Miu Shan Chan

Indole-based Cyanine as a Nuclear RNA-Selective Two-Photon Fluorescent Probe for Live Cell Imaging

We have demonstrated that the subcellular targeting properties of the indole-based cyanines can be tuned by the functional substituent attached onto the indole moiety in which the first example of a highly RNA-selective and two-photon active fluorescent light-up probe for high contrast and brightness TPEF images of rRNA in the nucleolus of live cells has been developed. It is important to find that this cyanine binds much stronger toward RNA than DNA in a buffer solution as well as selectively stains and targets to rRNA in the nucleolus. Remarkably, the TPEF brightness (Φσmax) is dramatically increased with 11-fold enhancement in the presence of rRNA, leading to the record high Φσmax of 228 GM for RNA. This probe not only shows good biocompatibility and superior photostability but also offers general applicability to various live cell lines including HeLa, HepG2, MCF-7, and KB cells and excellent counterstaining compatibility with commercially available DNA or protein trackers.

Nanoneedle‐Assisted Delivery of Site‐Selective Peptide‐Functionalized DNA Nanocages for Targeting Mitochondria and Nuclei

Peptide-functionalized DNA nano-objects selectively target mitochondria and the nucleus by means of nanoneedle-assisted delivery. This technology preserves the cell viability and structural integrity of nanostructures and assists the nano-objects in escaping degradation by endocytosis. This method opens up a new avenue for further in vitro studies of intracellular behaviors of DNA assemblies and their interactions in specific organelles.

A Reversible DNA Logic Gate Platform Operated by One- and Two-Photon Excitations.

We demonstrate the use of two different wavelength ranges of excitation light as inputs to remotely trigger the responses of the self-assembled DNA devices (D-OR). As an important feature of this device, the dependence of the readout fluorescent signals on the two external inputs, UV excitation for 1 min and/or near infrared irradiation (NIR) at 800 nm fs laser pulses, can mimic function of signal communication in OR logic gates. Their operations could be reset easily to its initial state. Furthermore, these DNA devices exhibit efficient cellular uptake, low cytotoxicity, and high bio-stability in different cell lines. They are considered as the first example of a photo-responsive DNA logic gate system, as well as a biocompatible, multi-wavelength excited system in response to UV and NIR. This is an important step to explore the concept of photo-responsive DNA-based systems as versatile tools in DNA computing, display devices, optical communication, and biology.

Mitochondrial Delivery of Therapeutic Agents by Amphiphilic DNA Nanocarriers.

The first example of mitochondrial delivery of the anticancer drug doxorubicin (Dox) is presented by lipid-functionalized DNA nanocages (LNCs). Dox localized in mitochondria induces significant cytotoxicity and cellular apoptosis in MCF-7 compared with Dox localized in lysosomes. These results suggest that LNC has the potential to be an outstanding tool in the treatment of specific organelle-related diseases such as cancers.

Cancer-Cell-Specific Mitochondria-Targeted Drug Delivery by Dual-Ligand-Functionalized Nanodiamonds Circumvent Drug Resistance

We demonstrate a nanotechnology approach for the development of cancer-cell-specific subcellular organelle-targeted drug nanocarriers based on photostable nanodiamonds (ND) functionalized with folic acid and mitochondrial localizing sequence (MLS) peptides. We showed that these multifunctional NDs not only distinguish between cancer cells and normal cells, and transport the loaded drugs across the plasma membrane of cancer cells, but also selectively deliver them to mitochondria and induce significant cytotoxicity and cell death compared with free Dox localized in lysosomes. Importantly, the cellular uptake of Dox was dramatically increased in a resistant model of MCF-7 cells, which contributed to the significant circumvention of P-glycoprotein-mediated drug resistance. Our work provides a novel method of designing nanodiamond-based carriers for targeted delivery and for circumventing drug resistance in doxorubicin-resistant human breast adenocarcinoma cancer cells.

Conformational Change of Self‐Assembled DNA Nanotubes Induced by Two‐Photon Excitation

Two-photon-regulated, shape-changing DNA nanostructures are demonstrated by integrating a DNA nanotube with a two-photon photocleavable module that enables the opening of the cavities of tube, and becomes partially single-stranded in response to two-photon excitation under 800 nm fs laser pulses.