluble form of the LDLr indicated robust binding of rHDL-AuNP to the receptor. Immunofluorescence analysis indicated that all 3 rHDL particles were internalized by glioblastoma cells, as revealed by the presence of punctate, peri-nuclear endocytic/lysosomal vesicles; this suggests cellular uptake of rHDL-AuNP by receptor-mediated endocytosis. Cellular uptake was further confirmed by TEM, in which aggregated AuNP were found in the endosomal-lysosomal compartments. Finally, cytotoxicity studies demonstrated that more than 50% of cells were viable with rHDL-AuNP treatment of up to 0.1 mg/ml for 24 h. The findings that apoE3: (i) acts as a detergent in solubilizing and dramatically improving the aqueous solubility of AuNP, and, (ii) facilitates cellular uptake of rHDL-AuNP by the LDLr pathway, are significant since they offer an effective means of delivering AuNP across the cell membrane. This is particularly relevant in tumor cells since they overexpress LDLr to meet the high demand for cholesterol that is required for rapid proliferation and membrane biogenesis.


2017 ◽  
Vol 494 (1-2) ◽  
pp. 339-345 ◽  
Author(s):  
Bo He ◽  
Dan Yang ◽  
Mengmeng Qin ◽  
Yuan Zhang ◽  
Bing He ◽  
...  

2017 ◽  
Vol 91 ◽  
pp. 123-133 ◽  
Author(s):  
Suhana Ahmad ◽  
Anes Ateqah Zamry ◽  
Hern-Tze Tina Tan ◽  
Kah Keng Wong ◽  
JitKang Lim ◽  
...  

2019 ◽  
Vol 1052 ◽  
pp. 1-9 ◽  
Author(s):  
Magdalena Matczuk ◽  
Lena Ruzik ◽  
Svetlana S. Aleksenko ◽  
Bernhard K. Keppler ◽  
Maciej Jarosz ◽  
...  

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