Mesoporous Silica Nanoparticles Enhance the Anticancer Efficacy of Platinum(IV)-Phenolate Conjugates in Breast Cancer Cell Lines
2022
Аутори:
Predarska, IvanaSaoud, Mohamad
Drača, Dijana
Morgan, Ibrahim
Komazec, Teodora
Eichhorn, Thomas
Mihajlović, Ekatarina
Dunđerović, Duško
Mijatović, Sanja
Maksimović-Ivanić, Danijela
Hey-Hawkins, Evamarie
Kaluđerović, Goran N.
Тип документа:
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт:
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.
Кључне речи:
platinum(IV) conjugates; cisplatin; phenolic acid; nanoparticles; drug delivery; breast cancerИзвор:
Nanomaterials, 2022, 12, 21, 3767-Финансирање / пројекти:
- FEM POWER ESF Saxony-Anhalt WISSENSCHAFT Chancengleichheit
- Graduate School “Building with Molecules and Nanoobjects (BuildMoNa)”, the Research Academy Leipzig
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200007 (Универзитет у Београду, Институт за биолошка истраживања 'Синиша Станковић') (RS-MESTD-inst-2020-200007)
DOI: 10.3390/nano12213767
ISSN: 2079-4991
PubMed: 36364539