Fenton reaction–based chemodynamic therapy (CDT) has attracted considerable attention for tumor treatment, because the Fenton reaction can degrade endogenous H2O2 within the tumor to form reactive oxygen species (ROS) to kill cancer cells. The kinetics of the Fenton reaction has significantly influenced its treatment efficacy. It is crucial to enhance the reaction kinetics at the maximum H2O2 concentration to quickly produce vast amounts of ROS to achieve treatment efficacy, which to date, has not been realized. Herein, reported is an efficacious CDT treatment of breast cancer using biomimetic CS‐GOD@CM nanocatalysts, which are rationally designed to significantly boost the Fenton reaction through improvement of H2O2 concentration within tumors, and application of the second near‐infrared (NIR‐II) light irradiation at the maximum concentration, which is monitored by photoacoustic imaging. The biomimetic nanocatalysts are composed of ultra‐small Cu2−xSe (CS) nanoparticles, glucose oxidase (GOD), and tumor cell membrane (CM). The nanocatalysts can be retained in tumor for more than two days to oxidize glucose and produce an approximately 2.6‐fold increase in H2O2 to enhance the Fenton reaction under the NIR‐II irradiation. This work demonstrates for the first time the CDT treatment of cancer enhanced by the NIR‐II light.

The small difference between tumor and normal tissues in their responses to ionizing radiation has been a significant issue for radiotherapy of tumors. Herein, we report that dumbbell-shaped heterogeneous copper selenide-gold nanocrystals can serve as an efficient radiosensitizer for enhanced radiotherapy. The mean lethal dose of X-rays to 4T1 tumor cells can be drastically decreased about 40%, that is, decreasing from 1.81 to 1.10 Gy after culture with heterostructures. Due to the synergetic effect of heterostructures, the dose of X-rays is also much lower than those obtained from mixture of Cu2–x Se + Au nanoparticles (1.78 Gy), Cu2–x Se nanoparticles (1.72 Gy) and Au nanoparticles (1.50 Gy), respectively. We demonstrate that the sensitivity enhancement ratio of Cu2–x Se nanoparticles was significantly improved 45% (i.e., from 1.1 to 1.6) after the formation of heterostructures with gold. We also show that the heteronanocrystals exhibit an enhanced photothermal conversion efficiency, due to the synergetic interactions of localized surface plasmon resonance. These properties highly feature them as a multimodal imaging contrast agent (particularly for photoacoustic imaging, computed tomography imaging, and single photon emission computed tomography after labeled with radioisotopes) and as a radiosensitizer for imaging guided synergetic radiophotothermal treatment of cancer. The research provides insights for engineering low-Z nanomaterials with high-Z elements to form heteronanostructures with enhanced synergetic performance for tumor theranostics.

Microglia as an important type of innate immune cell in the brain have been considered as an effective therapeutic target for the treatment of central nervous degenerative diseases. Herein, we report cell membrane coated novel biomimetic Cu2–x Se-PVP-Qe nanoparticles (denoted as CSPQ@CM nanoparticles, where PVP is poly­(vinylpyrrolidone), Qe is quercetin, and CM is the cell membrane of neuron cells) for effectively targeting and modulating microglia to treat Parkinson’s disease (PD). The CSPQ nanoparticles exhibit multienzyme activities and could effectively scavenge the reactive oxygen species and promote the polarization of microglia into the anti-inflammatory M2-like phenotype to relieve neuroinflammation. We reveal that biomimetic CSPQ@CM nanoparticles targeted microglia through the specific interactions between the membrane surface vascular cells adhering to molecule-1 and α4β1 integrin expressed by microglia. They could significantly improve the symptoms of PD mice to result in an excellent therapeutic efficacy, as evidenced by the recovery of their dopamine level in cerebrospinal fluid, tyrosine hydroxylase, and ionized calcium binding adapter protein 1 to normal levels. Our work demonstrates the great potential of these robust biomimetic nanoparticles in the targeted treatment of PD and other central nervous degenerative diseases.

The reversible and controllable opening and recovery of the blood-brain barrier (BBB) is crucial for the treatment of brain diseases, and it is a big challenge to noninvasively monitor these processes. In this article, dual-modal photoacoustic imaging and single-photon-emission computed tomography imaging based on ultrasmall CuSe nanoparticles (3.0 nm) were used to noninvasively monitor the opening and recovery of the BBB induced by focused ultrasound in living mice. The ultrasmall CuSe nanoparticles were modified with poly(ethylene glycol) to exhibit a long blood circulation time. Both small size and long blood circulation time enable them to efficiently penetrate into the brain with the assistance of ultrasound, which resulted in a strong signal at the sonicated site and allowed for photoacoustic and single-photon emission computed tomography imaging monitoring the recovery of the opened BBB. The results of biodistribution, blood routine examination, and histological staining indicate that the accumulated CuSe nanoparticles could be excreted from the brain and other major organs after 15 days without causing side effects. By the combination of the advantages of noninvasive molecular imaging and focused ultrasound, the ultrasmall biocompatible CuSe nanoparticles holds great potential for the diagnosis and therapeutic treatment of brain diseases.

Breast cancer remains to show high mortality and poor prognosis in women despite of significant progress in recent diagnosis and treatment. Herein, we report the rational design of a highly efficient ultrasmall nanotheranostic agent with excellent photodynamic therapy (PDT) performance to against breast cancer and its metastasis by eliciting antitumor immunity. The ultrasmall nanoagent (3.1 ± 0.4 nm) was fabricated from polyethylene glycol modified Cu2–x Se nanoparticles, β-cyclodextrin, and chlorin e6 under ambient conditions. The resultant nanoplatform (CS–CD–Ce6 NPs) can be passively accumulated into the tumor to exhibit dramatic antitumor efficacy through the excellent PDT effect under near-infrared irradiation. The excellent PDT performance of this nanoplatform is owing to its role as a Fenton-like Haber–Weiss catalyst for the efficient degradation of H2O2 within the tumor to release hydroxyl radicals (·OH) and very toxic singlet oxygen (1O2) under irradiation. The generated vast amounts of reactive oxygen species not only killed primary tumor cells but also elicited immunogenic cell death (ICD) to release damage-associated molecular patterns (DAMPs) and induced proinflammatory M1-macrophages polarization. Thereby, antitumor immune responses against the metastasis of breast cancer were robustly evoked. Our work demonstrates that ultrasmall Cu2–x Se nanoparticle-based nanoplatform offers a promising way to prevent cancer metastasis via immunogenic effects through its excellent PDT performance.