Folate-Appended β-Cyclodextrin as a Promising Tumor Targeting Carrier for Antitumor Drugs in Vitro and in Vivo
| Autor: | Takahiro Koshigoe, Ayaka Okamatsu, Hidetoshi Arima, Taishi Higashi, Kenjiro Hattori, Risako Onodera, Keiichi Motoyama, Yasutaka Shimada, Tomoko Takeuchi |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Cell Survival Biomedical Engineering Pharmaceutical Science Antineoplastic Agents Bioengineering Pharmacology KB Cells Mice Structure-Activity Relationship chemistry.chemical_compound Drug Delivery Systems Folic Acid In vivo Tumor Cells Cultured medicine Animals Humans Doxorubicin Caproates A549 cell Drug Carriers Mice Inbred BALB C Dose-Response Relationship Drug Molecular Structure Chemistry beta-Cyclodextrins Organic Chemistry Neoplasms Experimental In vitro Paclitaxel Folate receptor Drug delivery Drug Screening Assays Antitumor Drug carrier Biotechnology medicine.drug |
| Zdroj: | Bioconjugate Chemistry. 24:724-733 |
| ISSN: | 1520-4812 1043-1802 |
| Popis: | A large number of antitumor drug delivery carriers based on passive targeting and/or active targeting have been developed. However, encapsulation of antitumor drugs into these drug carriers is often complicated, and antitumor activities of these targeting systems are not satisfactory. In the present study, we first prepared heptakis-6-folic acid (FA)-appended β-cyclodextrin (β-CyD) possessing two caproic acids between FA and a β-CyD molecule as a spacer (Fol-c(2)-β-CyD) and evaluated the potential as a novel tumor targeting carrier for antitumor drugs through a complexation. Fol-c(2)-β-CyD formed an inclusion complex with doxorubicin (DOX) at a 1:1 molar ratio with a markedly high stability constant (10(6) M(-1)). Cellular uptake of DOX was increased by the addition of Fol-c(2)-β-CyD in KB cells, a folate receptor-α (FR-α)-positive cell line. Additionally, Fol-c(2)-β-CyD increased in vitro antitumor activities of antitumor drugs such as DOX, vinblastine (VBL), and paclitaxel (PTX) in KB cells, but not in A549 cells, a FR-α-negative cell line. The complex of DOX with Fol-c(2)-β-CyD markedly increased antitumor activity of DOX, not only after intratumoral administration but also after intravenous administration to mice subcutaneously inoculated Colon-26 cells, a FR-α-positive cell line. These findings suggest that Fol-c(2)-β-CyD could be useful as a promising antitumor drug carrier. |
| Databáze: | OpenAIRE |
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