RESUMEN
Telomerase is regarded as a crucial biomarker for the early diagnosis of malignant tumors and a valuable therapeutic target. In this work, a telomerase-triggered amplification strategy was designed on the basis of a catalyzed hairpin assembly (CHA) for bridging a signal probe of platinum nanoparticles (Pt NPs) anchored on three-dimensional (3D) epoxy-functionalized macroporous carbon (Pt/MPC-COOH) in an ultrasensitive electrochemical biosensor. Pt/MPC-COOH nanomaterials with interconnected macroporous structure not only immobilized hairpin DNA probe 2 (H2) via an amide reaction (Pt/MPC-COOH-H2), but they also generated an obvious electrochemical signal in response to acetaminophen (AP) oxidation. After the introduction of telomerase, telomerase primer (TP) was extended to a telomerase extension product (TEP) with several hexamer repeats (TTAGGG)n to initiate the CHA cycle, leading to signal amplification. Subsequently, with the TEP-triggered CHA cycle amplification strategy, a large amount of Pt/MPC-COOH-H2 was introduced on the electrode surface for the construction of the electrochemical platform, which realized the sensitive detection of telomerase activity from 102 to107 cells mL-1 with a limit of detection (LOD) of 9.02 cells mL-1. This strategy provides a sensitive method for the detection of biomolecules that could be useful for bioanalysis and early clinical diagnoses of diseases.
Asunto(s)
Técnicas Biosensibles , Nanopartículas del Metal , Telomerasa , Carbono , Catálisis , Técnicas Electroquímicas , Límite de Detección , Platino (Metal) , Telomerasa/metabolismoRESUMEN
Although considerable clinical attempts on various kinds of cancers have been made, photodynamic therapy (PDT) still suffers from attenuated therapeutic effects because of the developed resistance of cancer cells. As a novel antiapoptosis protein, survivin has been demonstrated to be selectively overexpressed in a great number of human malignancies and plays a significant part in cancer progression and therapeutic resistance. Herein, we present an upconversion nanoplatform for enhanced PDT by DNAzyme-mediated gene silencing of survivin. In our system, a long single-stranded DNA (ssDNA) with a repetitive aptamer (AS1411) and survivin-targeted DNAzyme was fabricated by rolling circle amplification (RCA) and adsorbed on the upconversion nanoparticles (UCNPs) by electrostatic attraction. The multivalence of the ssDNA endows the upconversion nanoplatform with high recognition and loading capacity of photosensitizers and DNAzymes. When the nanoplatform is targeted internalized into cancer cells, PDT can be triggered by near-infrared (NIR) light to generate reactive oxygen species (ROS) for killing the cancer cells. Moreover, the encoded DNAzyme can efficiently inhibit the gene expression of survivin, providing the potential to enhance the efficiency of PDT. This study thus highlights the promise of an upconversion photodynamic nanoplatform for admirable combination therapy in cancer.