Combined therapy now plays a major role in cancer therapy due to the outcome of huge amounts of scientific experiments in recent years. However, all systems designed previously have been unable to simultaneously deliver therapy effects using several methods to produce a greater overall therapeutic effect. To solve the problem, we constructed a delivery system of near-infrared light (NIR)-triggered reactive oxygen species (ROS)-sensitive nanoparticles (NPs) for simultaneous chemotherapy and photodynamic therapy (PDT). The inner NP was assembled from a hydrophobic upconverting nanoparticle (UCN) core, with a thin silica shell linked with rose bengal (RB). Finally, a type of ROS-induced biodegradable polymer named poly-(1, 4-phenyleneacetone dimethylenethioketal) (PPADT) was self-assembled to form the NP as an outer shell to load the inner NP and doxorubicin (DOX). As the results show, the UCN core works as a transducer to convert deeply penetrating NIR to visible light for activating the photosensitizer RB for PDT under NIR excitation. In the meantime, the redundant ROS caused PPADT to biodegrade to release the loaded DOX, realizing simultaneous chemotherapy and PDT. Properties such as structure, size distribution, morphology, Fourier transform infrared spectroscopy, ROS production test, cell uptake test and combined therapy treatment effect in vitro were evaluated to prove NIR triggered ROS-sensitive (UCN/SiO2-RB + DOX)@PPADT NPs. Based on our data, this delivery system could provide an effective means to realize simultaneous chemotherapy and PDT through external NIR-triggered ROS sensitivity.
Although the negative impacts of particulate matter (PM2.5) on human health have been well recognized, very few efforts have been paid to find new strategies to suppress the toxicity of PM2.5 both in vitro and in vivo. In this study, reactive oxygen species (ROS)-responsive nanoparticles made of poly(1,4-phenleneacetonedimethylene thioketal) (PPADT) were used to load immunosuppressant drug tacrolimus (FK506) with a drug loading efficiency of around 44%. The PPADT particles showed very good ROS-responsiveness and were degraded in an oxidation environment. By exhausting intracellular ROS, they could effectively suppress the toxicity of A549 lung epithelial cells and RAW264.7 macrophages induced by the PM2.5 particulates collected from three different regions in China. Moreover, the inflammatory response of PM2.5 could also be significantly suppressed, showing much better performance than the free FK506 drugs both in vitro and in vivo. This concept-proving research demonstrates the promising application for the ROS-sensitive drug release particles in dispelling the toxicity and suppressing the inflammation of PM2.5 pollutes, shedding a new light in the design and applications of stimuli-responsive systems in the bionanotechnology and healthcare fields.