Journal
CHEMMEDCHEM
Volume 16, Issue 1, Pages 108-112Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cmdc.202000384
Keywords
antitumor agents; metallodrug; nanoformulations; oral administration; titanium
Categories
Funding
- European Research Council (ERC) under the European Union [779689]
- European Research Council (ERC) [779689] Funding Source: European Research Council (ERC)
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Orally administered nanoformulated PhenolaTi can protect the drug from decomposition in acidic conditions, showing similar in-vitro cytotoxicity towards colon cancer cells and inhibiting tumor growth in mice when administered in their drinking water. This provides a new convenient and effective mode of cancer treatment through safe titanium-based drugs.
: 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 markedin-vivoefficacy. We report that nanoformulation protects phenolaTi from decomposition in stomach-like conditions. This is evidenced by similar NMR characteristics and similarin-vitrocytotoxicity 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-vivoefficacy 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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