Effective Oral Administration of an Antitumorigenic Nanoformulated Titanium Complex

Gilad Nahari; Ori Braitbard; Liraz Larush; Jacob Hochman; Edit Y. Tshuva

doi:10.1002/cmdc.202000384

Effective Oral Administration of an Antitumorigenic Nanoformulated Titanium Complex

Gilad Nahari, Ori Braitbard, Liraz Larush, Jacob Hochman^*, Edit Y. Tshuva^*

^*Corresponding author for this work

Institute of Chemistry

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

Abstract: Orally administered anticancer drugs facilitate treatment, but the acidic conditions in the stomach often challenge their availability. PhenolaTi is a Ti^IV-based nontoxic anticancer drug with marked in-vivo efficacy. We report that nanoformulation protects phenolaTi from decomposition in stomach-like conditions. This is evidenced by similar NMR characteristics and similar in-vitro cytotoxicity toward murine (CT-26) and human (HT-29) colon cancer cells before and after incubation of nanoformulated phenolaTi (phenolaTi-F) at pH 2, unlike results with the unformulated form of the complex. Furthermore, administration of phenolaTi-F in animal drinking water revealed a notable inhibition of tumor growth in Balb/c and immune-deficient (Nude) mice inoculated with CT-26 and HT-29 cells, respectively. In-vivo efficacy was at least similar to that of the corresponding intraperitoneal treatment with phenolaTi-F and the clinically employed oral drug, capecitabine. No body weight loss or clinical signs of toxicity were evident in the phenolaTi-F-treated animals. These findings demonstrate a new convenient mode of cancer treatment through oral administration by safe titanium-based drugs.

Original language	American English
Pages (from-to)	108-112
Number of pages	5
Journal	ChemMedChem
Volume	16
Issue number	1
DOIs	https://doi.org/10.1002/cmdc.202000384
State	Published - 8 Jan 2021

Bibliographical note

Funding Information:
Funding was received from the European Research Council (ERC) under the European Union's Horizon 2020 research (grant agreement no. 779689 to E.Y.T.)

Publisher Copyright:
© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

antitumor agents
metallodrug
nanoformulations
oral administration
titanium

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/cmdc.202000384

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title = "Effective Oral Administration of an Antitumorigenic Nanoformulated Titanium Complex",

abstract = "Abstract: Orally administered anticancer drugs facilitate treatment, but the acidic conditions in the stomach often challenge their availability. PhenolaTi is a TiIV-based nontoxic anticancer drug with marked in-vivo efficacy. We report that nanoformulation protects phenolaTi from decomposition in stomach-like conditions. This is evidenced by similar NMR characteristics and similar in-vitro cytotoxicity toward murine (CT-26) and human (HT-29) colon cancer cells before and after incubation of nanoformulated phenolaTi (phenolaTi-F) at pH 2, unlike results with the unformulated form of the complex. Furthermore, administration of phenolaTi-F in animal drinking water revealed a notable inhibition of tumor growth in Balb/c and immune-deficient (Nude) mice inoculated with CT-26 and HT-29 cells, respectively. In-vivo efficacy was at least similar to that of the corresponding intraperitoneal treatment with phenolaTi-F and the clinically employed oral drug, capecitabine. No body weight loss or clinical signs of toxicity were evident in the phenolaTi-F-treated animals. These findings demonstrate a new convenient mode of cancer treatment through oral administration by safe titanium-based drugs.",

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author = "Gilad Nahari and Ori Braitbard and Liraz Larush and Jacob Hochman and Tshuva, {Edit Y.}",

note = "Funding Information: Funding was received from the European Research Council (ERC) under the European Union's Horizon 2020 research (grant agreement no. 779689 to E.Y.T.) Publisher Copyright: {\textcopyright} 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim",

year = "2021",

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doi = "10.1002/cmdc.202000384",

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AU - Nahari, Gilad

AU - Braitbard, Ori

AU - Larush, Liraz

AU - Hochman, Jacob

AU - Tshuva, Edit Y.

N1 - Funding Information: Funding was received from the European Research Council (ERC) under the European Union's Horizon 2020 research (grant agreement no. 779689 to E.Y.T.) Publisher Copyright: © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

PY - 2021/1/8

Y1 - 2021/1/8

N2 - Abstract: Orally administered anticancer drugs facilitate treatment, but the acidic conditions in the stomach often challenge their availability. PhenolaTi is a TiIV-based nontoxic anticancer drug with marked in-vivo efficacy. We report that nanoformulation protects phenolaTi from decomposition in stomach-like conditions. This is evidenced by similar NMR characteristics and similar in-vitro cytotoxicity toward murine (CT-26) and human (HT-29) colon cancer cells before and after incubation of nanoformulated phenolaTi (phenolaTi-F) at pH 2, unlike results with the unformulated form of the complex. Furthermore, administration of phenolaTi-F in animal drinking water revealed a notable inhibition of tumor growth in Balb/c and immune-deficient (Nude) mice inoculated with CT-26 and HT-29 cells, respectively. In-vivo efficacy was at least similar to that of the corresponding intraperitoneal treatment with phenolaTi-F and the clinically employed oral drug, capecitabine. No body weight loss or clinical signs of toxicity were evident in the phenolaTi-F-treated animals. These findings demonstrate a new convenient mode of cancer treatment through oral administration by safe titanium-based drugs.

AB - Abstract: Orally administered anticancer drugs facilitate treatment, but the acidic conditions in the stomach often challenge their availability. PhenolaTi is a TiIV-based nontoxic anticancer drug with marked in-vivo efficacy. We report that nanoformulation protects phenolaTi from decomposition in stomach-like conditions. This is evidenced by similar NMR characteristics and similar in-vitro cytotoxicity toward murine (CT-26) and human (HT-29) colon cancer cells before and after incubation of nanoformulated phenolaTi (phenolaTi-F) at pH 2, unlike results with the unformulated form of the complex. Furthermore, administration of phenolaTi-F in animal drinking water revealed a notable inhibition of tumor growth in Balb/c and immune-deficient (Nude) mice inoculated with CT-26 and HT-29 cells, respectively. In-vivo efficacy was at least similar to that of the corresponding intraperitoneal treatment with phenolaTi-F and the clinically employed oral drug, capecitabine. No body weight loss or clinical signs of toxicity were evident in the phenolaTi-F-treated animals. These findings demonstrate a new convenient mode of cancer treatment through oral administration by safe titanium-based drugs.

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Effective Oral Administration of an Antitumorigenic Nanoformulated Titanium Complex

Abstract

Bibliographical note

Keywords

UN SDGs

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