Carbosilane ruthenium metallodendrimer as alternative anti-cancer drug carrier in triple negative breast cancer mouse model: A preliminary study

[Display omitted] •Ruthenium metallodendrimer CRD13 forms stable nanocomplexes with DOX, 5-Fu, and MTX.•CRD13/DOX system was effective against human breast cancer MDA-MB-231 cells in vitro.•CRD13/DOX complex provide to decrease the tumor mass in mice models with TNBC. The carbosilane metallodendrime...

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Published in:International journal of pharmaceutics 2023-04, Vol.636, p.122784-122784, Article 122784
Main Authors: Michlewska, Sylwia, Maly, Marek, Wójkowska, Dagmara, Karolczak, Kamil, Skiba, Elżbieta, Hołota, Marcin, Kubczak, Małgorzata, Ortega, Paula, Watala, Cezary, Javier de la Mata, F., Bryszewska, Maria, Ionov, Maksim
Format: Article
Language:English
Subjects:
Animals
Anticancer drug
Antineoplastic Agents - chemistry
Cell Line, Tumor
Computer Simulation
Coordination Complexes - chemistry
Cytotoxicity
Dendrimer
Drug Carriers
Drug delivery
Drug Screening Assays, Antitumor
Humans
In vitro
In vivo
Mice
Molecular dynamics
Molecular simulations
Molecular Structure
Ruthenium
Ruthenium - chemistry
Triple Negative Breast Neoplasms - drug therapy
Tumor weight
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Summary:[Display omitted] •Ruthenium metallodendrimer CRD13 forms stable nanocomplexes with DOX, 5-Fu, and MTX.•CRD13/DOX system was effective against human breast cancer MDA-MB-231 cells in vitro.•CRD13/DOX complex provide to decrease the tumor mass in mice models with TNBC. The carbosilane metallodendrimer G1-[[NCPh(o-N)Ru(η6- p-cymene)Cl]Cl]4 (CRD13), based on an arene Ru(II) complex coordinated to imino-pyridine surface groups, has been conjugated with anti-cancer drugs. Ruthenium in the positively-charged dendrimer structure allows this nanoparticle to be considered as an anticancer drug carrier, made more efficient because ruthenium has anticancer properties. The ability of CRD13 to form complexes with Doxorubicin (DOX), 5-Fluorouracil (5-Fu), and Methotrexate (MTX) has been evaluated using zeta potential measurement, transmission electron microscopy (TEM) and computer simulation. The results show that it forms stable nanocomplexes with all those drugs, enhancing their effectiveness against MDA-MB-231 cancer cells. In vivo tests indicate that the CRD13/DOX system caused a decrease of tumor weight in mice with triple negative breast cancer. However, the tumors were most visibly reduced when naked dendrimers were injected.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2023.122784