Self-assembled poly(ε-caprolactone)-g-chondroitin sulfate copolymers as an intracellular doxorubicin delivery carrier against lung cancer cells

Abstract

The aim of this study was to utilize self-assembled polycaprolactone (PCL)-grafted chondroitin sulfate (CS) as an anticancer drug carrier. We separately introduced double bonds to the hydrophobic PCL and the hydrophilic CS. The modified PCL was reacted with the modified CS through a radical reaction (CSMA-g-PCL). The copolymer without doxorubicin (DOX) was noncytotoxic in CRL-5802 and NCI-H358 cells at a concentration ranging from 5–1000 μg/mL and DOX-loaded CSMA-g-PCL (Micelle DOX) had the lowest inhibitory concentration of 50% cell growth values against the NCI-H358 cells among test samples. The cellular uptake of Micelle DOX into the cells was confirmed by flow cytometric data and confocal laser scanning microscopic images. The in vivo tumor-targeting efficacy of Micelle DOX was realized using an NCI-H358 xenograft nude mouse model. The mice administered with Micelle DOX showed suppressed growth of the NCI-H358 lung tumor compared with those administered with phosphate-buffered saline and free DOX.

Keywords:

• chondroitin sulfate
• poly(ε-caprolactone)
• amphiphilic copolymers
• micelles
• cellular uptake

Acknowledgments/Disclosure

We are grateful for the financial support of the National Science Council of Taiwan under grant numbers NSC 98-2320-B-037-002 and NSC 101-2325-B-037-006 and the support of the Kaohsiung Medical University Research Foundation. The authors report no conflicts of interest in this work.

Supplementary figures

Figure S1 (A) ¹H-NMR and (B) MALDI-MS of MeO-PCL-OH; (C) ¹H-NMR of MeO-PCL-AC.

Abbreviations: NMR, Nuclear magnetic resonance; MALDI-MS, matrix-assisted laser desorption/ionization-mass spectrometry; MeO-PCL-OH, Methoxy-capped poly(ε-caprolactone); MeO-PCL-Ac, Methoxy-capped poly(ε-caprolactone) acrylate.

Figure S2 Critical micelle concentration measurement of CSMA-g-PCL using pyrene as a probe.

Figure S3 (A) DLS histograms and (B) zeta potentials of CSMA-g-PCL with DOX (Micelle DOX) or without DOX (Micelle).

Abbreviations: DSL, Dynamic light scattering; CSMA-g-PCL, Poly(ε-caprolactone)-g-methacrylated chondroitin sulfate; DOX, Doxorubicin.

Figure S4 Cell viability of (A) CRL-5802 and (B) NCI-H358 cells exposed to free DOX, DOX-loaded liposome (Lipo DOX), and DOX-loaded CSMA-g-PCL (Micelle DOX) for 24 hours (n = 8).

Abbreviations: DOX, Doxorubicin; Lipo DOX, Doxorubicin-encapsulated liposome; CSMA-g-PCL, Poly(ε-caprolactone)-g-methacrylated chondroitin sulfate.