Multifunctional DNA Nanoflower Applied for High Specific Photodynamic Cancer Therapy In Vivo.

Photodynamic therapy (PDT) is a newly emerged strategy for disease treatment. One challenge of the application of PDT drugs is the side-effect caused by the non-specificity of the photosensitive molecules. Most of the photosensitizers may invade not only the pathogenic cells but also the normal cells. In recent, people tried to use special cargoes to deliver the drugs into target cells. DNA nanoflowers (NFs) are a kind of newly-emerged nanomaterial which constructed through DNA rolling cycle amplification (RCA) reaction. It is reported that the DNA NFs were suitable materials which have been widely applied as nanocargos for drug delivery in cancer chemotherapeutic treatment. In this paper, we have introduced a new multifunctional DNA NF which could be prepared through an one-pot RCA reaction. This proposed DNA NF contained a versatile AS1411 G-quadruplex moiety, which plays key roles not only for specific recognition of cancer cells but also for near-infrared ray based photodynamic therapy when conjugating with a special porphyrin molecule. We demonstrated that the DNA NF showed good selectivity toward cancer cells, leading to highly efficient photo-induced cytotoxicity. Moreover, the in vivo experiment results suggested this DNA NF is a promising nanomaterial for clinical PDT.

Chiral Interaction Is a Decisive Factor To Replace d-DNA with l-DNA Aptamers.

Nucleic acid aptamers have been widely used in various fields such as biosensing, DNA chip, and medical diagnosis. However, the high susceptibility of nucleic acids to ubiquitous nucleases reduces the biostability of aptamers and limits their applications in biological contexts. Therefore, improving the biostability of aptamers becomes an urgent need. Herein, we present a simple strategy to resolve this problem by directly replacing the d-DNA-based aptamers with left-handed l-DNA. By testing several reported aptamers against respective targets, we found that our proposed strategy stood up well for nonchiral small molecule targets (e.g., Hemin and cationic porphyrin) and chiral targets whose interactions with aptamers are chirality-independent (e.g., ATP). We also found that the l-DNA aptamers were indeed endowed with greatly improved biostability due to the extraordinary resistance of l-DNA to nuclease digestion. With respect to other small-molecule targets whose interactions with aptamers are chirality-dependent (e.g., kanamycin) and biomacromolecules (e.g., tyrosine kinase-7), however, the proposed strategy was not entirely effective likely due to the participation of the DNA backbone chirality into the target recognition. In spite of this limitation, this strategy indeed paves an easy way to screen highly biostable aptamers important for the applications in many fields.

pH-Controlled Intracellular in Situ Reversible Assembly of a Photothermal Agent for Smart Chemo-Photothermal Synergetic Therapy and ATP Imaging.

To advance anti-tumor efficiency and lessen the adverse effect caused by nanodrug residues in the body, a smart nanoagent system is developed and successfully used in intracellular ATP imaging and in vivo chemo-photothermal synergetic therapy. The nanoagent system is facilely prepared using a DNA complex to modify gold nanoparticles (AuNPs). The DNA complex is formed by three oligonucleotides (ATP aptamer, rC-DNA, and rG-DNA). The CG-rich structure in a ternary DNA complex could be exploited for payload of chemotherapeutic medicine doxorubicin (DOX), thus making efficient DOX transport into the tumor site possible. In tumor cells, especially in acidic organelles (e.g., endosome and lysosome), DOX could be rapidly released via the dual stimuli of overexpressed ATP and pH. What is more, the specific recognition of a fluorescently labeled aptamer strand to ATP can achieve the intracellular ATP imaging. pH-controlled reversible folding and unfolding of intermolecular i-motif formed by C-rich strands can lead to intracellular in situ assembly of AuNP aggregates with high photothermal conversion efficiency and promote relatively facile renal clearance of AuNPs through the disassociation of the aggregates in extracellular environments. Experiments in vivo and vitro present feasibility for a synergetic chemo-photothermal therapy. Such an in situ reversible assembly strategy of a chemo-photothermal agent also presents a new paradigm for a smart and highly efficient disease treatment with reduced side effects.