Naslov
Imaging mass spectrometry differentiates the effects of doxorubicin formulations on non-targeted tissues
(Imaging mass spectrometry differentiates the effects of doxorubicin formulations on non-targeted tissues)

Autori
Debeljak, Željko ; Vinković Vrček, Ivana ; Drinković, Nikša ; Micek, Vedran, Galić, Emerik, Gorup, Dunja ; Ćurlin, Marija ; Mandić, Dario ; Bandjak, Ana ; Pem, Barbara ; Kalčec, Nikolina ; Ilić, Krunoslav ; Pavičić, Ivan ; Mimica, Suzana ; Günday-Türeli ; Nazende ; Türeli, Emre

Izvornik
Analyst (0003-2654) 147 (2022); 3201-3208

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
mass spectrometry ; imaging ; doxorubicin ; nanoformulation

Sažetak
Administration of cytotoxic agents like doxorubicin (DOX) is restrained by the effects on different non-targeted/non-cancerous tissues, which instigates the development of nano-enabled drug delivery systems, among others. In this study, imaging mass spectrometry (IMS) was selected to examine the effects of DOX nanoformulations on non-targeted tissues. Chemical alterations induced by liposomal (LPS) and poly (lactic-co-glycolic acid) (PLG) nanoformulations were assessed against the ones induced by the conventional (CNV) formulation. Kidney cryosections of the treated and control Wistar rats were used as a model of the non-targeted tissue and analyzed by MALDI TOF IMS in the 200- 1000 Da m/z range. Principal component analysis (PCA) and Volcano plots of the average mass spectra demonstrated a large overlap between treatments. However, the Venn diagram of significant m/z values revealed a nanoformulation- specific fingerprint consisting of 59 m/z values, which set them apart from the CNV formulation characterized by the fingerprint of 22 significant m/z values. Fingerprint m/z values that were putatively annotated by metabolome database search were linked to apoptosis, cell migration and proliferation. In CNV and PLG cases, false discovery rate adjusted ANOVA showed no differences in the spatial distribution of fingerprint m/z values between the histological substructures like glomeruli and convoluted tubules indicating their tissue-nonselective effect. LPS caused the least significant changes in m/z values and some of the LPS-specific fingerprint m/z values were primarily distributed in the glomeruli. The IMS based procedure successfully differentiated the effects of DOX formulations on the model non-targeted tissue, thus indicating the importance of IMS in effective drug development.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Temeljne medicinske znanosti, Farmacija

POVEZANOST RADA