Folic Acid Modified Polymeric Micelles for Intravesical Instilled Chemotherapy

• Published in: Chinese journal of polymer science Vol. 36; no. 4; pp. 479 - 487
• Main Authors: Zhou, Dan-Hua, Zhang, Guan, Yu, Qing-Song, Gan, Zhi-Hua
• Format: Journal Article
• Language: English
• Published: Beijing Chinese Chemical Society and Institute of Chemistry, CAS 01.04.2018; Springer Nature B.V
• Subjects: Bladder; Bladder cancer; Block copolymers; Cancer; Characterization and Evaluation of Materials; Chemical synthesis; Chemistry; Chemistry and Materials Science; Chemotherapy; Condensed Matter Physics; Conjugation; Doxorubicin; Drug carriers; Drug delivery systems; Fluorescein; Fluorescence; Folic acid; Industrial Chemistry/Chemical Engineering; Micelles; Polyethylene glycol; Polymer Sciences; Toxicity; Targeted drug delivery; Superficial bladder cancer; Intravesical instilled chemotherapy; Micelles; Folic acid
• ISSN: 0256-7679; 1439-6203
• DOI: 10.1007/s10118-018-2009-y

In this study, a targeting micellar drug delivery system was developed for intravesical instilled chemotherapy of bladder cancer. The amphiphilic diblock copolymer poly( ε -caprolactone)-block-poly(ethylene glycol) (PCL- b -PEO) with functional amino group (NH 2 ) at the end of PEO block was synthesized. Then the copolymer was conjugated with folic acid (FA) and fluorescein isothiocyannate (FITC) via the PEO-NH 2 terminus, and then assembled into micelles with the target moiety and fluorescence labeling. In addition, drug loaded micelles were also fabricated with anticancer drug doxorubicin (DOX) encapsulated in the hydrophobic core. The micelles were characterized in terms of size, drug loaded efficiency and critical micellization concentration (CMC) by means of DLS, UV and fluorescence spectra. In vitro cellular uptake and cytotoxicity studies showed that FA modified PCL- b -PEO-FA micelles have a greater targeting efficiency to human bladder cancer cell (T-24 cell) compared to PCL-b-PEO-NH 2 micelles due to the conjugation of FA on the surface, while no targeting effect to normal tissue originated human embryonic kidney 293 (HEK-293) cells was observed, enabling the micelles a promising drug carrier for intravesical instilled chemotherapy of bladder cancer.