Self-amplified activatable nanophotosensitizers for HIF-1α inhibition-enhanced photodynamic therapy.

Activatable photodynamic therapy (PDT) has shown great potential in cancer therapy owing to its high tumor specificity and minimized side effect. However, the relatively low level of biomarkers within tumor tissue rescricts the photosensitizer to get thoroughly activated. In this study, we design a self-amplified activatable nanophotosensitizer (CPPa NP) for enhanced PDT. CPPa NP is prepared by encapsulating a hypoxia-inducible factor 1α (HIF-1α) inhibitor CI-994 with an amphiphilic hydrogen peroxide (H2O2) responsive copolymer PPa-CA-PEG. Upon the addition of H2O2, the thioketal linker within CPPa NP is cleaved, resulting in the simultaneous release of thiol-modified pyropheophorbide a (PPa-SH), cinnamic aldehyde (CA), and CI-994. PPa-SH can be encapsulated by albumin to turn on its photodynamic efficiency, while CI-994 may inhibit the expression of HIF-1α to improve the PDT efficacy. CA is able to deplete glutathione (GSH) and upregulate reactive oxygen species (ROS) within tumor cells, accelerating the dissociation of nanoparticles and disrupting the redox balance of tumor cells. In vitro and in vivo studies showed that CPPa NP can successfully elevate the ROS level within 4T1 cells and has a better anticancer efficacy than PPa NP without CI-994 under laser irradiation. This study thus provides an effective approach to develop self-amplified activatable nanoparticles for enhanced PDT.

Evaluating proxies for motion sickness in rodent.

Motions sickness (MS) occurs when the brain receives conflicting sensory signals from vestibular, visual and proprioceptive systems about a person's ongoing position and/or motion in relation to space. MS is typified by symptoms such as nausea and emesis and implicates complex physiological aspects of sensations and sensorimotor reflexes. Use of animal models has been integral to unraveling the physiological causality of MS. The commonly used rodents (rat and mouse), albeit lacking vomiting reflex, reliably display phenotypic behaviors of pica (eating of non-nutritive substance) and conditioned taste aversion (CTAver) or avoidance (CTAvoi) which utilize neural substrates with pathways that cause gastrointestinal malaise akin to nausea/emesis. As such, rodent pica and CTAver/CTAvoi have been widely used as proxies for nausea/emesis in studies dealing with neural mechanisms of nausea/emesis and MS, as well as for evaluating therapeutics. This review presents the rationale and experimental evidence that support the use of pica and CTAver/CTAvoi as indices for nausea and emesis. Key experimental steps and cautions required when using rodent MS models are also discussed. Finally, future directions are suggested for studying MS with rodent pica and CTAver/CTAvoi models.