Introduction: The overexpression of Human Epidermal Growth Factor Receptor 2 (HER2) is usually associated with aggressive and infiltrating breast cancer (BC) phenotype, and metastases. Functionalized silica-based nanocarriers (SiNPs) can be labeled for in vivo imaging applications and loaded with chemotherapy drugs, making possible the simultaneous noninvasive diagnosis and treatment (theranostic) for HER2-positive BC. Methods: Firstly, FITC-filled SiNPs, were engineered with two different amounts of Hc-TZ (trastuzumab half-chain) per single nanoparticle (1:2 and 1:8, SiNPs to Hc-TZ ratio), which was 99mTc-radiolabeled at histidine residues for ex vivo and in vivo biodistribution evaluations. Secondly, nanoparticles were loaded with DOX and their in vitro and ex vivo/in vivo delivery was assessed, in comparison with liposomal Doxorubicin (Caelyx). Finally, the treatment efficacy of DOX-SiNPs-TZ (1:8 Hc-TZ) was evaluated in vivo by PET and supported by MS-based proteomics profiling of tumors. Results: SiNPs-TZ (1:8 Hc-TZ) tumor uptake was significantly greater than that of SiNPs-TZ (1:2 Hc-TZ) at 6 hours post-injection (p.i.) in ex vivo biodistribution experiment. At 24 h p.i., radioactivity values remained steady. Fluorescence microscopy, confirmed the presence of radiolabeled SiNPs-TZ (1:8 Hc-TZ) within tumor even at later times. SiNPs-TZ (1:8 Hc-TZ) nanoparticles loaded with Doxorubicin (DOX-SiNPs-TZ) showed a similar DOX delivery capability than Caelyx (at 6 h p.i.), in in vitro and ex vivo assays. Nevertheless, at the end of treatment, tumor volume was significantly reduced by DOX-SiNPs-TZ (1:8 Hc-TZ), compared to Caelyx and DOX-SiNPs treatment. Proteomics study identified 88 high stringent differentially expressed proteins comparing the three treatment groups with controls. Conclusion: These findings demonstrated a promising detection specificity and treatment efficacy for our system (SiNPs-TZ, 1:8 Hc-TZ), encouraging its potential use as a new theranostic agent for HER2-positive BC lesions. In addition, proteomic profile confirmed that a set of proteins, related to tumor aggressiveness, were positively affected by targeted nanoparticles.
Rainone, P., De Palma, A., Sudati, F., Roffia, V., Rigamonti, V., Salvioni, L., et al. (2021). 99mTc-radiolabeled silica nanocarriers for targeted detection and treatment of HER2-positive breast cancer. INTERNATIONAL JOURNAL OF NANOMEDICINE, 16, 1943-1960.
|Citazione:||Rainone, P., De Palma, A., Sudati, F., Roffia, V., Rigamonti, V., Salvioni, L., et al. (2021). 99mTc-radiolabeled silica nanocarriers for targeted detection and treatment of HER2-positive breast cancer. INTERNATIONAL JOURNAL OF NANOMEDICINE, 16, 1943-1960.|
|Tipo:||Articolo in rivista - Articolo scientifico|
|Carattere della pubblicazione:||Scientifica|
|Presenza di un coautore afferente ad Istituzioni straniere:||No|
|Titolo:||99mTc-radiolabeled silica nanocarriers for targeted detection and treatment of HER2-positive breast cancer|
|Autori:||Rainone, P; De Palma, A; Sudati, F; Roffia, V; Rigamonti, V; Salvioni, L; Colombo, M; Ripamonti, M; Spinelli, A; Mazza, D; Mauri, P; Moresco, R; Prosperi, D; Belloli, S|
|Data di pubblicazione:||2021|
|Rivista:||INTERNATIONAL JOURNAL OF NANOMEDICINE|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.2147/IJN.S276033|
|Appare nelle tipologie:||01 - Articolo su rivista|