A nanodroplet cell processing platform facilitating drug synergy evaluations for anti-cancer treatments
Journal
Scientific Reports
Journal Volume
9
Journal Issue
1
Pages
10120
Date Issued
2019
Author(s)
Kuo, C.-T.
Wang, J.-Y.
Lu, S.-R.
Lai, Y.-S.
Hsieh, J.-T.
Wo, A.M.
Chen, B.P.C.
Lu, J.-H.
Abstract
Therapeutic drug synergism intervened in cancer treatments has been demonstrated to be more effective than using a single effector. However, it remains inherently challenging, with a limited cell count from tumor samples, to achieve potent personalized drug cocktails. To address the issue above, we herein present a nanodroplet cell processing platform. The platform incorporates an automatic nanodroplet dispenser with cell array ParaStamp chips, which were fabricated by a new wax stamping approach derived from laser direct writing. Such approach enables not only the on-demand de-wetting with hydrophobic wax films on substrates but also the mask-less fabrication of non-planar microstructures (i.e. no photolithography process). The ParaStamp chip was pre-occupied with anti-cancer drugs and their associate mixtures, enabling for the spatially addressable screening of optimal drug combinations simultaneously. Each droplet with a critical volume of 200 nl containing with 100 cells was utilized. Results revealed that the optimal combination reduces approximate 28-folds of conducted doses compared with single drugs. Tumor inhibition with the optimally selected drug combination was further confirmed by using PC-3 tumor-bearing mouse models. Together, the nanodroplet cell processing platform could therefore offer new opportunities to power the personalized cancer medicine at early-stage drug screening and discovery. ? 2019, The Author(s).
SDGs
Other Subjects
antineoplastic agent; baysilon; dimeticone; animal; devices; drug potentiation; drug screening; equipment design; high throughput screening; human; laser; male; miniaturization; nude mouse; procedures; Animals; Antineoplastic Combined Chemotherapy Protocols; Dimethylpolysiloxanes; Drug Screening Assays, Antitumor; Drug Synergism; Equipment Design; High-Throughput Screening Assays; Humans; Lasers; Male; Mice, Nude; Miniaturization; PC-3 Cells; Xenograft Model Antitumor Assays
Publisher
Nature Publishing Group
Type
journal article