Besides the conventional carbon sources, acetyl-CoA has recently been shown to be generated from acetate in various types of cancers, where it promotes lipid synthesis and tumour growth. The underlying mechanism, however, remains largely unknown. We find that acetate induces a hyperacetylated state of histone H3 in hypoxic cells. Acetate predominately activates lipogenic genes ACACA and FASN expression by increasing H3K9, H3K27 and H3K56 acetylation levels at their promoter regions, thus enhancing de novo lipid synthesis, which combines with its function as the metabolic precursor for fatty acid synthesis. Acetyl-CoA synthetases (ACSS1, ACSS2) are involved in this acetate-mediated epigenetic regulation. More importantly, human hepatocellular carcinoma with high ACSS1/2 expression exhibit increased histone H3 acetylation and FASN expression. Taken together, this study demonstrates that acetate, in addition to its ability to induce fatty acid synthesis as an immediate metabolic precursor, also functions as an epigenetic metabolite to promote cancer cell survival under hypoxic stress.

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.

Highly sensitive and specific discrimination of brain tumor margins from the surrounding parenchyma remains a formidable challenge. Limited by the short of photostable probes with deep tissue penetration and high efficiency of crossing the blood-brain-barrier (BBB), the development of fluorescence-guided surgery (FGS) of brain tumors was markedly constrained. Herein, we report the capability of the strong second near-infrared-IIb (NIR IIb, 1500−1700 nm) fluorescence from Er-based lanthanide nanoparticles in imaging-guided surgery of orthotopic glioma. We designed an energy-cascaded Er 3+ -Ce 3+ -A 3+ (A = Yb, Ho, Tm) system and prepared a series of NaErF 4 :Ce@NaAF 4 @NaLuF 4 down-conversion nanoparticles (DCNPs) for optimizing the influence of NaAF 4 interlayer and Ce 3+ dopants. We modified the optimal NaErF 4 :2.5 %Ce@NaYbF 4 (0.9 nm)@NaLuF 4 DCNPs with Dye-brush polymer (Dye-BP) to facilitate 4 I 13/2 → 4 I 15/2 transition, which leads to an impressive 675-fold enhancement of 1525 nm fluorescence in aqueous solution under 808 nm excitation due to the excellent energy-cascaded downconversion (ECD), in comparison with that of NaErF 4 nanoparticles. We further modified these highly bright nanoparticles with tumor-targeting angiopep-2 peptide, and efficiently delivered them to the glioma by using the focused ultrasound sonication (FUS) to temporarily open the BBB. We obtained the highest tumorto-background ratio (TBR = 12.5) ever reported in the targeted NIR IIb fluorescence imaging of small orthotopic glioma (size < 3 mm, depth> 3 mm) through intact skull and scalp, which was drastically improved to ∼150 after cardiac perfusion and craniotomy to ensure the precise resection of tumor. More importantly, the size of glioma measured from the width of fluorescence profile is very close to that from T 2 -weighted MRI images. Our work provides the insights into engineering NIR IIb fluorescence of lanthanide nanoparticles, and demonstrates the great potential of NIR IIb fluorescence imaging-guided surgery of tumor.

Nanoscale ternary chalcogenides have attracted intense research interest due to their wealth of tunable properties and diverse applications in energy and environmental and biomedical fields. In this article, ultrasmall magnetic CuFeSe ternary nanocrystals (<5.0 nm) were fabricated in the presence of thiol-functionalized poly(methacrylic acid) by an environmentally friendly aqueous method under ambient conditions. The small band gap and the existence of intermediate bands lead to a broad NIR absorbance in the range of 500-1100 nm and high photothermal conversion efficiency (82%) of CuFeSe nanocrystals. The resultant CuFeSe nanocrystals show superparamagnetism and effective attenuation for X-rays. In addition, they also exhibit excellent water solubility, colloidal stability, biocompatibility, and multifunctional groups. These properties enable them to be an ideal nanotheranostic agent for multimodal imaging [e.g., photoacoustic imaging (PAI), magnetic resonance imaging (MRI), computed tomography (CT) imaging] guided photothermal therapy of cancer.

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.