Mesoporous Silica Nanoparticles Enhance the Anticancer Efficacy of Platinum(IV)-Phenolate Conjugates in Breast Cancer Cell Lines
![](/themes/MirageIBISS//images/openAccess.png)
2022
Authors:
Predarska, IvanaSaoud, Mohamad
Drača, Dijana
![](/themes/MirageIBISS/images/orcid.png)
Morgan, Ibrahim
Komazec, Teodora
![](/themes/MirageIBISS/images/orcid.png)
Eichhorn, Thomas
Mihajlović, Ekatarina
![](/themes/MirageIBISS/images/orcid.png)
Dunđerović, Duško
Mijatović, Sanja
![](/themes/MirageIBISS/images/orcid.png)
Maksimović-Ivanić, Danijela
![](/themes/MirageIBISS/images/orcid.png)
Hey-Hawkins, Evamarie
Kaluđerović, Goran N.
Document Type:
Article (Published version)
Metadata
Show full item recordAbstract:
The main reasons for the limited clinical efficacy of the platinum(II)-based agent cisplatin
include drug resistance and significant side effects. Due to their better stability, as well as the
possibility to introduce biologically active ligands in their axial positions constructing multifunctional
prodrugs, creating platinum(IV) complexes is a tempting strategy for addressing these limitations.
Another strategy for developing chemotherapeutics with lower toxicity relies on the ability of
nanoparticles to accumulate in greater quantities in tumor tissues through passive targeting. To
combine the two approaches, three platinum(IV) conjugates based on a cisplatin scaffold containing
in the axial positions derivatives of caffeic and ferulic acid were prepared and loaded into SBA-
15 to produce the corresponding mesoporous silica nanoparticles (MSNs). The free platinum(IV)
conjugates demonstrated higher or comparable activity with respect to cisplatin against different
human breast cancer cell lines, while upon immobilization, superior antiproliferative activity with
markedly increased cytotoxicity (more than 1000-fold lower IC50 values) compared to cisplatin was
observed. Mechanistic investigations with the most potent conjugate, cisplatin-diacetyl caffeate (1),
and the corresponding MSNs (SBA-15|1) in a 4T1 mouse breast cancer cell line showed that these
compounds induce apoptotic cell death causing strong caspase activation. In vivo, in BALB/c mice,
1 and SBA-15|1 inhibited the tumor growth while decreasing the necrotic area and lowering the
mitotic rate.
Keywords:
platinum(IV) conjugates; cisplatin; phenolic acid; nanoparticles; drug delivery; breast cancerSource:
Nanomaterials, 2022, 12, 21, 3767-Funding / projects:
- FEM POWER ESF Saxony-Anhalt WISSENSCHAFT Chancengleichheit
- Graduate School “Building with Molecules and Nanoobjects (BuildMoNa)”, the Research Academy Leipzig
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
DOI: 10.3390/nano12213767
ISSN: 2079-4991
PubMed: 36364539