Design and synthesis of small molecules and nanoparticle conjugates for cell type-selective delivery
Chen, Po Chih
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Histone deacetylase (HDAC) inhibition is an emerging novel therapeutic strategy in cancer therapy. HDAC inhibitors (HDACi) have shown ability to block angiogenesis and cell cycling, as well as initiate differentiation and apoptosis. In fact, suberoylanilide hydroxamic acid (SAHA) is the first in the class of HDACi approved by the FDA for the treatment of cutaneous T cell lymphoma. On the other hand, there is a sustained interest in the use of gold nanoparticles (AuNPs) for various cancer diagnostic and therapeutic applications - bioimaging, drug delivery, and binary therapy techniques such as photodynamic and photothermal therapies. This interest in AuNPs is facilitated by favorable attributes such as ease of fabrication, bioconjugation and biocompatibility, and unique optical and electronic properties. However, HDACi- and AuNPs- based antitumor agents are plagued with problems common to all chemotherapeutic agents such as lack of selectivity, which often results in systemic toxicity. Therefore, availability of a methodology to selectively deliver AuNPs and HDACi to cancer cells will significantly improve their therapeutic indices and lead to the identification of novel agents for use in diagnostic imaging and targeted cancer therapy applications.