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Hypoxemia after acute myocardial infarction (AMI) causes severe damage to cardiac cells and induces cardiac dysfunction. Protection of cardiac cells and reconstruction of cardiac functions by re-introducing oxygen into the infarcted myocardium represents an efficient approach for the treatment of AMI. However, the established methods for oxygen supplementation mainly focus on systemic oxygen delivery, which always results in inevitable oxidative stress on normal tissues. In this work, an ultrasound (US) activated oxygen generation nanosystem has been developed, which specifically releases oxygen in the infarcted myocardium and alleviates the hypoxemic myocardial microenvironment to protect cardiac cells after AMI. The nanosystem was constructed through the formation of calcium peroxide in the mesopores of biocompatible mesoporous silica nanoplatforms, followed by the assembly of the thermosensitive material heneicosane and polyethyleneglycol. The mild hyperthermia induced by US irradiation triggered the phase change of heneicosane, thus achieving US responsive diffusion of water and release of oxygen. The US-activated oxygen release significantly alleviated the hypoxia and facilitated the mitigation of oxidative stress after AMI. Consequently, the survival of cardiac cells under hypoxic conditions was substantially improved and the damage in the infarcted myocardial tissue was minimized. This US-activated oxygen generation nanosystem may provide an efficient modality for the treatment of AMI.

Tumor hypoxia is a negative prognostic factor in cancer radiotherapy, due in part to its role in causing resistance to radiotherapy. It has attracted extensive critical attention to radiation sensitizers by using active oxygen to improve radiotherapy outcome. Active oxygen delivery functional materials are promising candidates to transport active oxygen to tumor cells. Herein, we report an oxygen delivery functional material by using hollow mesoporous silica nanoparticles (HMSNs) as carriers, synthesizing sodium percarbonate (SPC) in the channels and cavity of HMSNs (SPC@HMSNs) and coating polyacrylic acid (PAA) on the functional materials (SPC@HMSNs–PAA). SPC@HMSNs–PAA could release more SPC in a simulated tumor acidic microenvironment (pH ∼ 6.5), which can provide oxygen to improve radiotherapy outcome even under low energy X-ray irradiation. The events induce obvious overproduction of reactive oxygen radicals to kill cancer cells with a significant effect. Meanwhile, no obvious cytotoxicity was observed when SPC@HMSNs–PAA applied alone. The radiosensitization of SPC@HMSNs–PAA on cancer cells, even exposure to low-energy X-ray irradiation, may suggest promising application in radiotherapy.

Discography often destroys the hypoxic environment in the intervertebral disc and accelerates intervertebral disc degeneration (IVDD). Therefore, it often fails to meet the requirements for application in clinical practice. This technology mainly increases the reactive oxygen species (ROS) in the IVD. As so, it is particularly critical to develop strategies to avoid this degeneration mechanism. Prussian blue nanoparticles (PBNPs) are found to enhance development under magnetic resonance T1 and have antioxidant enzyme activity. The key results of the present study confirm that PBNPs alleviate intracellular oxidative stress and increase the intracellular activities of antioxidant enzymes, such as superoxide dismutase 1 (SOD1). PBNPs can rescue nucleus pulposus cell degeneration by increasing oxidoreductase system-related mRNA and proteins, especially by stabilizing SOD1 from ubiquitination-proteasome degradation, thus improving the mitochondrial structure to increase antioxidation ability, and finally rescuing ROS-induced IVDD in a rat model. Therefore, it is considered that PBNPs can be a potential antioxidation-protective discography contrast agent.

Conventional chemotherapy uses potent toxic drugs to destroy cancer cells and always causes severe systemic toxicity in patients. In this respect, a smart and pH-switched prodrug/procatalyst co-delivery nanosystem is developed which is non-toxic toward normal cells and is inert during its delivery in the vasculature, while responsively functions in acidic lysosomes inside cancer cells. Synthetically, non-toxic artemisinin (ART) was used as the prodrug and loaded into the inner space of hollow mesoporous silica (HMS) nanoparticles (NPs). Subsequently, Fe3O4 NPs were efficiently capped onto pore outlets of HMS via acid labile acetal linkers (ART@HMS-Fe3O4). ART@HMS-Fe3O4 was stable under neutral conditions (pH 7.4) with almost no leakage of ART. Upon exposure to the acidic lysosomal compartment (pH 3.8–5.0) in cells, the acetal linkers were hydrolyzed which led to sustained release of both ART and Fe3O4 NPs. Under the activation of the lysosomal environment, the liberated Fe3O4 NPs were metabolized to free iron ions and catalyzed the generation of high amounts of free radicals from the released ART in cells. In vitro cytotoxicity assay revealed excellent anticancer efficacy of this ART/Fe3O4 co-delivery nanosystem. The Fe3O4 NPs acted both as gatekeepers and procatalysts which inhibited ART from leakage during their delivery, while released ART and activated chain reactions to form free radicals in acidic lysosomes inside cancer cells. We visualize that this lysosomal environment-responsive ART@HMS-Fe3O4 nanosystem could serve as an efficient and desirable chemotherapeutic nanosystem for cancer therapy.

