Application of photopharmacology in agrochemicals

Photopharmacology is a novel technology in drug design that aims at solving poor drug selectivity.This technology is currently in the proof-of-concept phase and relies on the photoactivation or inactivation of photochromic ligands(PCLs)to regulate biological functions and living organisms.As potential molecular tools in future agriculture 4.0,the photochromic pesticides are effective in optical control of receptors,ion channels,living behaviors,and enzymes,which displays an innovative way of pesticide discovery.In this review,we highlight the progresses of the photoisomerized insecticides and fungicides.By integrating photoswitches,such as azobenzenes and diarylethenes,into pesticide molecules,several PCLs were developed for optical regulation of important insect or fungi targets in vivo,including GABARs,RyRs,nAChRs,SURs,sodium channels,GluCls,and SDH.The results are highly significant in revealing interactions of agrochemicals with their targets,biological functions,and living behaviors,and provide powerful toolkits in understanding ligand-receptor interactions.Moreover,there is a growing demand for a diverse range of PCLs,particularly those that are sensitive to red and NIR light or sunlight,for actual field use in agriculture.We envision that this particular mode of pesticide discovery is of great promise for overcoming the challenges posed by the improper use of agrochemicals.

Recent clinical trials and optical control as a potential strategy to develop microtubule-targeting drugs in colorectal cancer management

Colorectal cancer(CRC)has remained the second and the third leading cause of cancer-related death worldwide and in the United States,respectively.Although significant improvement in overall survival has been achieved,death in adult populations under the age of 55 appears to have increased in the past decades.Although new classes of therapeutic strategies such as immunotherapy have emerged,their application is very limited in CRC so far.Microtubule(MT)inhibitors such as taxanes,are not generally successful in CRC.There may be some way to make MT inhibitors work effectively in CRC.One potential advantage that we can take to treat CRC may be the combination of optical techniques coupled to an endoscope or other fiber optics-based devices.A combination of optical devices and photo-activatable drugs may allow us to locally target advanced CRC cells with highly potent MT-targeting drugs.In this Editorial review,we would like to discuss the potential of optogenetic approaches in CRC management.

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.

Light-responsive nanomedicine for cancer immunotherapy

Immunotherapy emerged as a paradigm shift in cancer treatments, which can effectively inhibit cancer progression by activating the immune system. Remarkable clinical outcomes have been achieved through recent advances in cancer immunotherapy, including checkpoint blockades, adoptive cellular therapy, cancer vaccine, and tumor microenvironment modulation. However, extending the application of immunotherapy in cancer patients has been limited by the low response rate and side effects such as autoimmune toxicities. With great progress being made in nanotechnology, nanomedicine has been exploited to overcome biological barriers for drug delivery. Given the spatiotemporal control,light-responsive nanomedicine is of great interest in designing precise modality for cancer immunotherapy. Herein, we summarized current research utilizing light-responsive nanoplatforms to enhance checkpoint blockade immunotherapy, facilitate targeted delivery of cancer vaccines, activate immune cell functions, and modulate tumor microenvironment. The clinical translation potential of those designs is highlighted and challenges for the next breakthrough in cancer immunotherapy are discussed.