Feedback System Control in Combinatorial Nanodiamond-based Drugs Optimization in vitro in Breast Cancer
Combinatorial drugs have been used for decades to improve therapeutic efficacy in cancer treatments through drug synergistic mediation. Although they are believed to have good efficiency in killing cancer cells by simultaneously suppress multi-drug resistance through targeting different cellular mechanisms, its remedial effects is still limited when considering heterogeneity of cancer cells. Recently, nanosystem-based agents have become new drug delivery systems to improve therapeutic efficiency as well as safeness. However, it is still difficult in optimizing desired effects combinations and fails to enhance drug efficacy efficiently. Thus, feedback system control (FSC) platform has been introduced to circumvent limitations in optimizing drug combinations for either unmodified or nanotechnology driven therapeutics. The FSC platform provides an algorithm that integrally and swiftly produces an ideal combination consisting of three nanodiamond-modified anticancer drugs: doxorubicin, mitoxantrone, bleomycin and one unmodified anticancer drug- paclitaxel. Particularly, the therapeutic windows obtained from the FSC-based nanodiamond-drug combinations were significantly higher than the ones in optimized unmodified drug combinations, single nanodiamond and unmodified drug administration, and randomly sampled nanodiamond-drug combination treatment. Moreover, the FSC methodology intrinsically considers cancer cell heterogeneity and sophisticated intracellular mechanisms. This approach can be potentially applied in optimizing multi-therapeutic systems clinically, expressing a favorable candidate in personalized medication development in the future.