In vitro study of doxorubicin-loaded thermo- and pH-tunable carriers for targeted drug delivery to liver cancer cells

• Published in: Journal of industrial and engineering chemistry (Seoul, Korea) Vol. 104; pp. 93 - 105
• Main Authors: Kunene, Sikhumbuzo Charles, Lin, Kuen-Song, Weng, Meng-Tzu, Carrera Espinoza, Maria Janina, Wu, Chun-Ming
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 25.12.2021; 한국공업화학회
• Subjects: Doxorubicin; Magnetic graphene nanosheet; Nanogel; Stimulus-dependent; Thermo- and pH-dependent carrier; 화학공학; Thermo- and pH-dependent carrier; Magnetic graphene nanosheet; Nanogel; Stimulus-dependent; Doxorubicin
• ISSN: 1226-086X; 1876-794X
• DOI: 10.1016/j.jiec.2021.08.012

[Display omitted] •Dual thermo- and pH-dependent carriers were successfully synthesized.•The as-synthesized carriers were nontoxic against HEK293T and HepG2 cells.•The MTT showed an enhanced efficacy of the DOX released with AMF.•The released profiles showed faster DOX release above LCST and in acidic pH.•Intracellular intake of the formulations was proposed and confirmed. In this study, a series of thermo- and pH-dependent doxorubicin (DOX) carriers based on magnetic graphene nanosheets (MGNSs), functionalized by poly(N-isopropylacrylamide) (PNIPAM) and polyethylenemine (PEI) nanogel, targeting liver cancer cells were formulated. The temperature phase transitions of the carriers can be tuned as a function of pH to the intended value in the range of 38–42 °C. In vitro studies showed a high cell viability of above 90% at all doses of MGNSs and MGNS-nanogel against HEK293T normal and HepG2 cancerous cells, confirming the biocompatibility and nontoxicity of the carriers. In comparison, the MGNS-nanogel-DOX demonstrated a sufficient therapeutic effect towards HepG2 cell line. The cell viability results showed enhanced efficacy of the drug released by means of applied magnetic field (AMF). Moreover, an efficient cellular intake of the carriers into the HepG2 cells was achieved. Additionally, the achieved low DOX release at a lower temperature and neutral pH can retain the drug in the carriers until reaching the targeted sites. Nevertheless, the high drug release showed that the release was triggered by high temperature and acidic pH. Hence, the developed thermo- and pH-tunable MGNS-nanogel-DOX showed a high potential for microenvironment stimulus-prompted drug delivery and cancer cell suppression.