Dual stimuli-responsive poly(succinyloxyethylmethacrylate-b-N-isopropylacrylamide) block copolymers as nanocarriers and respective application in doxorubicin delivery

ABSTRACT

Stimuli-responsive nanostructures were developed as anticancer drug delivery carriers. To this end, poly(2-hydroxyethylmethacrylate)-b-(N-isopropylacrylamide) (poly(HEMA-b-NIPAAm)) diblock copolymers were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization with two ratios remarked with (1) and (2). Based on gel permeation chromatography, the molecular weights of synthesized diblock copolymers were 17802 (1) and 13090 (2) g mol⁻¹. The pH- and thermoresponsive poly(succinyloxyethylmethacrylate-b-N-isopropylacrylamide) (poly)SEMA-b-NIPAAm)) diblock copolymers were obtained by reacting poly(HEMA-b-NIPAAm) with excess succinic anhydride in pyridine under mild conditions. Developed micelles with poly(SEMA-b-NIPAAm) (1) and poly(SEMA-b-NIPAAm) (2) diblock copolymers around pH of 3–4 at 25°C demonstrated the critical micelles concentrations (CMCs) of 0.026 and 0.019 g L⁻¹, respectively. The average sizes of poly)SEMA-b-NIPAAm) micelles using dynamic light scattering (DLS) measurements at pH 3.0, 6.0, and 9.0 were 240, 190, and 150 nm, respectively. The core-shell poly(SEMA-b-NIPAAm) micelles at pH 3 and 9 were 100–200 nm. The lower critical solution temperature (LCST) of poly)SEMA-b-NIPAAm) sample was determined to be 40°C by ultraviolet-visible (UV-vis) spectroscopy. The micelles of diblock copolymers were formed to enhance the drug solubility in aqueous solutions. Doxorubicin hydrochloride (DOX)-loading capacity was 99.1%. The release of DOX acted better at 42°C compared to 40°C. The results confirmed that pH- and temperature-dependent release of this drug carrier was particularly useful and important for the anticancer drug delivery at the tumor-like environment. Therefore, the biocompatibility of diblock copolymer was confirmed by assessing survival rate of breast cancer cell line (MCF7) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The synthesized nanoparticles would have an excellent potential as anticancer drug delivery.

GRAPHICAL ABSTRACT

KEYWORDS:

• Diblock copolymer
• drug delivery
• MTT assay
• nanocarrier
• RAFT polymerization
• stimuli-responsive

Acknowledgments

The authors express their gratitude to Payame Noor University for supporting the project.