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99mTc-Radiolabeled Silica Nanocarriers for Targeted Detection and Treatment of HER2-Positive Breast Cancer
| Content Provider | Scilit |
|---|---|
| Author | Rainone, Paolo Palma, Antonella De Sudati, Francesco Roffia, Valentina Rigamonti, Valentina Salvioni, Lucia Colombo, Miriam Ripamonti, Marilena Spinelli, Antonello Enrico Mazza, Davide Mauri, Pierluigi Moresco, Rosa Maria Prosperi, Davide Belloli, Sara |
| Copyright Year | 2021 |
| Description | Journal: International Journal of Nanomedicine |
| 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 (1:2 and 1:8, SiNPs to Hc-TZ ratio), which was$ ^{99m}$Tc-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. |
| Related Links | https://www.dovepress.com/getfile.php?fileID=67411 |
| Ending Page | 1960 |
| Page Count | 18 |
| Starting Page | 1943 |
| e-ISSN | 11782013 |
| DOI | 10.2147/ijn.s276033 |
| Journal | International Journal of Nanomedicine |
| Volume Number | ume 16 |
| Language | English |
| Publisher | Informa UK Limited |
| Publisher Date | 2021-03-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: International Journal of Nanomedicine Her2-positive Bc Targeted Silica Nanoparticles Tz-half Chain Conjugation 99mtc-radiolabeling Spect Imaging Doxorubicin-loaded Nanoparticles |
| Content Type | Text |
