Development of aptamer conjugated quantum dots for detection of cancer
Abstract
Introduction: Cancer is one of the main life threatening diseases worldwide. Early detection of cancer using optical probes and biosensors as an emerging field of diagnostic medicine may address some challenging problems of cancer management.
Methods: To tackle the main technical hitches of cancer detection, we developed aptamer or antibody-conjugated quantum dot-based probes for fabrication of Mucin-based biosensor and optical probe. To develop an optical probe with theranostic capability, for the first time, (Mucin) aptamer-mitoxantrone-conjugated theranostic quantum dot (MTO-Apt-QD) was constructed for concurrent detection and therapy of cancer. After being synthesized, L-cystein capped quantum were conjugated with MUC-1 aptamer and then with mitoxantrone (MTO-Apt-QD). In vitro and in vivo imaging were performed for evaluation of pharmacodynamics and pharmacokinetics of these theranostic nanoparticles.
To prepare ultrasensitive biosensor for cancer detection, gold electrode was modified with mercaptopropionic acid (MPA), then consecutively conjugated with silica coated gold nanoparticles (AuNPs@SiO2), CdSe quantum dots (QDs) and anti CA-125 monoclonal antibody (mAb).
Results and discussion: The results indicated that MTO-Apt-QD nanoparticles could specifically target MUC-1 positive cancer cells. In the biosensor construction, Successive conjugation of AuNPs@SiO2, CdSe QD and anti CA-125 mAb onto the gold electrode resulted in sensitive detection of CA-125 with a limit of detection (LOD) of 0.0016 U/mL and linear detection range (LDR) of 0.002-0.1 U/mL.
Conclusion: Our novel aptameric detection and drug delivery system could concurrently image, specifically target and efficiently deliver the MTO loaded on the QDs to cancer cells. In addition, based on high sensitivity and low LOD of the immunosensor, we propose this highly stable and reproducible biosensor for detection of CA-125 at the early stage of the disease.