99mTc-Radiolabeled Silica Nanocarriers for Targeted Detection and Treatment of HER2-Positive Breast Cancer.
Int J Nanomedicine
; 16: 1943-1960, 2021.
Article
en En
| MEDLINE
| ID: mdl-33727808
ABSTRACT
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 (12 and 18, 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 (18 Hc-TZ) was evaluated in vivo by PET and supported by MS-based proteomics profiling of tumors.RESULTS:
SiNPs-TZ (18 Hc-TZ) tumor uptake was significantly greater than that of SiNPs-TZ (12 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 (18 Hc-TZ) within tumor even at later times. SiNPs-TZ (18 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 (18 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, 18 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.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
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Portadores de Fármacos
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Tecnecio
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Dióxido de Silicio
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Receptor ErbB-2
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Radiofármacos
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Nanopartículas
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Int J Nanomedicine
Año:
2021
Tipo del documento:
Article
País de afiliación:
Italia