Visible light and pH-responsive star copolymer and doxorubicin-polymer conjugate micelles for combination drug delivery and bioimaging

Abstract

Amphiphilic 3-arm star copolymer containing visible light-cleavable BODIPY group and pH-responsive imine bonds at the junction of hydrophilic poly(ethylene glycol) (PEG) and two poly(ε-caprolactone) (PCL) arms was synthesized by the combination of ring-opening polymerization (ROP) and click chemistry. The formation and stimuli-responsive disruption of micelles were analyzed using dynamic light scattering and transmission electron microscopy. Dual stimuli-responsive release of anticancer drugs Doxorubicin (Dox) and Camptothecin (CPT) from the micelles was studied. Micellar assemblies containing Dox conjugated to PEG-BODIPY through imine bonds were prepared and controlled release of Dox in response to visible light and pH was shown. CPT and Dox-loaded star copolymer micelles as well as CPT loaded Dox-conjugated micelles were used in cellular uptake studies on MDA-MB 231 cells, and the synergistic effect of the two stimuli on the release of the two drugs was demonstrated inside the cells. Micellar assemblies also showed excellent bioimaging properties in the cellular uptake studies.

GRAPHICAL ABSTRACT

Keywords:

• Micelles
• BODIPY
• drug conjugate
• visible light-responsive
• pH-responsive

Acknowledgements

NBB thanks CSIR for the Senior Research Fellowship. SGV thanks ICMR for the research fellowship.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by CSIR-NCL Grant (MLP300326).