Improving anti-cancer drug delivery performance of magnetic mesoporous silica nanocarriers for more efficient colorectal cancer therapy
| Autor: | Maryam Moghaddam Matin, Ahmad Reza Bahrami, Sonia Iranpour, Amir SHokooh Saljooghi, Sirous Nekooei |
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| Rok vydání: | 2021 |
| Předmět: |
Biodistribution
Aptamer medicine.medical_treatment Drug delivery system Biomedical Engineering Pharmaceutical Science Medicine (miscellaneous) Antineoplastic Agents Bioengineering CHO Cells pH-sensitive gatekeeper Applied Microbiology and Biotechnology Targeted therapy Mice Cricetulus Cricetinae Medical technology medicine Animals Humans Doxorubicin R855-855.5 Magnetic mesoporous silica NPs Drug Carriers Tumor microenvironment Chemistry Research Silicon Dioxide Colorectal cancer Mice Inbred C57BL Theranostic Targeted drug delivery Drug delivery Cancer research Nanoparticles Molecular Medicine Nanocarriers Colorectal Neoplasms HT29 Cells TP248.13-248.65 Biotechnology medicine.drug |
| Zdroj: | Journal of Nanobiotechnology Journal of Nanobiotechnology, Vol 19, Iss 1, Pp 1-22 (2021) |
| ISSN: | 1477-3155 |
| DOI: | 10.1186/s12951-021-01056-3 |
| Popis: | Background Improving anti-cancer drug delivery performance can be achieved through designing smart and targeted drug delivery systems (DDSs). For this aim, it is important to evaluate overexpressed biomarkers in the tumor microenvironment (TME) for optimizing DDSs. Materials and methods Herein, we designed a novel DDS based on magnetic mesoporous silica core–shell nanoparticles (SPION@MSNs) in which release of doxorubicin (DOX) at the physiologic pH was blocked with gold gatekeepers. In this platform, we conjugated heterofunctional polyethylene glycol (PEG) onto the outer surface of nanocarriers to increase their biocompatibility. At the final stage, an epithelial cell adhesion molecule (EpCAM) aptamer as an active targeting moiety was covalently attached (Apt-PEG-Au@NPs-DOX) for selective drug delivery to colorectal cancer (CRC) cells. The physicochemical properties of non-targeted and targeted nanocarriers were fully characterized. The anti-cancer activity, cellular internalization, and then the cell death mechanism of prepared nanocarriers were determined and compared in vitro. Finally, tumor inhibitory effects, biodistribution and possible side effects of the nanocarriers were evaluated in immunocompromised C57BL/6 mice bearing human HT-29 tumors. Results Nanocarriers were successfully synthesized with a mean final size diameter of 58.22 ± 8.54 nm. Higher cytotoxicity and cellular uptake of targeted nanocarriers were shown in the EpCAM-positive HT-29 cells as compared to the EpCAM-negative CHO cells, indicating the efficacy of aptamer as a targeting agent. In vivo results in a humanized mouse model showed that targeted nanocarriers could effectively increase DOX accumulation in the tumor site, inhibit tumor growth, and reduce the adverse side effects. Conclusion These results suggest that corporation of a magnetic core, gold gatekeeper, PEG and aptamer can strongly improve drug delivery performance and provide a theranostic DDS for efficient CRC therapy. Graphic abstract |
| Databáze: | OpenAIRE |
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