Comparison of growth and drug response of human tumor cells in serum‐free and serum‐supplemented media in human tumor‐clonogenic assay

Zirvi, Karimullah A.; Hill, George J.

doi:10.1002/jso.2930380206

Cited by 3 publications

(1 citation statement)

References 15 publications

(6 reference statements)

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“…Our goal was to determine the effectiveness of the ammonium bicarbonate and doxorubicin coencapsulated liposomes when ultrasound is applied. Numerous literature reports demonstrate the efficacy of doxorubicin for PANC-1 cells (without the applied ultrasound); − hence, we did not include this control experiment.…”

Section: Resultsmentioning

confidence: 99%

pH-Triggered Echogenicity and Contents Release from Liposomes

et al. 2014

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Liposomes are representative lipid nanoparticles widely used for delivering anticancer drugs, DNA fragments, or siRNA to cancer cells. Upon targeting, various internal and external triggers have been used to increase the rate for contents release from the liposomes. Among the internal triggers, decreased pH within the cellular lysosomes has been successfully used to enhance the rate for releasing contents. However, imparting pH sensitivity to liposomes requires the synthesis of specialized lipids with structures that are substantially modified at a reduced pH. Herein, we report an alternative strategy to render liposomes pH sensitive by encapsulating a precursor which generates gas bubbles in situ in response to acidic pH. The disturbance created by the escaping gas bubbles leads to the rapid release of the encapsulated contents from the liposomes. Atomic force microscopic studies indicate that the liposomal structure is destroyed at a reduced pH. The gas bubbles also render the liposomes echogenic, allowing ultrasound imaging. To demonstrate the applicability of this strategy, we have successfully targeted doxorubicin-encapsulated liposomes to the pancreatic ductal carcinoma cells that overexpress the folate receptor on the surface. In response to the decreased pH in the lysosomes, the encapsulated anticancer drug is efficiently released. Contents released from these liposomes are further enhanced by the application of continuous wave ultrasound (1 MHz), resulting in substantially reduced viability for the pancreatic cancer cells (14%).

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Section: Resultsmentioning

confidence: 99%

pH-Triggered Echogenicity and Contents Release from Liposomes

et al. 2014

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Sensitivity of human colon tumor metastases to anticancer drugs in athymic (nude) mice

Zirvi¹,

Najjar²,

Slomiany³

1993

Cancer Letters

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CF₃ Derivatives of the Anticancer Ru(III) Complexes KP1019, NKP-1339, and Their Imidazole and Pyridine Analogues Show Enhanced Lipophilicity, Albumin Interactions, and Cytotoxicity

et al. 2016

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The Ru(III) complexes indazolium [trans-RuCl4(1H-indazole)2] (KP1019) and sodium [trans-RuCl4(1H-indazole)2] (NKP-1339) are leading candidates for the next generation of metal-based chemotherapeutics. Trifluoromethyl derivatives of these compounds and their imidazole and pyridine analogues were synthesized to probe the effect of ligand lipophilicity on the pharmacological properties of these types of complexes. Addition of CF3 groups also provided a spectroscopic handle for (19)F NMR studies of ligand exchange processes and protein interactions. The lipophilicities of the CF3-functionalized compounds and their unsubstituted parent complexes were quantified by the shake-flask method to give the distribution coefficient D at pH 7.4 (log D7.4). The solution behavior of the CF3-functionalized complexes was characterized in phosphate-buffered saline (PBS) using (19)F NMR, electron paramagnetic resonance (EPR), and UV-vis spectroscopies. These techniques, along with fluorescence competition experiments, were also used to characterize interactions with human serum albumin (HSA). From these studies it was determined that increased lipophilicity correlates with reduced solubility in PBS but enhancement of noncoordinate interactions with hydrophobic domains of HSA. These protein interactions improve the solubility of the complexes and inhibit the formation of oligomeric species. EPR measurements also demonstrated the formation of HSA-coordinated species with longer incubation. (19)F NMR spectra show that the trifluoromethyl complexes release axial ligands in PBS and in the presence of HSA. In vitro testing showed that the most lipophilic complexes had the greatest cytotoxic activity. Addition of CF3 groups enhances the activity of the indazole complex against A549 nonsmall cell lung carcinoma cells. Furthermore, in the case of the pyridine complexes, the parent compound was inactive against the HT-29 human colon carcinoma cell line but showed strong cytotoxicity with CF3 functionalization. Overall, these studies demonstrate that lipophilicity may be a determining factor in the anticancer activity and pharmacological behavior of these types of Ru(III) complexes.

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Comparison of growth and drug response of human tumor cells in serum‐free and serum‐supplemented media in human tumor‐clonogenic assay

Cited by 3 publications

References 15 publications

pH-Triggered Echogenicity and Contents Release from Liposomes

pH-Triggered Echogenicity and Contents Release from Liposomes

Sensitivity of human colon tumor metastases to anticancer drugs in athymic (nude) mice

CF₃ Derivatives of the Anticancer Ru(III) Complexes KP1019, NKP-1339, and Their Imidazole and Pyridine Analogues Show Enhanced Lipophilicity, Albumin Interactions, and Cytotoxicity

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Comparison of growth and drug response of human tumor cells in serum‐free and serum‐supplemented media in human tumor‐clonogenic assay

Cited by 3 publications

References 15 publications

pH-Triggered Echogenicity and Contents Release from Liposomes

pH-Triggered Echogenicity and Contents Release from Liposomes

Sensitivity of human colon tumor metastases to anticancer drugs in athymic (nude) mice

CF3 Derivatives of the Anticancer Ru(III) Complexes KP1019, NKP-1339, and Their Imidazole and Pyridine Analogues Show Enhanced Lipophilicity, Albumin Interactions, and Cytotoxicity

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CF₃ Derivatives of the Anticancer Ru(III) Complexes KP1019, NKP-1339, and Their Imidazole and Pyridine Analogues Show Enhanced Lipophilicity, Albumin Interactions, and Cytotoxicity