Effects of particle uptake, encapsulation, and localization in cancer cells on intracellular applications

Gal, Naama; Massalha, S.; Samuelly-Nafta, O.; Weihs, Daphne

doi:10.1016/j.medengphy.2015.03.003

Cited by 20 publications

(19 citation statements)

References 53 publications

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“…We hypothesized that the differences in the internalization of EVs between malignant and normal cells were related to differences in the endocytosis pathway involved [48]. Endocytosis occurs through two major mechanisms: phagocytosis and pinocytosis.…”

Section: Mechanism Of Cellular Uptake Of Evsmentioning

confidence: 99%

Cytotoxic Effects of Plant Sap-Derived Extracellular Vesicles on Various Tumor Cell Types

Kim

Yoo

Jung

et al. 2020

JFB

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Edible plants have been widely used in traditional therapeutics because of the biological activities of their natural ingredients, including anticancer, antioxidant, and anti-inflammatory properties. Plant sap contains such medicinal substances and their secondary metabolites provide unique chemical structures that contribute to their therapeutic efficacy. Plant extracts are known to contain a variety of extracellular vesicles (EVs) but the effects of such EVs on various cancers have not been investigated. Here, we extracted EVs from four plants—Dendropanax morbifera, Pinus densiflora, Thuja occidentalis, and Chamaecyparis obtusa—that are known to have cytotoxic effects. We evaluated the cytotoxic effects of these EVs by assessing their ability to selectively reduce the viability of various tumor cell types compared with normal cells and low metastatic cells. EVs from D. morbifera and P. densiflora sap showed strong cytotoxic effects on tumor cells, whereas those from T. occidentalis and C. obtusa had no significant effect on any tumor cell types. We also identified synergistic effect of EVs from D. morbifera and P. densiflora saps on breast and skin tumor cells and established optimized treatment concentrations. Our findings suggest these EVs from plant sap as new candidates for cancer treatment.

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Section: Mechanism Of Cellular Uptake Of Evsmentioning

confidence: 99%

Cytotoxic Effects of Plant Sap-Derived Extracellular Vesicles on Various Tumor Cell Types

Kim

Yoo

Jung

et al. 2020

JFB

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“…A higher change in fluorescence intensities was observed for MDA-MB-231 (metastatic breast cancer cell line) and MCF-7 (cancerous but non-metastatic breast cancer cell line) than the MCF-10A (normal breast cell line) (Bajaj et al 2009). Gal et al (2015) also reported differences in internalization of 200nm diameter particles in three types of breast cell lines. Accumulation of NPs was significantly higher in MDA-MB-231 (high metastatic potential) and MDA-MB-468 cells (low metastatic potential) compared to MCF-10A cells (benign).…”

Section: Resultsmentioning

confidence: 82%

“…Accumulation of NPs was significantly higher in MDA-MB-231 (high metastatic potential) and MDA-MB-468 cells (low metastatic potential) compared to MCF-10A cells (benign). This group suggested that the difference in accumulation is because normal cells form tight intra-connected colonies and therefore, NPs can be internalized mostly only at the edge of a growing colony, while in malignant cells, the cell-cell and the cell-matrix connection is disturbed and therefore, NPs can be internalized into any cell on the tissue culture plate (Gal et al 2015).…”

