Nontransformed and Cancer Cells Can Utilize Different Endocytic Pathways To Internalize Dendritic Nanoparticle Variants: Implications on Nanocarrier Design

Wong, Nelson K.Y.; Shenoi, Rajesh A.; Abbina, Srinivas; Chafeeva, Irina; Kizhakkedathu, Jayachandran N.; Khan, Mohamed K.

doi:10.1021/acs.biomac.7b00590

Cited by 20 publications

(8 citation statements)

References 46 publications

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“…30 Thus, we researched whether the cellular uptake of NP was influenced by the temperature. The cellular uptake of NP in the HepG2 cells incubated at 4°C was decreased ~74.1% (Figure S1), suggesting that the HA-Se-PEI@siRNA NP was internalized into the cells in an energy-dependent manner.…”

Section: Cellular Uptake Of Npmentioning

confidence: 99%

siRNA-loaded selenium nanoparticle modified with hyaluronic acid for enhanced hepatocellular carcinoma therapy

Xia¹,

Guo²,

Xu³

et al. 2018

IJN

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Background Small interfering RNA (siRNA) as a new therapeutic modality holds promise for cancer treatment. However, the traditional viral carriers are prone to immunogenicity and risk of insertional mutagenesis. Methods In order to provide a tumor-targeted delivery carrier of siRNA in cancer therapy, the hyaluronic acid (HA)-selenium (Se)-polyethylenimine (PEI) nanoparticle (NP) was fabricated by decorating SeNP with HA as a tumor-targeting moiety and by linking the polycationic polymers polyethylenimine PEI onto the surface of SeNP. The siRNA was loaded to the surface of SeNP HA-Se-PEI via the electrostatic interaction between siRNA and PEI to prepare the functionalized SeNP HA-Se-PEI@siRNA. Results The HA-Se-PEI@siRNA was internalized into the HepG2 cell mainly in a clathrin-mediated endocytosis manner. Owing to the active tumor-targeted effect mediated by HA, HA-Se-PEI@siRNA achieved the obvious higher transfection efficiency, greater gene silencing ability, and stronger cytotoxicity in the HepG2 cell compared with the passive tumor-targeted NP Se-PEI@siRNA. The knockdown of hairy and enhancer of split 5 by HA-Se-PEI@siRNA induced the HepG2 cell cycle arrest at the G0/G1 phase and apoptosis. Furthermore, the treatment with HA-Se-PEI@siRNA resulted in greater antitumor efficacy compared with the Se-PEI@siRNA in vitro and in vivo. In addition, the HA-Se-PEI@siRNA was almost no toxic to the key organs of mice. Conclusion These findings provided an alternative therapeutic route for targeted cancer treatments.

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Section: Cellular Uptake Of Npmentioning

confidence: 99%

siRNA-loaded selenium nanoparticle modified with hyaluronic acid for enhanced hepatocellular carcinoma therapy

Xia¹,

Guo²,

Xu³

et al. 2018

IJN

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“…To investigate the mechanism involved in the cellular uptake of DTNPs, we first incubated HeLa cells with 20 mm DTNPs at 4 8Cf or 2h.I nterestingly,t here was little difference in intracellular fluorescence compared with that at 37 8C, suggesting that the uptake of DTNPs was not energy-dependent ( Figure S16). We then pretreated HeLa cellswith different endocytosis inhibitors, such as chlorpromazine (CPZ), [20] Filipin III, [21] and 5-(Nethyl-N-isopropyl) amiloride (EIPA), [22] which also hadl ittle effect on the intracellular fluorescence( Figure S17). These results suggested that the intracellular delivery of DTNPs did not rely on the endocytosis/phagocytosis pathway.F urthermore, HPLC analysis of both culture medium and lysed HeLa cells following incubation with 20 mm DTNPsf or 2h showedt hat the majority of cationic DH-BBR + was taken up by HeLa cells, while the anionic TPB À wasd istributed mainly extracellularly ( Figure S18).…”

Section: Resultsmentioning

confidence: 99%

“…To investigate the mechanism involved in the cellular uptake of DTNPs, we first incubated HeLa cells with 20 μ m DTNPs at 4 °C for 2 h. Interestingly, there was little difference in intracellular fluorescence compared with that at 37 °C, suggesting that the uptake of DTNPs was not energy‐dependent (Figure S16). We then pretreated HeLa cells with different endocytosis inhibitors, such as chlorpromazine (CPZ), Filipin III, and 5‐( N ‐ethyl‐ N ‐isopropyl) amiloride (EIPA), which also had little effect on the intracellular fluorescence (Figure S17). These results suggested that the intracellular delivery of DTNPs did not rely on the endocytosis/phagocytosis pathway.…”

