Dick Yan Tam

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.

Multifunctional DNA nanomaterials for biomedical applications

The rapidly emerging DNA nanotechnology began with pioneer Seemans hypothesis that DNA not only can carry genetic information but also can be used as molecular organizer to create well-designed and controllable nanomaterials for applications in materials science, nanotechnology, and biology. DNA-based self-assembly represents a versatile system for nanoscale construction due to the well-characterized conformation of DNA and its predictability in the formation of base pairs. The structural features of nucleic acids form the basis of constructing a wide variety of DNA nanoarchitectures with well-defined shapes and sizes, in addition to controllable permeability and flexibility. More importantly, self-assembled DNA nanostructures can be easily functionalized to construct artificial functional systems with nanometer scale precision for multipurposes. Apparently scientists envision artificial DNA-based nanostructures as tool for drug loading and in vivo targeted delivery because of their abilities in selective encapsulation and stimuli-triggered release of cargo. Herein, we summarize the strategies of creating multidimensional self-assembled DNA nanoarchitectures and review studies investigating their stability, toxicity, delivery efficiency, loading, and control release of cargos in addition to their site-specific targeting and delivery of drug or cargo molecules to cellular systems.

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.

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.