TY - JOUR

T1 - Amphiphilic Triazine‐Phosphorus Metallodendrons Possessing Anti‐Cancer Stem Cell Activity

AU - Apartsin, Evgeny K.

AU - Knauer, Nadezhda

AU - Kahlert, Ulf Dietrich

AU - Caminade, Anne Marie

N1 - Funding Information: Funding: The project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska‐Curie grant agreement No 844217. N.K. ap‐ preciates the financial support from the Heinrich‐Heine University Düsseldorf, Germany within the STIBET programme. This article is based upon work from COST Action CA 17140 “Cancer Nano‐ medicine from the Bench to the Bedside” supported by COST (European Cooperation in Science and Technology). The financial support from the CNRS is also appreciated. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022/2

Y1 - 2022/2

N2 - Dendritic molecules bearing metal complexes in their structure (metallodendrimers and metallodendrons) are considered prospective therapeutic entities. In particular, metallodendrons raise interest as antitumor agents for the treatment of poorly curable or drug‐resistant tumors. Herein, we have synthesized amphiphilic triazine‐phosphorus dendrons bearing multiple copper (II) or gold (III) complexes on the periphery and a branched hydrophobic fragment at the focal point. Due to their amphiphilic nature, metallodendrons formed single micelles (mean diameter ~9 nm) or multi‐micellar aggregates (mean diameter ~60 nm) in a water solution. We have tested the antitumor activity of amphiphilic metallodendrons towards glioblastoma, a malignant brain tumor with a notoriously high level of therapy resistance, as a model disease. The metallodendrons exhibit higher cytotoxic activity towards glioblastoma stem cells (BTSC233, JHH520, NCH644, and SF188 cell lines) and U87 glioblastoma cells (IC50 was 3–6 μM for copper‐containing dendron and 11–15 μM for gold‐containing dendron) in comparison with temozolomide (IC50 >100 μM)—the clinical standard of care for glioblastoma. Our findings show the potential of metallodendron‐based nanoformulations as antitumor entities.

AB - Dendritic molecules bearing metal complexes in their structure (metallodendrimers and metallodendrons) are considered prospective therapeutic entities. In particular, metallodendrons raise interest as antitumor agents for the treatment of poorly curable or drug‐resistant tumors. Herein, we have synthesized amphiphilic triazine‐phosphorus dendrons bearing multiple copper (II) or gold (III) complexes on the periphery and a branched hydrophobic fragment at the focal point. Due to their amphiphilic nature, metallodendrons formed single micelles (mean diameter ~9 nm) or multi‐micellar aggregates (mean diameter ~60 nm) in a water solution. We have tested the antitumor activity of amphiphilic metallodendrons towards glioblastoma, a malignant brain tumor with a notoriously high level of therapy resistance, as a model disease. The metallodendrons exhibit higher cytotoxic activity towards glioblastoma stem cells (BTSC233, JHH520, NCH644, and SF188 cell lines) and U87 glioblastoma cells (IC50 was 3–6 μM for copper‐containing dendron and 11–15 μM for gold‐containing dendron) in comparison with temozolomide (IC50 >100 μM)—the clinical standard of care for glioblastoma. Our findings show the potential of metallodendron‐based nanoformulations as antitumor entities.

KW - Copper

KW - Cytotoxicity

KW - Dendrons

KW - Gold

KW - Metallodrugs

KW - Nanomedicine

KW - Phosphorus

KW - Supramolecular associates

KW - Tumor stem cells

UR - http://www.scopus.com/inward/record.url?scp=85124670053&partnerID=8YFLogxK

U2 - 10.3390/pharmaceutics14020393

DO - 10.3390/pharmaceutics14020393

M3 - Article

C2 - 35214126

AN - SCOPUS:85124670053

VL - 14

JO - Pharmaceutics

JF - Pharmaceutics

SN - 1999-4923

IS - 2

M1 - 393

ER -