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|Title:||Tumor extracellular microenvironment responsive carbon dots for enhanced cancer theranostics||Authors:||Feng, Tao||Keywords:||DRNTU::Science::Chemistry::Biochemistry||Issue Date:||2017||Source:||Feng, T. (2017). Tumor extracellular microenvironment responsive carbon dots for enhanced cancer theranostics. Doctoral thesis, Nanyang Technological University, Singapore.||Abstract:||Cancer theranostics has been a rising field toward personalized cancer therapy for the benefit of patients through integrating bioimaging diagnostics with cancer treatment. Owing to the rapid advancement of nanotechnology, various theranostic nanoparticles have been developed, among which fluorescent carbon dots (CDs) are extraordinary nanomaterials because of their remarkable optical and biocompatible capabilities. So far, CDs have been extensively utilized as drug nanocarriers for chemotherapy drugs, photosensitizers, and therapeutic genes. However, these CDs often have insensitive surface properties, such as PEGylated, negatively or positively charged, or active targeting ligands attached on the surface, which cannot take full advantage of the difference between normal physiological condition and tumor microenvironment, leading to limited cancer therapeutic efficacy in vivo. To solve these problems and further promote the practical applications of CDs, in this thesis, tumor extracellular microenvironment responsive CDs were designed for enhanced cancer theranostics. Firstly, charge-convertible and anticancer prodrug-loaded CDs were prepared, which could undergo charge reversion from negative charge/PEGylation in physiological environment to positive charge under tumor extracellular condition. Thus, this nanocarrier possessed increased circulation half-life in blood, potent accumulation in the tumor area, facilitated internalization by cancer cells, enhanced escape from endosome, and reduction-triggered drug release, leading to low side effects and high tumor-inhibition efficacy toward carcinoma-bearing mice in contrast to the noncharge-convertible CDs. Secondly, tumor-triggered active-targeting and anticancer prodrug-loaded CDs were developed, which were PEGylated under physiological condition and exposed the inner targeting ligands in tumor extracellular microenvironment. Therefore, this nanocarrier could be uptaken efficiently by receptor-overexpressing cancer cells through specific ligand-receptor interaction, resulting in better therapeutic efficiency at tumor extracellular pH than that at physiological pH or against cancer cells with low receptor expression. Lastly, to better understand the activation of anticancer prodrug used in this thesis, fluorescence resonance energy transfer (FRET)-based CDs were designed. Upon anticancer prodrug activation under reductive conditions, the quenched blue fluorescence of CDs could be recovered while the unquenched green and red fluorescence of CDs was unaltered. Therefore, the gradually enhanced intensity ratio of blue-to-green or blue-to-red fluorescence could indicate the real-time reduction-responsive activation of anticancer prodrug in living cells. In summary, CDs with tumor extracellular microenvironment triggered charge-conversion or active-targeting capabilities have been successfully prepared for enhanced cancer therapy without appreciable side effects. Moreover, a CD-based ratiometric fluorescent sensor has also been developed to illustrate the intracellular activation mechanism of anticancer prodrug used in above systems. Therefore, these designs can offer promising chances to create safe and effective CD-based theranostic agents for potential anticancer applications.||URI:||http://hdl.handle.net/10356/72895||DOI:||10.32657/10356/72895||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
|Appears in Collections:||SPMS Theses|
Updated on May 14, 2021
Updated on May 14, 2021
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