A Novel Photocleaver with Long Wavelength Absorption-Highly Efficient Antitumor Agent: 4-(2-Diethylamino-ethylamino)-8-oxo-8H-acenaphtho-[1,2-b]pyrrole-9-carbonitrile

The photocleavage abilities of a novel family of compounds, 8-oxo-8%H%-acenaphtho pyrrole-9-carbonitrile and its derivatives(compounds 1—5) were evaluated with M13 mp18 single strand circular DNA. Only compound 1 with a diethylamine group could bind to DNA %via% electrostatic attraction and intercalation. At a concentration of 50 μmol/L, it could generate singlet oxygen to cleave circular DNA into linear DNA under the irradiation of long wavelength light(λ>400 nm). The antitumor {ability} of compound 1 was also evaluated in vitro, and its IC_ 50 on HeLa cells was as low as 6.8 μmol/L.

Towards medical imaging of drug photoactivation:Development of light responsive magnetic resonance imaging and chemical exchange saturation transfer contrast agents

In recent years,the use of light to selectively and precisely activate drugs has been developed along the fundamental concepts of photopharmacology.One of the key methods in this field relies on transiently silencing the drug activity with photocleavable protecting groups(PPGs).To effectively utilize light-activated drugs in future medical applications,physicians will require a reliable method to assess whether light penetrates deep enough into the tissues to activate the photoresponsive theragnostic agents.Here,we describe the development and evaluation of magnetic resonance(MR)imaging agents that allow for the detection of light penetration and drug activation in the tissues using non-invasive whole-body magnetic resonance imaging(MRI)and chemical exchange saturation transfer(CEST)-MRI modalities.The approach relies on the use of PPG-protected MR contrast agents,which upon irradiation with light change their imaging signal.A Gadolinium(III)-based MRI contrast agent is presented that undergoes a significant change in relaxivity(25%)upon uncaging,providing a reliable indicator of lightinduced cargo release.Additionally,we introduce the first light-responsive CESTMRI imaging agent,enabling positive signal enhancement(off-to-on)upon light activation,offering a novel approach to visualize the activation of photoactive agents in living tissues.This research provides a proof-of-principle for the noninvasive,whole-body imaging of light penetration and drug activation with high temporal resolution characteristic of MR methods.

Recent progresses on the development of thioxo-naphthalimides

Thioxo/dithioxo-naphthalimide is a class of rarely visited fluorophore,first synthesized in 1999.Facile chemistry was devised to achieve mono or dual thionation of the two carbonyl groups of 1,8-naphthalimide.Thionation effectively shifts absorption maximum to longer spectral wavelength,significantly increase absorption coefficients,and dramatically enhances intersystem crossing efficiency with respect to their oxo-analogues.They were first explored as potent photocleavers to induce DNA strand break and novel photosensitizers for photodynamic therapies.In recent years,the unique chemistry of thioxo groups has been harnessed to achieve new applications,such as fluorescent sensors for heave metal ions.These unique photochemical and photophysical characteristics revitalize them intriguing functional molecules to investigate.In this short review,we wish to revisit their first discovery,facile synthesis,and the endeavors on the use of thioxo/dithioxo-naphthalimides for novel chemical and biomedical applications.

Phototriggered targeting of nanocarriers for drug delivery

Stimuli-triggered targeting of drug delivery systems can both increase the therapeutic efficacy and lower toxicity by selectively delivering drugs at target sites with high specificity and efficiency. Light is a convenient and powerful stimulus for use in such drug delivery systems because it is readily available and noninvasive and offers excellent spatiotemporal control. The power and wavelength of light can be finely tuned for different photoresponsive systems to achieve efficient targeting at the tissue, cellular, or subcellular levels. Here, we have reviewed the various mechanisms for phototriggered targeting （phototargeting） of drug nanocarriers. We have discussed the three main phototargeting strategies： （1） targeting ligand activation; （2） particle size reduction; and （3） blood vessel disruption.

A novel o-nitrobenzyl-based photocleavable antitumor prodrug with the capability of releasing 5-fluorourail

An o-nitrobenzyl-based photocleavable antitumor prodrug with a terminal carboxyl group was designed and synthesized.The photolysis properties of the prodrug were investigated by means of1H NMR,HPLC,UV,and MTT methods.The results showed that the toxicity of the anticancer drug was effectively shielded before release.However,the prodrug effectively regained the antitumor capability against cancer cells by release of 5-fluorouracil when it was exposed to ultraviolet irradiation.

Engineering Photocleavable Protein-decorated Hydrogels to Regulate Cell Adhesion and Migration

Cell adhesion and migration play essential roles in tissue development and maintenance, and abnormal cell migration is involved in life-threatening diseases, including vascular disease, tumor formation, and metastasis. The advances in hydrogel-based 3D cell culture development facilitated the investigation of cell motility behavior, including cell-cell and cell-matrix adhesion and cell migration in a microenvironment more related to in vivo situations. Establishing advanced methods for these in vitro studies is thus necessary. Photo-sensitive proteins show advantages in remote and non-invasive regulation of hydrogels’ properties, and thus are of great potential in regulating 3D cultured cells’ behavior. In the presented study, we engineered photocleavable protein(PhoCl)-decorated hydrogels to regulate cell adhesion and migration of MDA-MB-231. The integrin-binding motif RGD was fused to the PhoCl and was decorated on the hydrogel. After being exposed to light at 405 nm, the PhoCl was cleaved and the RGD motif was released, resulting in detachment of the binding cells. The regulatory effect of the light illumination showed a time-dependent and cell density-dependent manner. Furthermore, the elimination of RGD by patterned light exposure completely suspended the cell migration to the corresponding region, suggesting a controllable regulation of the cell migration direction.

A Cell-Anchored and Self-Calibrated DNA Nanoplatform for in Situ Imaging and Quantification of Endogenous MicroRNA in Live Cells:Introducing Two Controls to Normalize the Sensing Signals

Quantifying the microRNAs(miRNAs)levels in living cells,while essential for the study of fundamental biology and medical diagnostics,has barely been achieved due to insufficient probe delivery and unquantifiable signals.We report a cell-anchored and self-calibrated DNA nanoplatform,a cholesterol-headed DNA nanowire that is capable of efficiently delivering to various cells and simultaneously detecting two target miRNAs.One miRNA target can be utilized as an endogenous control against cell-to-cell variations.Moreover,the photocleavable linkers inserted in the nanostructures allow us to precisely regulate the probe structure and fluorescence signaling at the desired time and location in vivo.As a second control,the maximum fluorescence can be elicited by UV light,which further facilitates the normalization of the absolute fluorescence signal.With two introduced internal controls,the maximum fluorescence and endogenous control gene,this approach displays excellent stability and self-calibration performance,effectively avoiding the interference from operating conditions and cellto-cell variations,such as the laser powers and intracellular probe concentrations.Importantly,this design is capable of unifying the output signal intensity between in vitro test and cell imaging,making the in vitro linear calibration curve appropriate for the quantification of miRNA expression in living cells.