Following cytotoxic nanoconjugates from injection to halting the cell cycle machinery and its therapeutic implications in oral cancer
| Autor: | Sahar M. El-Sheikh, Ghada M. Mourad, Zeinab E. Darwish, Hend Mohamed Abdel Hamid, Hanaa M. Donia, Marwa M. Afifi |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Cancer Research FGFR1 inhibitor Oral cancer Population Metal Nanoparticles 02 engineering and technology lcsh:RC254-282 03 medical and health sciences Drug Delivery Systems 0302 clinical medicine In vivo Antineoplastic Combined Chemotherapy Protocols Genetics medicine Gold nanoparticles Animals education education.field_of_study Mesocricetus Chemistry Cell Cycle Cell cycle lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens 021001 nanoscience & nanotechnology Oncology 030220 oncology & carcinogenesis Drug delivery Cancer cell 5-flourouracil Cancer research Camptothecin Mouth Neoplasms Fluorouracil Gold Nanocarriers 0210 nano-technology Nanoconjugates Research Article medicine.drug |
| Zdroj: | BMC Cancer BMC Cancer, Vol 21, Iss 1, Pp 1-16 (2021) |
| ISSN: | 1471-2407 |
| DOI: | 10.1186/s12885-021-07849-x |
| Popis: | Background The concept of personalized therapy has been proven to be a promising approach. A popular technique is to utilize gold nanoparticles (AuNPs) as drug delivery vectors for cytotoxic drugs and small molecule inhibitors to target and eradicate oral cancer cells in vitro and in vivo. Both drug and nanocarrier designs play important roles in the treatment efficacy. In our study, we standardized the nanosystem regarding NPs type, size, surface ligands and coverage percentage leaving only the drugs mode of action as the confounding variable. We propose that similarly constructed nanoparticles (NPs) can selectively leverage different conjugated drugs irrelevant to their original mode of action. If proven, AuNPs may have a secondary role beyond bypassing cancer cell membrane and delivering their loaded drugs. Methods We conjugated 5- fluorouracil (5Fu), camptothecin (CPT), and a fibroblast growth factor receptor1-inhibitor (FGFR1i) to gold nanospheres (AuNSs). We followed their trajectories in Syrian hamsters with chemically induced buccal carcinomas. Results Flow cytometry and cell cycle data shows that 5Fu- and CPT- induced a similar ratio of S-phase cell cycle arrest as nanoconjugates and in their free forms. On the other hand, FGFR1i-AuNSs induced significant sub-G1 cell population compared with its free form. Despite cell cycle dynamics variability, there was no significant difference in tumor cells’ proliferation rate between CPT-, 5Fu- and FGFR1i- AuNSs treated groups. In our in vivo model, FGFR1i-AuNSs induced the highest tumor reduction rates followed by 5Fu- AuNSs. CPT-AuNSs induced significantly lower tumor reduction rates compared with the 5Fu- and FGFR1i- AuNSs despite showing similar proliferative rates in tumor cells. Conclusions Our data indicates that the cellular biological events do not predict the outcome seen in our in vivo model. Furthermore, our results suggest that AuNSs selectively enhance the therapeutic effect of small molecule inhibitors such as FGFR1i than potent anticancer drugs. Future studies are required to better understand the underlying mechanism. |
| Databáze: | OpenAIRE |
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