Excess reactive oxygen species (ROS) have been proved to damage cancer cells efficiently. ROS overproduction is thus greatly desirable for cancer therapy. To date, ROS production is generally uncontrollable and outside cells, which always bring severe side-effects in the vasculature. Since most ROS share a very short half-life and primarily react close to their site of formation, it would be more efficient if excess ROS are controllably produced inside cancer cells. Herein, we report an efficient lysosome-controlled ROS overproduction via a pH-responsive catalytic nanosystem (FeOx-MSNs), which catalyze the decomposition of H2O2 to produce considerable ROS selectively inside the acidic lysosomes (pH 5.0) of cancer cells. After a further incorporation of ROS-sensitive TMB into the nanosystem (FeOx-MSNs-TMB), both a distinct cell labeling and an efficient death of breast carcinoma cells are obtained. This lysosome-controlled efficient ROS overproduction suggests promising applications in cancer treatments.

Excessive free radicals are noxious for living organisms and lead to cell death. Destruction of malignant cells by reactive free radicals has been widely used in cancer treatment. A key consideration is how to allow targeted free radical attack on cancer cells and avoid unwanted side-effects. Herein, we develop an efficient intracellular free radical generation strategy against cancer cells by delivering active ingredients into cancer cells, where free radicals are selectively generated by a lysosomal bioactivation process. Artesunate (ART), which is non-toxic to normal cells, was chosen as the free radical source and transported into cells with a hollow mesoporous silica-based delivery system (ART@HMS). To selectively activate the ART@HMS inside cancer cells, a high-bioactive Fe/O cluster-mesoporous silica nanosystem (Fe/O-MSN) was elaborately prepared. Under the bioactivation of the lysosome, the low-dose ART@HMS together with biocompatible Fe/O-MSN induced significant intracellular generation of toxic free radicals and efficient death of cancer cells. This selective intracellular free radical generation strategy is encouraging for its development into an effective low-cost cancer therapy.

We herein report the optical diffuse reflection properties of hollow mesoporous silica nanospheres (HMSNs). The HMSNs reflect more than 90% of the UV and visible light in the wide range of 240–800 nm and more than 70% of the UV light shorter than 240 nm, which are significantly higher than that of the bulk silica. The high reflectance of the HMSNs mainly arises from multiple scattering, which is caused by the disordered arrangement of nanospheres with thickness up to several hundred nanometers. Besides, the unique microstructure of HMSNs and the comparable size of HMSNs with UV light may also contribute to their high reflection according to the Mie scattering principles. Unlike semiconductor materials which shield UV light by absorbing UV light and generating reactive species, the HMSNs display extremely low absorption in the UV light region. The high UV light reflection properties as well as the specific hollow mesoporous structures of the HMSNs indicate their superior applications in UV light shielding devices.

Free radicals are toxic entities known to cause cellular damage and to mediate cell death. We herein develop a controlled free radical generation strategy for cancer therapy via pH-responsive release of benzoyl peroxide (BPO) in tumor cells and producing free radicals to mediate cell death. BPO as the free radical resource was encapsulated into a chitosan (Cs)-coated mesoporous silica nanocomposite (BPO@HMSNs-Cs). The mesoporous silica carrier improved the BPO solubility by preventing its crystallization and promoted its stability by inclusion. Chitosan imparted the nanocomposite pH-responsive BPO release capacity with enhanced BPO release in simulated acidic tumor media (pH 6.5) and minor release in simulated normal tissue media (pH 7.4). The enhanced free radical generation in tumor media further led to significantly higher cytotoxicity in the tumor at acidic pH 6.5 than at physiological pH 7.4. The free radical-mediated cytotoxicity of BPO@HMSNs-Cs was verified by the observation of free radical-induced green fluorescence in cells. This pH-responsive free radical generation nanocomposite may provide new opportunities for controlled drug delivery and cancer therapy.