Discovery of a Potent Glutathione Peroxidase 4 Inhibitor as a Selective Ferroptosis Inducer.

Potent and selective ferroptosis regulators promote an intensive understanding of the regulation and mechanisms underlying ferroptosis, which is highly associated with various diseases. In this study, through a stepwise structure optimization, a potent and selective ferroptosis inducer was developed targeting to inhibit glutathione peroxidase 4 (GPX4), and the structure-activity relationship (SAR) of these compounds was uncovered. Compound exhibited outstanding GPX4 inhibitory activity with a percent inhibition up to 71.

Engineered macrophages as near-infrared light activated drug vectors for chemo-photodynamic therapy of primary and bone metastatic breast cancer.

Patients with primary and bone metastatic breast cancer have significantly reduced survival and life quality. Due to the poor drug delivery efficiency of anti-metastasis therapy and the limited response rate of immunotherapy for breast cancer, effective treatment remains a formidable challenge. In this work, engineered macrophages (Oxa(IV)@ZnPc@M) carrying nanomedicine containing oxaliplatin prodrug and photosensitizer are designed as near-infrared (NIR) light-activated drug vectors, aiming to achieve enhanced chemo/photo/immunotherapy of primary and bone metastatic tumors.

Reduction-responsive dehydroepiandrosterone prodrug nanoparticles loaded with camptothecin for cancer therapy by enhancing oxidation therapy and cell replication inhibition.

The pentose phosphate pathway (PPP) plays a critical role by providing ribulose-5-phosphate (Ru5P) and NADPH for nucleotide synthesis and reduction energy, respectively. Accordingly, blocking the PPP process may be an effective strategy for enhancing oxidation therapy and inhibiting cell replication. Here, we designed a novel reduction-responsive PEGylated prodrug and constructed nanoparticles PsD@CPT to simultaneously deliver a PPP blocker, dehydroepiandrosterone (DHEA), and chemotherapeutic camptothecin (CPT) to integrate amplification of oxidation therapy and enhance cell replication inhibition.

Ischemia Modified Albumin and miR-126 Play Important Role in Diagnosis of Posterior Circulation Transient Ischemic Attack and Prediction of Secondary Cerebral Infarction.

Background: Transient ischemic attack (TIA) is a super warning for cerebral infarction stroke, thus probe of sensitive biomarker for TIA diagnosis and prognosis can contribute to make an optimal intervention plan.

Objective: This study was conducted to explore the value of ischemic modified albumin (IMA) and microRNA-12miR-126 on the diagnosis of posterior circulation TIA and the prediction of secondary cerebral infarction.

Study Design: This study was conducted as a longitudinal prospective research.

Bone-seeking nanoplatform co-delivering cisplatin and zoledronate for synergistic therapy of breast cancer bone metastasis and bone resorption.

The "vicious cycle" established between tumor growth and osteolysis aggravates the process of breast cancer bone metastasis, leading to life-threatening skeletal-related events that severely reduce survival and quality of life. To effectively interrupt the "vicious cycle", innovative therapeutic strategies that not only reduce osteolysis but also relieve tumor burden are urgently needed. Herein, a bone-seeking moiety, alendronate (ALN), functionalized coordination polymer nanoparticles (DZ@ALN) co-delivering cisplatin prodrug (DSP) and antiresorptive agent zoledronate (ZOL) Zn crosslinking for combination therapy was reported.

A light-triggered self-reinforced nanoagent for targeted chemo-photodynamic therapy of breast cancer bone metastases via ER stress and mitochondria mediated apoptotic pathways.

Current therapeutic strategies for the treatment of bone metastases are often limited by the lack of selectivity, severe systemic toxicity and suboptimal efficacy. Nanomedicine meditated chemo-photodynamic therapy provides a promising therapeutic opportunity for enhanced cancer therapy. Herein, we constructed an alendronate (ALN)-functionalized bone-seeking nanoagent (BTZ@ZnPc-ALN) to co-deliver the proteasome inhibitor bortezomib (BTZ) and the photosensitizer Zinc phthalocyanine (ZnPc) for synergistic chemo-photodynamic therapy of bone metastases.