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A Microfluidic Chip Integrated with Hyaluronic Acid-Functionalized Electrospun Chitosan Nanofibers for Specific Capture and Nondestructive Release of CD44-Overexpressing Circulating Tumor Cells
journal contribution
posted on 2018-02-07, 00:00 authored by Mengyuan Wang, Yunchao Xiao, Lizhou Lin, Xiaoyue Zhu, Lianfang Du, Xiangyang ShiDetection
of circulating tumor cells (CTCs) in peripheral blood
is of paramount significance for early-stage cancer diagnosis, estimation
of cancer development, and individualized cancer therapy. Herein,
we report the development of hyaluronic acid (HA)-functionalized electrospun
chitosan nanofiber (CNF)-integrated microfludic platform for highly
specific capture and nondestructive release of CTCs. First, electrospun
CNFs were formed and modified with zwitterion of carboxyl betaine
acrylamide (CBAA) via Michael addition reaction and then targeting
ligand HA through a disulfide bond. We show that the formed nanofibers
still maintain the smooth fibrous morphology after sequential surface
modifications, have a good hemocompatibility, and exhibit an excellent
antifouling property due to the CBAA modification. After being embedded
within a microfluidic chip, the fibrous mat can capture cancer cells
(A549, a human lung cancer cell line) with an efficiency of 91% at
a flow rate of 1.0 mL/h. Additionally, intact release of cancer cells
is able to be achieved after treatment with glutathione for 40 min
to have a release efficiency of 90%. Clinical applications show that
9 of 10 nonsmall-cell lung cancer patients and 5 of 5 breast cancer
patients are diagnosed to have CTCs (1 to 18 CTCs per mL of blood).
Our results suggest that the developed microfluidic system integrated
with functionalized CNF mats may be employed for effective CTCs capture
for clinical diagnosis of cancer.
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early-stage cancer diagnosis5 breast cancer patientsfunctionalized CNF matsHyaluronic Acid-Functionalized Electrospun Chitosan Nanofiberscancer cellsMichael addition reactionCD 44-Overexpressing Circulating Tumor Cells DetectionMicrofluidic Chip IntegratedCTClung cancer cell linecarboxyl betaine acrylamideHAsequential surface modificationsCBAA10 nonsmall-cell lung cancer patients
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