Design, Assembly, Characterization and Biological Applications of Biocompatible and Multifunctional 3D DNA Nanocages in Living Cells

The specificity of the interactions between complementary nucleotide bases can transform DNA into useful material for nanostructure construction through the design of specific nucleotide sequences. Self-assembled DNA nanostructures have defined shapes and are capable of targeted transportation of cargo within their structure and subsequent triggered release. Intracellular delivery of DNA nanostructure is commonly achieved through endocytosis. As yet, cellular uptake of DNA assemblies through endocytic pathway faces a major shortcoming due to localization inside acidic organelles such as lysosome and endosome, severely limiting the efficacy of intracellular targeting. Target-specific DNA nano-object can play a role in carrying and delivering a drug to the targeted cell as well as its area for disease treatment, giving rise to various biomedical applications such as diagnostics, therapeutics and drug delivery. Therefore, the development of novel biocompatible and multifunctional DNA nanostructures that show a specific targeting and drug or cargo delivery capability as well as a controllable release ability of cargo is of practical significance and has recently draw great attention. Towards these goals, we propose herein to rationally design and assemble novel multifunctional 3D DNA nanocages consisting of fluorescent markers for bio-imaging, targeting agents for cancer cells recognition as well as sub-cellular organelles localization, a well-designed cavity for selective encapsulation of guests and photoresponsive molecules for opening of cages in response to light. The chemical modification of DNA cages with active functional vectors/agents would facilitate specific tumor cell targeting and sub-cellular organelles localization without destroying their intrinsic behaviors. It is expected that a low cytotoxicity, high uptake efficiency and high stability of DNA nanocage are resulted. We also propose to systemically investigate the selective encapsulation of different molecular cargos, as well as explore the possibility of trigger-release of cargo in specific organelles under multi-photon laser light excitation. From both scientific and technological points of view, finding of this proposal strongly envision that multifunctional DNA nano-object will become one of the most intelligent nano-tool for in vitro or in vivo biomedical studies in respect to targeted drug delivery and cancer therapy.