Synergistic antitumor activity of a self-assembling camptothecin and capecitabine hybrid prodrug for improved efficacy
| Autor: | Honggang Cui, Andrew G. Cheetham, QuanCheng Kan, Wang Ma, Weifang Zhang, Hao Su, Yuzhu Wang |
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| Rok vydání: | 2017 |
| Předmět: |
Drug
Antimetabolites Antineoplastic Cell Survival media_common.quotation_subject Pharmaceutical Science macromolecular substances 02 engineering and technology Pharmacology Conjugated system 010402 general chemistry 01 natural sciences Capecitabine Microscopy Electron Transmission Cell Line Tumor Antineoplastic Combined Chemotherapy Protocols medicine Humans Prodrugs Cytotoxicity media_common Chemistry Combination chemotherapy Prodrug 021001 nanoscience & nanotechnology Antineoplastic Agents Phytogenic Nanostructures 0104 chemical sciences Drug Liberation Drug delivery Camptothecin 0210 nano-technology medicine.drug |
| Zdroj: | Journal of Controlled Release. 263:102-111 |
| ISSN: | 0168-3659 |
| DOI: | 10.1016/j.jconrel.2017.01.015 |
| Popis: | The direct use of anticancer drugs to create their own nanostructures is an emerging concept in the field of drug delivery to obtain nanomedicines of high drug loading and high reproducibility, and the combination use of two or more drugs has been a proven clinical strategy to enhance therapeutic outcomes. We report here the synthesis, assembly and cytotoxicity evaluation of self-assembling hybrid prodrugs containing both camptothecin (CPT) and a capecitabine (Cap) analogue. CPT and Cap molecules were conjugated onto a short β-sheet-forming peptide (Sup35) to yield three different self-assembling prodrugs (dCPT-Sup35, CPT-Cap-Sup35 and dCap-Sup35). We found that the chemical structure of conjugated drugs could strongly influence their assembled morphology as well as their structural stability in aqueous solution. With a decrease in number of CPT units, the resulting nanostructures exhibited a morphological transformation from nanofibers (dCPT-Sup35) to filaments (CPT-Cap-Sup35) then to spherical particles (dCap-Sup35). Notably, the hybrid CPT-Cap prodrug showed a synergistic effect and significantly enhanced potency against three esophageal adenocarcinoma cell lines compared with the two homo-prodrugs (dCPT-Sup35 and dCap-Sup35) as well as free parent drugs (CPT, 5-Fu and CPT/5-FU mixture (1:1)). We believe this work represents a conceptual advancement in integrating two structurally distinct drugs of different action mechanisms into a single self-assembling hybrid prodrug to construct self-deliverable nanomedicines for more effective combination chemotherapy. |
| Databáze: | OpenAIRE |
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