RESUMO
A theranostic nanosystem based on indocyanine green (ICG) covalently conjugated to mesoporous silica nanoparticles (MSNs) loaded with the anticancer drug mitoxantrone (MTX) is proposed as an innovative photoacoustic probe. Taking advantage of the characteristic PA signal displayed by both ICG and MTX, a PA-ratiometric approach was applied to assess the drug release profile from the MSNs. After complete in vitro characterization of the nanoprobe, a proof-of-concept study has been carried out in tumour-bearing mice to evaluate in vivo its effectiveness for cancer imaging and chemotherapeutic agent delivery.
Assuntos
Antineoplásicos , Meios de Contraste , Mitoxantrona , Nanopartículas , Neoplasias Experimentais , Técnicas Fotoacústicas , Fototerapia , Dióxido de Silício , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Meios de Contraste/química , Meios de Contraste/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Humanos , Verde de Indocianina/química , Verde de Indocianina/farmacologia , Camundongos , Mitoxantrona/química , Mitoxantrona/farmacologia , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Nanomedicina TeranósticaRESUMO
The water exchange lifetime (τ(i)) through red blood cell (RBC) membranes can be measured by analyzing the water protons bi-exponential T1 and T2 curves when RBCs are suspended in a medium supplemented with paramagnetic species. Since the seminal papers published in the early '70s of the previous century, paramagnetic Mn(2+) ions were used for doping the extracellular compartment in the RBCs suspension. The obtained τ(i) values fall in the range of 9.8-14 ms. Conversely, other physic-chemical measurements afforded longer τ(i) values. Herein, it is shown that the replacement of Mn(2+) with the highly stable, hydrophilic Gd(III) complexes used as paramagnetic magnetic resonance imaging (MRI) contrast agents led to measure τ(iI) values of 19.1 ± 0.65 ms at 25 ° C. The observed difference is ascribed to the occurrence of enhanced permeability of RBC membrane in the presence of Mn(2+) ions. This view finds support from the observation that an analogous behavior was shown in the presence of other divalent cations, such Ca(2+) and Zn(2+) ions. A possible role of scramblase has been hypothesized. Finally, τ(i) has been measured in presence of alcohols to show that the herein proposed method can detect minor changes in RBC membranes' stiffness upon the incorporation of aliphatic alcohols.