Multifunctional AuPt Nanoparticles for Synergistic Photothermal and Radiation Therapy.

Background: Photothermal therapy (PTT) has gained considerable interest as an emerging modality for cancer treatment in recent years. Radiation therapy (RT) has been widely used in the clinic as a traditional treatment method. However, RT and PTT treatments are limited by side effects and penetration depth, respectively. In addition, hypoxia within the tumor can lead to increased resistance to treatment. Methods: We synthesized multiple sizes of AuPt by modulating the reaction conditions. The smallest size of AuPt was selected and modified with folic acid (FA) for PTT and RT synergy therapy. Various methods including transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FITR) are used to determine the structure and composition of AuPt-FA (AF). In addition, we researched the photothermal properties of AF with IR cameras and infrared lasers. Flow cytometry, colony formation assays, CCK8, and fluorescent staining for probing the treatment effect in vitro. Also, we explored the targeting of AF by TEM and In Vivo Imaging Systems (IVIS). In vivo experiments, we record changes in tumor volume and weight as well as staining of tumor sections (ROS, Ki67, and hematoxylin and eosin). Results: The AuPt with particle size of 16 nm endows it with remarkably high photothermal conversion efficiency (46.84%) and catalase activity compared to other sizes of AuPt (30 nm and 100 nm). AF alleviates hypoxia in the tumor microenvironment, leading to the production of more reactive oxygen species (ROS) during the treatment. In addition, the therapeutic effect was significantly enhanced by combining RT and PTT, with an apoptosis rate of 81.1% in vitro and an in vivo tumor volume reduction rate of 94.0% in vivo. Conclusion: These results demonstrate that AF potentiates the synergistic effect of PTT and RT and has the potential for clinical translation.

An intratumoral injectable nanozyme hydrogel for hypoxia-resistant thermoradiotherapy.

Hypoxia in local tumors leads to the failure or resistance of radiotherapy (RT) and high-dose RT will cause systemic reactions and local radiation damage. As a non-chemotherapeutic intervention, photothermal therapy (PTT) can remove tumor tissues through thermal ablation as well as effectively improve the microenvironment of hypoxic cells. Therefore, the combined use of PTT and RT (thermoradiotherapy) has urgently become an efficient treatment. In this work, by encapsulating prussian blue (PB) nanoparticles in agarose hydrogel, we developed an injectable hybrid light-controlled hydrogel system as a PB reservoir and release controller (PRC) which can realize single injection and multiple treatments in vivo. Under the irradiation of 808 nm near-infrared (NIR) laser, PB nanoparticles convert laser energy into heat energy, causing degradation of agarose hydrogel and the release of PB nanoparticles. Due to the excellent photothermal properties of PB, photothermal treatment in the NIR Biological Windows can greatly enhance the sensitivity of tumor cells to RT. Meanwhile, PB nanoparticles can also be a nanozyme to drive the decomposition of endogenous hydrogen peroxide (H2O2), and then generate oxygen (O2) to improve the tumor hypoxic microenvironment, achieving the further enhancement of the radiation sensitivity. Notably, this study is the first design to utilize hydrogel for thermoradiotherapy. Both in vitro and in vivo experiments, the PRC demonstrated excellent effects of PTT-RT, good stability and biocompatibility, indicating our nanoplatform promote the development of anti-cancer combination thermoradiotherapy with greater clinical significance.

Salt-Dependent RNA Pseudoknot Stability: Effect of Spatial Confinement.

Macromolecules, such as RNAs, reside in crowded cell environments, which could strongly affect the folded structures and stability of RNAs. The emergence of RNA-driven phase separation in biology further stresses the potential functional roles of molecular crowding. In this work, we employed the coarse-grained model that was previously developed by us to predict 3D structures and stability of the mouse mammary tumor virus (MMTV) pseudoknot under different spatial confinements over a wide range of salt concentrations. The results show that spatial confinements can not only enhance the compactness and stability of MMTV pseudoknot structures but also weaken the dependence of the RNA structure compactness and stability on salt concentration. Based on our microscopic analyses, we found that the effect of spatial confinement on the salt-dependent RNA pseudoknot stability mainly comes through the spatial suppression of extended conformations, which are prevalent in the partially/fully unfolded states, especially at low ion concentrations. Furthermore, our comprehensive analyses revealed that the thermally unfolding pathway of the pseudoknot can be significantly modulated by spatial confinements, since the intermediate states with more extended conformations would loss favor when spatial confinements are introduced.