Intracellular redox homeostasis and the iron metabolism system in tumor cells are closely associated with the limited efficacy of chemodynamic therapy (CDT). Despite extensive attempts, maintaining high levels of intracellular catalysts (free iron) and reactants (H2O2) while decreasing the content of reactive oxygen species (ROS) scavengers (especially glutathione (GSH)) for enduring CDT still remains great challenges. Herein, SS bond‐rich dendritic mesoporous organic silica nanoparticles (DMON) are utilized as GSH‐depleting agents. After co‐loading Fe0 and a catalase inhibitor (3‐amino‐1,2,4‐triazole (AT)), a novel biodegradable nanocarrier is constructed as DMON@Fe0/AT. In the mildly acidic tumor microenvironment, on‐demand ferrous ions and AT are intelligently released. AT suppresses the activity of catalase for H2O2 hoarding, and the exposed DMON weakens ROS scavenging systems by persistently depleting intracellular GSH. The highly efficient •OH production by DMON@Fe0/AT can effectively attack mitochondria and downregulate the expression of ferroportin 1, which can disrupt the cellular iron metabolism system, leading to the desired retention of iron in the cytoplasm. More importantly, DMON@Fe0/AT exhibits a much more efficient CDT killing effect on 4T1 tumor cells than plain Fe0 nanoparticles, benefiting from their synergistic redox regulation and iron metabolism disruption. Overall, the as‐prepared intelligent, degradable DMON@Fe0/AT provides an innovative strategy for enduring CDT.
Ions are essential to body, but sometimes can evolve into weapons to attack and destroy cells without systematic toxicity and drug resistance. Inspired by nitric oxygen as neurotransmitter in mediating Ca2+ release, NO nanodonors with high photoreactivity and stability are constructed with upconversion nanoparticles (UCNPs) coated by zeolitic nitro‐/nitrile‐imidazole framework‐82 (ZIF‐82), capable of near‐infrared light (NIR) triggered NO generation and berbamine (BER) release, to achieve cancer therapy with the stored Ca2+ in cells. The spatial confinement effect of 2‐nitroimidazole in ZIF‐82 enables NO‐releasing with tunable release kinetics. NO turns on the ryanodine receptors overexpressed in cancer cells for abrupt Ca2+ elevation; meanwhile, berbamine (BER) turns Ca2+‐excretion pumps off to inhibit calcium efflux, resulting in intracellular Ca2+ overload induced apoptosis. This work provides the first example of regulating endogenous ions for cell killing, which holds promise as an effective cancer therapeutics that is complementary to traditional chemotherapeutics.
Free radicals with reactive chemical properties can fight tumors without causing drug resistance. Reactive oxygen species (ROS) has been widely used for cancer treatment, but regrettably, the common O2 and H2O2 deficiency in tumors sets a severe barrier for sufficient ROS production, leading to unsatisfactory anticancer outcomes. Here, we construct a chlorine radical (.Cl) nano‐generator with SiO2‐coated upconversion nanoparticles (UCNPs) on the inside and Ag0/AgCl hetero‐dots on the outside. Upon near‐infrared (NIR) light irradiation, the short‐wavelength emission UCNP catalyzes .Cl generation from Ag0/AgCl with no dependence on O2/H2O2. .Cl with strong oxidizing capacity and nucleophilicity can attack biomolecules in cancer cells more effectively than ROS. This .Cl stress treatment will no doubt broaden the family of oxidative stress‐induced antitumor strategies by using non‐oxygen free radicals, which is significant in the development of new anticancer agents.
Timely detection of liver fibrosis by X‐ray computed tomography (CT) can prevent its progression to fatal liver diseases. However, it remains quite challenging because conventional CT can only identify the difference in density instead of X‐ray attenuation characteristics. Spectral CT can generate monochromatic imaging to specify X‐ray attenuation characteristics of the scanned matter. Herein, an X‐ray energy‐dependent attenuation strategy originated from bismuth (Bi)‐based nanoprobes (BiF3@PDA@HA) is proposed for the accurate diagnosis of liver fibrosis. Bi element in BiF3@PDA@HA can exhibit characteristic attenuation depending on different levels of X‐ray energy via spectral CT, and that is challenging for conventional CT. In this study, selectively accumulating BiF3@PDA@HA nanoprobes in the hepatic fibrosis areas can significantly elevate CT value for 40 Hounsfield units on 70 keV monochromatic images, successfully differentiating from healthy livers and achieving the diagnosis of liver fibrosis. Furthermore, the enhancement produced by the BiF3@PDA@HA nanoprobes in vivo increases as the monochromatic energy decreases from 70 to 40 keV, optimizing the conspicuity of the diseased areas. As a proof of concept, the strategically designed nanoprobes with energy‐dependent attenuation characteristics not only expand the scope of CT application, but also hold excellent potential for precise imaging‐based disease diagnosis.
Free radicals with reactive chemical properties can fight tumors without causing drug resistance. Reactive oxygen species (ROS) has been widely used for cancer treatment, but regrettably, the common O2 and H2O2 deficiency in tumors sets a severe barrier for sufficient ROS production, leading to unsatisfactory anticancer outcomes. Here, we construct a chlorine radical (.Cl) nano‐generator with SiO2‐coated upconversion nanoparticles (UCNPs) on the inside and Ag0/AgCl hetero‐dots on the outside. Upon near‐infrared (NIR) light irradiation, the short‐wavelength emission UCNP catalyzes .Cl generation from Ag0/AgCl with no dependence on O2/H2O2. .Cl with strong oxidizing capacity and nucleophilicity can attack biomolecules in cancer cells more effectively than ROS. This .Cl stress treatment will no doubt broaden the family of oxidative stress‐induced antitumor strategies by using non‐oxygen free radicals, which is significant in the development of new anticancer agents.
Diagnosis of Liver fibrosisBismuth (Bi)-based nanomaterials can exhibit characteristic attenuation depending on different levels of X-ray energy, known as "energy-dependent attenuation". Liver-fibrosis-targeted Bi-based nanomaterials, BiF3@PDA@HA, can exhibit characteristic attenuation on monoenergetic X-ray, endowing the diagnosis of liver fibrosis via monoenergetic imaging of spectral computed tomography. More details can be found in article number 2002548 by Yan Zhou, Wenbo Bu, Zhenwei Yao and co-workers.
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