Ultrasound-augmented enzyodynamic-Ca2+ overload synergetic tumor nanotherapy.

The excessive intracellular Ca2+ can induce oxidative stress, mitochondrial damage and cell apoptosis, which has been extensively explored for tumor therapy. However, the low Ca2+ accumulation originated from Ca2+-based nanosystems substantially weakens the therapeutic effect. Herein, a functional plant polyphenol-appended enzyodynamic nanozyme system CaFe2O4@BSA-curcumin (abbreviation as CFO-CUR) has been rationally designed and engineered to achieve magnified Ca2+ accumulation process, deleterious reactive oxygen species (ROS) production, as well as mitochondrial dysfunction through enzyodynamic-Ca2+ overload synergistic effect. The exogenous Ca2+ released by CaFe2O4 nanozymes under the weakly acidic tumor microenvironment and Ca2+ efflux inhibition by curcumin boost mitochondria-dominant antineoplastic efficiency. The presence of Fe components with multivalent characteristic depletes endogenous glutathione and outputs the incremental ROS due to the oxidase-, peroxidase-, glutathione peroxidase-mimicking activities. The ROS burst-triggered regulation of Ca2+ channels and pumps strengthens the intracellular Ca2+ accumulation. Especially, the exogenous ultrasound stimulation further amplifies mitochondrial damage. Both in vitro and in vivo experimental results affirm the ultrasound-augmented enzyodynamic-Ca2+ overload synergetic tumor inhibition outcomes. This study highlights the role of ultrasound coupled with functional nanozyme in the homeostasis imbalance and function disorder of mitochondria for highly efficient tumor treatment.

Silicon-containing nanomedicine and biomaterials: materials chemistry, multi-dimensional design, and biomedical application.

The invention of silica-based bioactive glass in the late 1960s has sparked significant interest in exploring a wide range of silicon-containing biomaterials from the macroscale to the nanoscale. Over the past few decades, these biomaterials have been extensively explored for their potential in diverse biomedical applications, considering their remarkable bioactivity, excellent biocompatibility, facile surface functionalization, controllable synthesis, etc. However, to expedite the clinical translation and the unexpected utilization of silicon-composed nanomedicine and biomaterials, it is highly desirable to achieve a thorough comprehension of their characteristics and biological effects from an overall perspective. In this review, we provide a comprehensive discussion on the state-of-the-art progress of silicon-composed biomaterials, including their classification, characteristics, fabrication methods, and versatile biomedical applications. Additionally, we highlight the multi-dimensional design of both pure and hybrid silicon-composed nanomedicine and biomaterials and their intrinsic biological effects and interactions with biological systems. Their extensive biomedical applications span from drug delivery and bioimaging to therapeutic interventions and regenerative medicine, showcasing the significance of their rational design and fabrication to meet specific requirements and optimize their theranostic performance. Additionally, we offer insights into the future prospects and potential challenges regarding silicon-composed nanomedicine and biomaterials. By shedding light on these exciting research advances, we aspire to foster further progress in the biomedical field and drive the development of innovative silicon-composed nanomedicine and biomaterials with transformative applications in biomedicine.

Reticular Chemistry-Enabled Sonodynamic Activity of Covalent Organic Frameworks for Nanodynamic Cancer Therapy.

The development of covalent organic framework (COF) sonosensitizers with intrinsic sonodynamic effects is highly desirable. However, such COFs are generally constructed using small-molecule photosensitizers. Herein, we report that the reticular chemistry-based synthesis of COFs from two inert monomers yields a COF-based sonosensitizer (TPE-NN) with inherent sonodynamic activity. Subsequently, a nanoscale COF TPE-NN is fabricated and embedded with copper (Cu)-coordinated sites to obtain TPE-NN-Cu. Results show that Cu coordination can enhance the sonodynamic effect of TPE-NN, whereas ultrasound (US) irradiation for sonodynamic therapy can augment the chemodynamic efficacy of TPE-NN-Cu. Consequently, TPE-NN-Cu upon US irradiation shows high-performance anticancer effects based on mutually reinforced sono-/chemo-nanodynamic therapy. This study reveals the backbone-originated sonodynamic activity of COFs and proposes a paradigm of intrinsic COF sonosensitizers for nanodynamic therapy.