A Universally EDTA-Assisted Synthesis of Polytypic Bismuth Telluride Nanoplates with a Size-Dependent Enhancement of Tumor Radiosensitivity and Metabolism In Vivo.

Bismuth telluride (Bi2Te3) is an available thermoelectric material with the lowest band gap among bismuth chalcogenides, revealing a broad application in photocatalysis. Unfortunately, its size and morphology related to a radio-catalysis property have rarely been explored. Herein, an ethylenediaminetetraacetic acid (EDTA)-assisted hydrothermal strategy was introduced to synthesize polytypic Bi2Te3 nanoplates (BT NPs) that exhibit size-dependent radio-sensitization and metabolism characteristics in vivo. By simply varying the molar ratio of EDTA/Bi3+ during the reaction, BT NPs with different sizes and morphologies were obtained. EDTA acting as chelating agent and "capping" agent contributed to the homogeneous growth of BT NPs by eliminating dangling bonds and reducing the surface energy of different facets. Further analyzing the size-dependent radio-sensitization mechanism, larger-sized BT NPs generated holes that preferentially catalyzed the conversion of OH- to ·OH when irradiated with X-rays, while the smaller-sized BT NPs exhibited faster decay kinetics producing higher 1O2 levels to enhance radiotherapy effects. A metabolomic analysis revealed that larger-sized BT NPs were oxidized into Bi(Ox) in the liver via a citrate cycle pathway, whereas smaller-sized BT NPs accumulated in the kidney and were excreted in urine in the form of ions by regulating the metabolism of glutamate. In a cervical cancer model, BT NPs combined with X-ray irradiation significantly antagonized tumor suppression through the promotion of apoptosis in tumor cells. Consequently, in addition to providing a prospect of BT NPs as an efficient radio-sensitizer to boost the tumor radiosensitivity, we put forth a strategy that can be universally applied in synthesizing metal chalcogenides for catalysis-promoted radiotherapy.

Translational Nanotherapeutics Reprograms Immune Microenvironment in Malignant Pleural Effusion of Lung Adenocarcinoma.

Malignant pleural effusion (MPE) remains a treatment bottleneck in advanced lung cancer, due to its complicated microenvironments and "cold" immunity. Therefore, the search for therapeutic drugs to transform MPE to functionally "hot" one could advance the development of effective immunotherapeutic strategy. Herein, translational selenium nanoparticles coated with immune-modulating macromolecule lentinan (SeNPs@LNT) are designed to restore the dysfunctional immune cells in patient-derived MPE microenvironment. Internalization of the SeNPs@LNT can effectively reduce the immunosuppressive status by enhancing the proliferation of CD4+ T cells and natural killer cells, and remodeling the tumor associated macrophages into tumoricidal M1 phenotype in MPE derived from patients presenting low Se levels in blood and pleural effusion. Th1, cytotoxic T cell, γδ T, and B cell functions are upregulated, and Th2, Th17, and Treg cells activity is downregulated. Furthermore, SeNPs@LNT can be gradually metabolized into SeCys2 to promote the production of metabolites associated with tumor growth inhibition and immune response activation in MPE microenvironment. In contrast, lung cancer markers and vitamin B6 metabolism are decreased. The translational SeNP-based nanotherapeutic strategy restores functional "cold" MPE to "hot" MPE to activate the immune responses of various immune cells in MPE of lung cancer patients.

Phoenix Dan Cong Tea: An Oolong Tea variety with promising antioxidant and in vitro anticancer activity.

BACKGROUND: Phoenix Dan Cong tea is an Oolong tea produced in Chaozhou, China. Nowaday, the experimental studies on the benefical effects of the Phoenix Dan Cong tea are rare. OBJECTIVE: The objective of this study was to comprehensively evaluate the activity of Phoenix Dan Cong tea aqueous extract (PDCe). METHODS: We used a series of evaluation methods in the present study to achieve an in-depth understanding and evaluation of the antioxidant and antitumor activity of PDCe. RESULTS: High-performance liquid chromatography (HPLC) studies have indicated that PDCe is rich in catechins such as gallocatechin (GC), epigallocatechin (EGCG) and epicatechin gallate (ECG), with sparse amounts of theaflavins. We discovered that PDCe scavenges ABTS•+ and DPPH• free radicals in a dose-dependent manner. In addition, PDCe can significantly induce apoptosis of MDA-MB231 cells, mainly through the death-receptor-mediated extrinsic apoptotic pathway. Internalized PDCe can not only downregulate intracellular reactive oxygen species levels but also induce oxidative damage to mitochondria in MDA-MB231 cells. CONCLUSIONS: Phoenix Dan Cong tea may act as a substitute for natural antioxidants and as a promising anticancer agent due to its protective effect on human health.

