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Predarska, Ivana [Author]; Saoud, Mohamad [Author]; Draca, Dijana [Author]; Morgan, Ibrahim [Author]; Komazec, Teodora [Author]; Eichhorn, Thomas [Author]; Mihajlovi, Ekatarina [Author]; Dunderovic, Duško [Author]; Mijatovic, Sanja [Author]; Maksimovic-Ivanic´, Danijela [Author]; Hey-Hawkins, Evamarie [Author]; Kaluderovic, Goran N. [Author]

Mesoporous Silica Nanoparticles Enhance the Anticancer Efficacy of Platinum(IV)-Phenolate Conjugates in Breast Cancer Cell Lines

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  • Media type: E-Article
  • Title: Mesoporous Silica Nanoparticles Enhance the Anticancer Efficacy of Platinum(IV)-Phenolate Conjugates in Breast Cancer Cell Lines
  • Contributor: Predarska, Ivana [Author]; Saoud, Mohamad [Author]; Draca, Dijana [Author]; Morgan, Ibrahim [Author]; Komazec, Teodora [Author]; Eichhorn, Thomas [Author]; Mihajlovi, Ekatarina [Author]; Dunderovic, Duško [Author]; Mijatovic, Sanja [Author]; Maksimovic-Ivanic´, Danijela [Author]; Hey-Hawkins, Evamarie [Author]; Kaluderovic, Goran N. [Author]
  • Published: Basel : MDPI, [2024]
  • Published in: Nanomaterials ; 12,21 (2022), Seite 1-23
  • Language: German
  • DOI: 10.3390/nano12213767
  • Keywords: drug delivery ; nanoparticles ; platinum(IV) conjugates ; cisplatin ; phenolic acid ; breast cancer
  • Origination:
  • Footnote:
  • Description: The main reasons for the limited clinical efficacy of the platinum(II)-based agent cisplatininclude drug resistance and significant side effects. Due to their better stability, as well as thepossibility to introduce biologically active ligands in their axial positions constructing multifunctionalprodrugs, creating platinum(IV) complexes is a tempting strategy for addressing these limitations.Another strategy for developing chemotherapeutics with lower toxicity relies on the ability ofnanoparticles to accumulate in greater quantities in tumor tissues through passive targeting. Tocombine the two approaches, three platinum(IV) conjugates based on a cisplatin scaffold containingin 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 differenthuman breast cancer cell lines, while upon immobilization, superior antiproliferative activity withmarkedly increased cytotoxicity (more than 1000-fold lower IC50 values) compared to cisplatin wasobserved. 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 thesecompounds 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 themitotic rate.
  • Access State: Open Access
  • Rights information: Attribution (CC BY)