A Nanocomposite System For Protease Detection And Combined Photothermal-chemotherapy

In order to improve the efficiency of cancer therapy, timely diagnosis and effective treatment are the two key factors for tumor treatment, but the current commonly used diagnosis technology and treatment methods have certain limitations. Nanomaterials such as gold nanoparticles(Au NPs), quantum dots(QDs) and graphene oxide(GO) can be used to develop higher effective technology for tumor diagnosis and therapy, owning to their unique physical and chemical properties. The biomedical probes based on nanomaterials are able to be used for early tumor diagnosis by biological molecules such as protease detection. The multifunctional nanocomposite can combine different treatment methods into a single platform for comprehensive treatment of tumor, which improve the effect of treatment and reduce the side effects efficiently compared to the single therapy. In this thesis we successfully prepared the nanocomposites which have great potential in both protease detection and combined photothermal-chemotherapy. The main content is as follows:1. We built a fluorescent probe for the highly sensitive detection of caspase-3 activities on the basis of the inner-filter effect(IFE) of Au NPs on Cd Te QDs. When labeled with a peptide possessing the caspase-3 cleavage sequence(DEVD), the monodispersed Au-Ps(peptide-modified Au NPs) exhibited a tendency to aggregate when exposed to caspase-3, which induced the absorption band transition from 520 to 680 nm and turned on the fluorescence of the Cd Te QDs for caspase-3 sensing. Under optimum conditions, a high sensitivity towards caspase-3 was achieved with a detection limit as low as 18 p M, which was much lower than the corresponding assays based on absorbance or other approaches.2. We successfully integrated a Pt(IV) complex, PEGylated nano-graphene oxide(PEG-NGO), and a cell apoptosis sensor into a single platform to generate a multifunctional nanocomposite(PEG-NGO-Pt) which shows potential for targeted drug delivery and combined photothermal-chemotherapy under near infrared laser irradiation(NIR), and real-time monitoring of its therapeutic efficacy. Non-invasive imaging using a fluorescent probe immobilized on the GO shows an enhanced therapeutic effect of PEG-NGO-Pt in cancer treatment via apoptosis and cell death. Due to the enhanced cytotoxicity of cisplatin and the highly specific tumor targeting of PEG-NGO-Pt at elevated temperatures, this nanocomposite displays a synergistic effect in improving the therapeutic efficacy of the Pt drug with complete destruction of tumors, no tumor recurrence and minimal systemic toxicity in comparison with chemotherapy or photothermal treatment alone.In summary, we designed a multifunctional nanocomposite system for tumor diagnosis and therapy based on the nanomaterials after different modifications, which exhibited high sensitivety towards caspase-3 and improved therapeutic efficacy in cancer treatment. Our work enriched the study for build-up of novel nanomaterials in protease detection and cancer therapy, which has potential application in the clinical diagnosis and treatment of tumor.