Overcoming blood-brain barrier by HER2-targeted nanosystem to suppress glioblastoma cell migration, invasion and tumor growth.

Efficient therapy of glioblastoma remains a big clinical challenge due to the existence of a blood-brain barrier (BBB) that prevents the delivery of anti-cancer drugs to the brain. In this study, a HER2 antibody-conjugated selenium nanoparticle platform was rationally designed and synthesised and was found to be capable of overcoming the BBB efficiently and delivering anti-cancer cargoes precisely to brain tissues. The BBB-overcoming efficacy of the nanosystem (HER2@NPs) was evaluated using in vitro cell co-culture model and in vivo mouse model. The results demonstrated that HER2 functionalization effectively enhanced BBB permeability of the NPs, which could significantly inhibit the growth of U251 glioblastoma tumor spheroids. Examination of the action mechanisms revealed that HER2@NPs entered the cancer cells through receptor-mediated endocytosis and then triggered DNA damage-mediated p53 signalling pathways. Moreover, by using superparamagnetic iron oxide nanoparticles (SPIONs) as a probe in a clinically used magnetic resonance imaging (MRI) system, we found that HER2@NPs effectively deliver SPIONs into the brain. Taken together, this study provides a cancer-targeting nanosystem for the delivery of anti-cancer drugs and MRI contrast agents overcoming the BBB to enable a precise future theranosis of malignant glioma in humans.

Designing Core-Shell Gold and Selenium Nanocomposites for Cancer Radiochemotherapy.

Radiotherapy is an important regime for treating malignant tumors. There is interest in the development of radiosensitizers to increase the local treatment efficacy under a relatively low and safe radiation dose. In this study, we designed Au@Se-R/A nanocomposites (Au@Se-R/A NCs) as nano-radiosensitizer to realize synergistic radiochemotherapy based on the radiotherapy sensitization property of Au nanorods (NRs) and antitumor activity of Se NPs. In vitro studies show that the combined treatment of A375 melanoma cells in culture with NCs and X-ray induces cell apoptosis through alteration in expression of p53 and DNA-damaging genes and triggers intracellular ROS overproduction, leading to greatly enhanced anticancer efficacy. Further studies using clinically used radiotherapy equipment demonstrate that the combined treatment of NCs and X-ray significantly inhibits the tumor growth in vivo and shows negligible acute toxicity to the major organs. Taken together, this study provides a strategy for clinical translation application of nanomedicne in cancer radiochemotherapy.

Phycocyanin-based nanocarrier as a new nanoplatform for efficient overcoming of cancer drug resistance.

Resistance to chemotherapy remains the primary obstacle for the successful treatment of cancers. Nanotechnology-based studies have developed many smart nanomedicines and efficient strategies to overcome multidrug resistance (MDR), which have brought new horizons to cancer therapy. Among them, protein-based nanomedicine represents an appealing drug delivery platform to realize safe and superior therapeutic effects due to its paramount biocompatibility with minimized toxicity. Herein we describe the rational design and construction of a novel protein-based nanocarrier using the naturally-occurring protein phycocyanin (PC) as the base material, to achieve safe and tumor-specific drug delivery. This cancer-targeting nanosystem (FA-PCNP@DOX) with bio-responsive properties exhibits positive targeting accumulation in resistant cancer cells and overcomes drug efflux by enhancing cellular uptake and retention time. Specifically, FA-PCNP@DOX inhibits the function of pumping proteins of the ABC family and triggers ROS-mediated apoptotic signaling pathways, thereby attaining highly efficient anticancer efficacy and overcoming drug resistance. Pharmaceutical studies demonstrate that FA-PCNP@DOX overwhelms DOX by sustained release in the blood, which verifies its prolonged circulation in vivo. Moreover, FA-PCNP@DOX efficiently accumulates in tumors and strengthens the tumor inhibitory effect of DOX by enhanced tumoral penetration. Importantly, FA-PCNP@DOX effectively reduces the hepatic, pulmonary, renal and cardiac toxicity caused by DOX. Therefore, as a new nanocarrier, this novel nanosystem could be further exploited as a safe and versatile nanoplatform for next-generation cancer therapy.