Immune profiling before treatment is predictive of TLR9-induced antitumor efficacy.

TLR9 targeting has been a dynamic research field with promising potential in tumor immunotherapy. However, why most patients do not respond to TLR9 agonists remains unknown. In our attempt to resolve this issue, we observed that anti-tumor response to our TLR9-targeting cancer nanomedicines varied according to the initial immune profile of the animals. Speculating that immune profiling before treatment, including the measurement of IFN-α, IL-12, IL-6, TNF, tumor-infiltrating lymphocytes and spleen-residing lymphocytes, could be used to predictively distinguish responders from non-responders, we performed experiments in two different tumor models 4T1-BALB/c and B16-C57BL/6, to validate the hypothesis. Results confirmed that antitumor efficacy with respect to tumor growth, immune cell infiltration, and cytokines release, correlated with the different condition of individuals, as well as the categorization of the animals. This work suggests that immune profiling before treatment might be able to predict the antitumor efficacy of TLR9 agonists in vivo.

Iron (II) Polypyridyl Complexes as Antiglioblastoma Agents to Overcome the Blood-Brain Barrier and Inhibit Cell Proliferation by Regulating p53 and 4E-BP1 Pathways.

Background and Purpose: It is urgently required to develop promising candidates to permeate across blood-brain barrier (BBB) efficiently with simultaneous disrupting vasculogenic mimicry capability of gliomas. Previously, a series of iron (II) complexes were synthesized through a modified method. Hence, the aim of this study was to evaluate anticancer activity of Fe(PIP)3SO4 against glioma cancer cells. Methods: Cytotoxic effects were determined via MTT assay, and IC50 values were utilized to evaluate the cytotoxicity. Cellular uptake of Fe(PIP)3SO4 between U87 and HEB cells was conducted by subtracting content of the complex remaining in the cell culture supernatants. Propidium Iodide (PI)-flow cytometric analysis was used to analyze cell cycle proportion of U87 cells treated with Fe(PIP)3SO4. The reactive oxygen species levels induced by Fe(PIP)3SO4 were measured by 2'-deoxycoformycin (DCF) probe; ABTS assay was utilized to examine the radical scavenge capacity of Fe(PIP)3SO4. To study the bind efficiency to thioredoxin reductase (TrxR), Fe(PIP)3SO4 was introduced into solution containing TrxR. To verify if Fe(PIP)3SO4 could penetrate BBB, HBMEC/U87 coculture as BBB model was established, and penetrating capability of Fe(PIP)3SO4 was tested. In vitro U87 tumor spheroids were formed to test the permeating ability of Fe(PIP)3SO4. Acute toxicity and biodistribution of Fe(PIP)3SO4 were tested on mice for 72 h. Protein profiles associated with U87 cells treated with Fe(PIP)3SO4 were determined by Western blotting analysis. Results: Results showed that Fe(PIP)3SO4 could suppress cell proliferation by inducing G2/M phase cycle retardation and apoptotic pathways, which was related with expression of p53 and initiation factor 4E binding protein 1. In addition, Fe complex could suppress cell proliferation by downregulating reactive oxygen species levels via scavenging free radicals and interaction with TrxR. Furthermore, Fe(PIP)3SO4 could permeate across BBB and simultaneously inhibited the vasculogenic mimicry-channel of U87 cells, suggesting favorable antiglioblastoma efficacy. Acute toxicity manifested lower degree of the complex compared with cisplatin and temozolomide. Conclusion: Fe(PIP)3SO4 exhibited favorable anticancer activity against glioma cells associated with p53 and 4E binding protein 1, accompanied with negligible toxic effects on normal tissues. Herein, Fe(PIP)3SO4 could be developed as a promising metal-based chemotherapeutic agent to overcome BBB and antagonize glioblastomas.

Facile Nanolization Strategy for Therapeutic Ganoderma Lucidum Spore Oil to Achieve Enhanced Protection against Radiation-Induced Heart Disease.

Radiotherapy (RT) has been extensively utilized for clinical cancer therapy, however, excessive generation of reactive oxygen species (ROS) is becoming a main cause for radiation-induced heart disease (RIHD). Ganoderma lucidum spore oil (GLSO) is a popular functional food composite with potent antioxidant activity, but it is compromised by poor solubility and stability for further application. Therefore, a strategy for rational fabrication of GLSO@P188/PEG400 nanosystem (NS) is demonstrated in this study to realize good water solubility and achieve enhanced protection against RIHD. As expected, GLSO@P188/PEG400 NS can attenuate X-ray-induced excessive ROS levels thanks to its enhanced free radical scavenging capability, simultaneously protecting on mitochondria from X-ray irradiation (IR). Moreover, GLSO@P188/PEG400 NS alleviates DNA damage and promotes self-repair processes against IR, thus recovering G0/G1 proportion back to normal levels. Furthermore, pre- and post-treated GLSO@P188/PEG400 NS demonstrates potential protection on heart from X-rays in vivo, as evidenced by attenuating cardiac dysfunction and myocardial fibrosis. Meanwhile, the cell antioxidant capacity (including T-SOD, MDA, and GSH-x) stays in balance during this process. This study not only provides a promising strategy for facile nanolization of functional food composites with hydrophobic defects but also sheds light on their cardiac protection and action mechanisms against IR-induced disease.

Tea regimen, a comprehensive assessment of antioxidant and antitumor activities of tea extract produced by Tie Guanyin hybridization.

A comprehensive assessment was conducted in this study to examine the antioxidant and antitumor activities of tea extract produced by Tie Guanyin hybridization. Two radical-scavenging systems of assay in vitro, namely ABTS and DPPH assays, were used to investigate the antioxidant activity of the summer tea and autumn tea extract (STE and ATE) derived from the Jin Guanyin. The results indicated that the major active ingredients were catechins, and the theaflavin is rare in the STE and ATE. Moreover, STE and ATE could significantly suppress the growth of human breast cancer cells MDA-MB-231 in a dose-dependent manner, and wrecked the morphology of mitochondria, activated caspase families, leading to the cancer cell death by both apoptosis and cell cycle arrest pathways. Based on the results from an MDA-MB-231 xenograft nude mice model, STE could effectively prevent the tumor formation, and greatly improve the mice immunity and thus improve their living conditions. Taken together, ATE and STE could act as a healthy and prospective substitute for natural antioxidants and a promising prophylactic agent against cancer. This finding provides a great promising nutritional approach to treat diseases related with oxidative stress.