Chronic myeloid leukemia drug evaluation using a multisignal amplified photoelectrochemical sensing platform.
Chronic myeloid leukemia (CML) is a malignant clone disease of hematopoietic stem cells. At present, the most effective therapy for CML is bone marrow transplantation, but this procedure is expensive, and it is often difficult to find appropriately matched bone marrow donors. As an alternative to marrow transplantation, a more effective anticancer drug should be developed to cure the disease; in addition, an effective system to evaluate the activity of the drug needs to be developed. Herein, we present a novel antileukemia drug evaluation method based on a multisignal amplified photoelectrochemical sensing platform that monitors the activity of caspase-3, a known marker of cell apoptosis. Manganese-doped CdS@ZnS core-shell nanoparticles (Mn:CdS@ZnS) were synthesized via a simple wet chemical method, which provided a stable photocurrent signal. A DEVD-biotin peptide and streptavidin-labeled alkaline phosphatise (SA-ALP) were immobilized successively at these nanoparticles through amide bonding and through specific interaction between biotin and streptavidin, respectively. The photocurrent of this sensing platform improved as the ALP hydrolyzed the substrate 2-phospho-l-ascorbic acid (AAP) to ascorbic acid (AA), a more efficient electron donor. The activity of caspase-3 was detected using this sensing platform, and thus, the efficacy of nilotinib for targeting K562 CML cells could be evaluated. The results indicate that nilotinib can effectively induce apoptosis of the K562 cells. This sensing platform exhibited sensitive, reproductive, and stable performance in studying the nilotinib-induced apoptosis of K562 CML cells, and the platform could be utilized to evaluate other anticancer drugs.
State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry & Chemical Engineering, Nanjing University , Nanjing 210093, People's Republic of China.
Shiwei
S
Zhou
Yong
Y
Kong
Qingming
Q
Shen
Xiaolin
X
Ren
Jian-Rong
JR
Zhang
Jun-Jie
JJ
Zhu
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor / Q000295:instrumentation / Q000379:methods*; D055664:Electrochemical Techniques; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D055668:Photochemical Processes; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D011743:Pyrimidines; C498826:nilotinib