Photosensitive drug delivery systems for cancer therapy: Mechanisms and applications.

Over the past three decades, various photosensitive nanoparticles have been developed as potential therapies in human health, ranging from photodynamic therapy technologies that have already reached clinical use, to drug delivery systems that are still in the preclinical stages. Many of these systems are designed to achieve a high spatial and temporal on-demand drug release via phototriggerable mechanisms. This review examines the current clinical and experimental applications in cancer treatment of photosensitive drug release systems, including nanocarriers such as liposomes, micelles, polymeric nanoparticles, and hydrogels. We will focus on the three main physicochemical mechanisms of imparting photosensitivity to a delivery system: i) photochemical reactions (oxidation, cleavage, and polymerization), ii) photoisomerization, iii) and photothermal reactions. Photosensitive nanoparticles have a multitude of different applications including controlled drug release, resulting from physical/conformational changes in the delivery systems in response to light of specific wavelengths. Most of the recent research in these delivery systems has primarily focused on improving the efficacy and safety of cancer treatments such as photodynamic and photothermal therapy. Combinations of multiple treatment modalities using photosensitive nanoparticulate delivery systems have also garnered great interest in combating multi-drug resistant cancers due to their synergistic effects. Finally, the challenges and future potential of photosensitive drug delivery systems in biomedical applications is outlined.

Latest Evidence Regarding the Effects of Photosensitive Drugs on the Skin: Pathogenetic Mechanisms and Clinical Manifestations.

Photosensitivity induced by drugs is a widely experienced problem, concerning both molecule design and clinical practice. Indeed, photo-induced cutaneous eruptions represent one of the most common drug adverse events and are frequently an important issue to consider in the therapeutic management of patients. Phototoxicity and photoallergy are the two different pathogenic mechanisms involved in photosensitization. Related cutaneous manifestations are heterogeneous, depending on the culprit drug and subject susceptibility. Here we report an updated review of the literature with respect to pathogenic mechanisms of photosensitivity, clinical manifestations, patient management, and prediction and evaluation of drug-induced photosensitivity. We present and discuss principal groups of photosensitizing drugs (antimicrobials, nonsteroidal anti-inflammatory drugs, anti-hypertensives, anti-arrhythmics, cholesterol, and glycemia-lowering agents, psychotropic drugs, chemotherapeutics, etc.) and their main damage mechanisms according to recent evidence. The link between the drug and the cutaneous manifestation is not always clear; more investigations would be helpful to better predict drug photosensitizing potential, prevent and manage cutaneous adverse events and find the most appropriate alternative therapeutic strategy.

CB1-Antibody Modified Liposomes for Targeted Modulation of Epileptiform Activities Synchronously Detected by Microelectrode Arrays.

Temporal lobe epilepsy (TLE) is a focal, recurrent, and refractory neurological disorder. Therefore, precisely targeted treatments for TLE are greatly needed. We designed anti-CB1 liposomes that can bind to CB1 receptors in the hippocampus to deliver photocaged compounds (ruthenium bipyridine triphenylphosphine γ-aminobutyric acid, RuBi-GABA) in the TLE rats. A 16-channel silicon microelectrode array (MEA) was implanted for simultaneously monitoring electrophysiological signals of neurons. The results showed that anti-CB1 liposomes were larger in size and remained in the hippocampus longer than unmodified liposomes. Following the blue light stimulation, the neural firing rates and the local field potentials of hippocampal neurons were significantly reduced. It is indicated that RuBi-GABA was enriched near hippocampal neurons due to anti-CB1 liposome delivery and photolyzed by optical stimulation, resulting dissociation of GABA to exert inhibitory actions. Furthermore, K-means cluster analysis revealed that the firing rates of interneurons were decreased to a greater extent than those of pyramidal neurons, which may have been a result of the uneven diffusion of RuBi-GABA due to liposomes binding to CB1. In this study, we developed a novel, targeted method to regulate neural electrophysiology in the hippocampus of the TLE rat using antibody-modified nanoliposomes, implantable MEA, and photocaged compounds. This method effectively suppressed hippocampal activities during seizure ictus with high spatiotemporal resolution, which is a crucial exploration of targeted therapy for epilepsy.

Glutathione S-transferase polymorphisms in patients with photosensitive and non-photosensitive drug eruptions.

BACKGROUND: Glutathione S-transferases (GSTs) play a critical role in cellular protection against oxidative damage. Polymorphisms in three major GST loci have been described. A number of studies have looked for an association between GSTs and skin diseases. PURPOSE: To ascertain the possibility that polymorphisms in the GSTM1, GSTT1, and GSTP1 genes may predict the development of photo-induced and non-photo-induced drug eruptions. METHODS: A cohort of 40 patients with drug eruptions, 10 of whom had developed a photo-induced drug reaction, and matched controls (116 for GSTM1 and GSTT1, 120 for GSTP1) were studied. Genotyping was conducted using direct sequencing and polymerase chain reaction. RESULTS: The GSTP1 Val/Val genotype was significantly associated with non-photosensitive drug eruptions (OR = 3.64, P value = 0.038), whereas associations observed between GSTP1, GSTM1, GSTT1 polymorphisms and photosensitive drug eruptions did not reach statistical significance. CONCLUSIONS: Variations in GSTP1 may affect the risk to develop non-photo-induced drug eruptions. These results warrant confirmatory studies in a larger patient sample.

Application of BODIPY for tooth whitening as a photosensitive drug / 国际生物医学工程杂志

Objective To study the tooth whitening effect of boron-dipyrromethene (BODIPY) as a photosensitive drug combining photodynamic therapy (PDT) and the influence on the surface of the enamel.Methods After oxidation of hydrogen peroxide or BODIPY by photodynamic therapy,the extracted teeth were evaluated by Vita shade guides matching.The change of surface enamel on the crystals and microstructure was observed by scanning electron microscopy (SEM).Results The teeth treated with BODIPY by PDT were smooth and whitened with the remineralization of teeth surface in morphology.While the teeth treated with hydrogen peroxide were whitened obviously but the surface morphology of the teeth was demineralized seriously.Conclusion The results suggest that PDT is effective for teeth whitening and can promote the remineralization of teeth surface enamel with BODIPY as a photosensitive drug.PDT is expected to become a new method for tooth whitening.