3D stem-like spheroids-on-a-chip for personalized combinatorial drug testing in oral cancer

Functional drug testing (FDT) with patient-derived tumor cells in microfluidic devices is gaining popularity. However, the majority of previously reported microfluidic devices for FDT were limited by at least one of these factors: lengthy fabrication procedures, absence of tumor progenitor cells, la...

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Bibliographic Details
Published in:Journal of nanobiotechnology 2024-06, Vol.22 (1), p.344-18
Main Authors: Mehta, Viraj, Vilikkathala Sudhakaran, Sukanya, Nellore, Vijaykumar, Madduri, Srinivas, Rath, Subha Narayan
Format: Article
Language:English
Subjects:
3D printing
Analysis
Antimitotic agents
Antineoplastic agents
Antineoplastic Agents - pharmacology
Cancer
Care and treatment
Chemotherapy
Combinatorial drug testing
Diagnosis
DNA sequencing
Drug Screening Assays, Antitumor - methods
Drug therapy
Ethylenediaminetetraacetic acid
Fluorouracil - pharmacology
Functional drug testing
Head and neck cancer
Humans
Integrated circuits
Lab-On-A-Chip Devices
Microfluidics
Molecular dynamics
Mouth cancer
Mouth Neoplasms - drug therapy
Mouth Neoplasms - pathology
Neoplastic Stem Cells - drug effects
Nucleotide sequencing
Paclitaxel - pharmacology
Personalized medicine
Precision Medicine - methods
Printing, Three-Dimensional
Semiconductor chips
Spheroids, Cellular - drug effects
Spheroids-on-chips
Squamous cell carcinoma
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Summary:Functional drug testing (FDT) with patient-derived tumor cells in microfluidic devices is gaining popularity. However, the majority of previously reported microfluidic devices for FDT were limited by at least one of these factors: lengthy fabrication procedures, absence of tumor progenitor cells, lack of clinical correlation, and mono-drug therapy testing. Furthermore, personalized microfluidic models based on spheroids derived from oral cancer patients remain to be thoroughly validated. Overcoming the limitations, we develop 3D printed mold-based, dynamic, and personalized oral stem-like spheroids-on-a-chip, featuring unique serpentine loops and flat-bottom microwells arrangement. This unique arrangement enables the screening of seven combinations of three drugs on chemoresistive cancer stem-like cells. Oral cancer patients-derived stem-like spheroids (CD 44 ) remains highly viable (> 90%) for 5 days. Treatment with a well-known oral cancer chemotherapy regimen (paclitaxel, 5 fluorouracil, and cisplatin) at clinically relevant dosages results in heterogeneous drug responses in spheroids. These spheroids are derived from three oral cancer patients, each diagnosed with either well-differentiated or moderately-differentiated squamous cell carcinoma. Oral spheroids exhibit dissimilar morphology, size, and oral tumor-relevant oxygen levels (
ISSN:1477-3155
1477-3155
DOI:10.1186/s12951-024-02625-y