Enhanced selective cytotoxicity of doxorubicin to breast cancer cells by methoxypolyethylene glycol conjugation via a novel beta-thiopropanamide linker

• Published in: European Polymer Journal
• Main Author: Supasena W.; Muangnoi C.; Praengam K.; Wong T.W.; Qiu G.; Ye S.; Wu J.; Tanasupawat S.; Rojsitthisak P.
• Format: Article
• Language: English
• Published: Elsevier Ltd 2020
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85092526437&doi=10.1016%2fj.eurpolymj.2020.110056&partnerID=40&md5=3a7f30d6e25c7ee9733a0e1c07b39d04

Doxorubicin (DOX) is a chemotherapeutic agent that suffers from severe adverse effects due to non-selective cell cytotoxicity. This study designs a novel beta-thiopropanamide linker (A) which conjugates DOX with methoxypolyethylene glycol (mPEG) to sustain systemic drug release, and to promote cancer enzyme-responsiveness and cell selectivity. The mPEG-DOX conjugate with the beta-thiopropanamide linker (P-A-DOX) conjugate was synthesized using thiol-functionalized methoxypolyethylene glycol and acrylic acid to establish the beta-thiopropanamide linkage with DOX, with the mPEG-DOX (P-DOX) conjugate as the control. The conjugates were structurally characterized by NMR, chemical assay, transmission electron microscopy and dynamic light scattering technique. The in vitro hydrolytic stability as a function of pH and cytotoxicity tests (MDA-MB-231 and MCF-7 breast cancer cells vs MCF-10A noncancerous cells) were performed. The P-A-DOX and P-DOX conjugates can self-assemble into nanoparticles. The P-A-DOX and P-DOX conjugates exhibited sustained drug release and improved physicochemical stability under physiological pHs. Their cancer cell cytotoxicity and selectivity progressed in the following order: P-A-DOX > P-DOX > DOX. The P-A-DOX conjugate with the beta-thiopropanamide linker is a selective DOX nanodelivery system for breast cancer treatment. © 2020 Elsevier Ltd