Section: Resultsmentioning

confidence: 99%

Self‐assembly of Fluorescent Dehydroberberine Enhances Mitochondria‐Dependent Antitumor Efficacy

Sun

et al. 2018

Chemistry A European J

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Selective imaging and inducing mitochondrial dysfunction in tumor cells using mitochondria-targeting probes has become as a promising approach for cancer diagnosis and therapy. Here, we report the design of a fluorescent berberine analog, dehydroberberine (DH-BBR), as a new mitochondria-targeting probe capable of self-assembling into monodisperse organic nanoparticles (DTNPs) upon integration with a lipophilic counter anion, allowing for enhanced fluorescence imaging and treatment of tumors in living mice. X-ray crystallography revealed that the self-assembly process was attributed to a synergy of different molecular interactions, including π-π stacking, O⋅⋅⋅π interaction and electrostatic interaction between DH-BBR and counter anions. We demonstrated that DTNPs could efficiently enter tumor tissue following intravenous injection and enhance mitochondrial delivery of DH-BBR via an electrostatic interaction driven anion exchange process. Selective accumulation in the mitochondria capable of emitting strong fluorescence and causing mitochondrial dysfunction was achieved, enabling efficient inhibition of tumor growth in living mice. This study demonstrates promise for applying lipophilic anions to control molecular self-assembly and tune antitumor activity of mitochondria-targeting probes, which can facilitate to improve cancer treatment in vivo.

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“…Gating of the live target cells was performed by selecting the main cell populations in the forward and side scatter profiles. Normalized mean florescence was computed by subtracting of the geometric mean florescence of the cells that were not incubated with any florescence labels [37].…”

Section: Methodsmentioning

confidence: 99%

Establishment and Expression of Cytokines in a Theileria annulata-Infected Bovine B Cell Line

Rashid

Guan

Luo

et al. 2019

Genes

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This study aimed to establish a pure single-cell Theileria annulata-infected B cell line for the assessment of cytokine production in transformed and lipopolysaccharide (LPS)-stimulated cells. Several studies have aimed to identify cell surface markers in T. annulata-transformed cells; however, no information on cytokine production in these cells is available. To investigate the potential of the transformed cells to produce cytokines and their potential responses to antigen-stimulation, we purified mature B cells (CD21) from the whole blood of cattle experimentally infected with the T. annulata Kashi strain by magnetic separation. The purity and specificity of the established cell line was assessed by the identification of specific cell surface markers (CD21, IgM, and WC4) by flow cytometry analysis. The transcript levels of the cytokines IL1A, IL1B, IL2, IL4, IL6, IL8, IL10, IL16, LTA, TGFB1, TNFA, IFNA, and IFNB in transformed, buparvaquone (BW720c)-treated cells, and antigen-stimulated cells were analyzed by quantitative polymerase chain reaction (qPCR) using cDNA from these cells. A T. annulata-infected bovine B cell line was successfully established with a purity of ~98.8% (CD21). IL4 and IL12A were significantly (p < 0.01) upregulated in the transformed cells. In BW720c-treated transformed cells, IL12B, TGFB1, and IFNB were significantly (p < 0.01) upregulated. Notably, no significant (p > 0.05) upregulation of cytokines was observed in LPS-stimulated transformed cells. Moreover, IL1A, IL1B, IL8, and IL16 were significantly (p < 0.01) upregulated in LPS-stimulated B cells. Our data signify the potential use of this cell line for cytokine production, observance of immunoglobulins, and production of an attenuated vaccine against tropical theileriosis.

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Nontransformed and Cancer Cells Can Utilize Different Endocytic Pathways To Internalize Dendritic Nanoparticle Variants: Implications on Nanocarrier Design

Cited by 20 publications

References 46 publications

siRNA-loaded selenium nanoparticle modified with hyaluronic acid for enhanced hepatocellular carcinoma therapy

siRNA-loaded selenium nanoparticle modified with hyaluronic acid for enhanced hepatocellular carcinoma therapy

Self‐assembly of Fluorescent Dehydroberberine Enhances Mitochondria‐Dependent Antitumor Efficacy

Establishment and Expression of Cytokines in a Theileria annulata-Infected Bovine B Cell Line

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