Section: Resultsmentioning

confidence: 99%

Gold nanoparticle mediated combined cancer therapy

et al. 2018

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Background: The combined use of radiation therapy and chemotherapy is commonly being used in cancer treatment. The side effects of the treatment can be further minimized through targeted delivery of anticancer drugs and local enhancement of the radiation dose. Gold nanoparticles (GNPs) can play a significant role in this regard since GNPs can be used as radiation dose enhancers and anticancer drug carriers. Anticancer drug, bleomycin, was chosen as the model drug, since it could be easily conjugated onto GNPs through the gold-thiol bond. Methods: Gold nanoparticles of size 10 nm were synthesized using the citrate reduction method. The surface of The GNPs was modified with a peptide sequence (CKKKK-KKGGRGDMFG) containing the RGD domain and anticancer drug, bleomycin. Human breast cancer cells (MDA-MB-231) were incubated with 0.3 nM concentration of GNPdrug complex for 16 h prior to irradiation with a 2 Gy single fraction of 6 MV X-rays. After the treatment, cells were trypsinized and seeded in 60 mm dishes for clonogenic assay. Damage to DNA was probed using immunofluorescence assay. Results: Cancer cells internalized with the GNP-drug complex had a 32 ± 9% decrease in cell survival and statistically significant enhancement in DNA (deoxyribonucleic acid) damage as compared to control cells (irradiated with no GNPs) after receiving a radiation dose of 2 Gy with 6 MV photons. Conclusions: The experimental results demonstrate that GNP-mediated chemoradiation has the potential to improve cancer care in the near future through enhancement of the local radiation dose and controlled delivery of anticancer drugs.

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“…For example, the two cell lines might have differing rates of endocytosis, which could influence the extent of intracellular uptake of the nanoprobes, leading to differences in fluorescence intensities that are not completely caused by the enzymatic activation of the nanoprobes. The dependence of endocytic rates on fluorescent agent or nanoparticle identity, time of exposure, and cell line has been previously reported for benign and malignant cell lines of different metastatic potential . For this reason, additional studies were conducted with MDA‐MB‐231 breast cancer cells to study the effect of enzymatic activity on fluorescence development.…”

Section: Resultsmentioning

confidence: 95%

Enzymatically activated near infrared nanoprobes based on amphiphilic block copolymers for optical detection of cancer

et al. 2015

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Background and Objective Nanotechnology offers the possibility of creating multi-functional structures that can provide solutions for biomedical problems. The nanoprobes herein described are an example of such structures, where nanoprobes have been designed to provide high specificity and contrast potential for optical detection of cancer. Specifically, enzymatically activated fluorescent nanoprobes (EANPs) were synthesized as cancer-specific contrast agents for optical imaging. Study Design/Materials and Methods EANPs were prepared by nanoprecipitation of blends of poly(lactic acid)-b-poly(ethylene glycol) and poly(lactic-co-glycolic acid)-b-poly(L-lysine). The lysine moieties were then covalently decorated with the near infrared (NIR) fluorescent molecule AlexaFluor-750 (AF750). Close proximity of the fluorescent molecules to each other resulted in fluorescence quenching, which was be reversed by enzymatically mediated cleavage of poly(L-lysine) chains. EANPs were characterized by dynamic light scattering and electron microscopy. Enzymatic development of fluorescence was studied in vitro by fluorescence spectroscopy. Biocompatibility and contrast potential of EANPs were studied in cancerous and noncancerous cells. The potential of the nanoprobes as contrast agents for NIR fluorescence imaging was studied in tissue phantoms. Results Spherical EANPs of ∼100 nm were synthesized via nanoprecipitation of polymer blends. Fluorescence activation of EANPs by treatment with a model protease was demonstrated with up to 15-fold optical signal enhancement within 120 minutes. Studies with MDA-MB-231 breast cancer cells demonstrated the cytocompatibility of EANPs, as well as enhanced fluorescence associated with enzymatic activation. Imaging studies in tissue phantoms confirmed the ability of a simple imaging system based on a laser source and CCD camera to image dilute suspensions of the nanoprobe at depths of up to 4 mm, as well as up to a 13-fold signal-to-background ratio for enzymatically activated EANPs compared to un-activated EANPs at the same concentration. Conclusion Nanoprecipitation of copolymer blends containing poly(L-lysine) was utilized as a method for preparation of highly functional nanoprobes with high potential as contrast agents for fluorescence based imaging of cancer.

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Effects of particle uptake, encapsulation, and localization in cancer cells on intracellular applications

Cited by 20 publications

References 53 publications

Cytotoxic Effects of Plant Sap-Derived Extracellular Vesicles on Various Tumor Cell Types

Cytotoxic Effects of Plant Sap-Derived Extracellular Vesicles on Various Tumor Cell Types

Gold nanoparticle mediated combined cancer therapy

Enzymatically activated near infrared nanoprobes based on amphiphilic block copolymers for optical detection of cancer

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