A Novel Self-Assembled Mitochondria-Targeting Protein Nanoparticle Acting as Theranostic Platform for Cancer.

Self-assembled protein nanoparticles have attracted much attention in biomedicine because of their biocompatibility and biodegradability. Protein nanoparticles have become widely utilized as diagnostic or therapeutic agents for various cancers. However, there are no reports that protein nanoparticles can specifically target mitochondria. This targeting is desirable, since mitochondria are critical in the development of cancer cells. In this study, the discovery of a novel self-assembled metal protein nanoparticle, designated GST-MT-3, is reported, which targets the mitochondria of cancer cells within 30 min in vitro and rapidly accumulates in tumors within 1 h in vivo. The nanoparticles chelate cobalt ions [GST-MT-3(Co2+ )], which induces reactive oxygen species (ROS) production and reduces the mitochondrial membrane potential. These effects lead to antitumor activity in vivo. GST-MT-3(Co2+ ) with covalently conjugated paclitaxel synergistically suppress tumors and prolong survival. Importantly, the effective dosage of paclitaxel is 50-fold lower than that utilized in standard chemotherapy (0.2 vs 10 mg kg-1 ). To the best of the authors' knowledge, GST-MT-3 is the first reported protein nanoparticle that targets mitochondria. It has the potential to be an excellent platform for combination therapies.

Generation of a High-Affinity Nanobody Against CD147 for Tumor Targeting and Therapeutic Efficacy Through Conjugating Doxorubicin.

CD147, a glycosylated transmembrane protein in the immunoglobulin superfamily, is overexpressed on the surfaces of various tumor cells and promotes cancer cell proliferation, invasion, and metastasis. Nanobodies, characterized by small sizes, high affinities and specificities, and low immunogenicities, are promising diagnostic and therapeutic tools. However, there are few reports on nanobodies that specifically target CD147. In this work, a specific anti-CD147 nanobody has been successfully identified using phage display technology. The tumor target and antitumor effects have also been detected in different CD147-positive tumors in in vitro and in vivo assays, respectively. Meanwhile, it has a synergistic effect for inhibiting 4T1-bearing mice through conjugating doxorubicin. It may afford new strategies for cancer therapies.

Clinical value of echocardiography in evaluating hemodynamics and right ventricular function in patients with chronic thromboembolic pulmonary hypertension after balloon pulmonary angioplasty.

Background: Patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) are eligible for balloon pulmonary angioplasty (BPA). However, the short-term effects of BPA on pulmonary hemodynamics and right ventricular (RV) function in patients with CTEPH have not been elucidated. In the current study, echocardiography was conducted to explore the short-term effects of BPA on inoperable CTEPH patients. Methods: A total of 30 inoperable CTEPH patients who underwent echocardiography before and after BPA were enrolled to the present retrospective study. Right heart catheterization (RHC) parameters, echocardiography function parameters, and echocardiography structural parameters of patients were evaluated at baseline and within 24 hours after BPA and the results were compared. Results: RHC parameters including pulmonary artery systolic pressure (PASP), pulmonary artery diastolic pressure (PADP), mean pulmonary artery pressure (mPAP), and pulmonary vascular resistance (PVR), and echocardiography structural parameters including right atrium diameter (RAD), right ventricular end-diastolic area (RVEDA), right ventricular end-systolic area (RVESA), right atrium end-diastolic area (RAEDA) and right atrium end-systolic area (RAESA) significantly improved within 24 h after BPA compared with the baseline results (P<0.05). However, there were no significant differences in echocardiography function parameters including tissue Doppler-derived tricuspid lateral annular systolic velocity (S'), tricuspid annular plane systolic excursion (TAPSE), right ventricular index of myocardial performance (RIMP), right ventricular fractional area change (RVFAC) and left ventricular stroke volume (LVSV) before and after BPA. Conclusions: The findings show that a single BPA procedure significantly improves RV volume load and reduces the pulmonary blood pressure in CTEPH patients in the short-term. However, BPA does not improve RV systolic function 24 hours after the procedure. The results indicate that evaluation of RV structural and function with echocardiography is an effective approach for non-invasive monitoring of patient status after BPA.

A Novel Canine Mammary Cancer Cell Line: Preliminary Identification and Utilization for Drug Screening Studies.

Canine malignant mammary tumor is a dangerously fatal neoplastic disease with poor survival in female dogs. The aim of this study was to preliminary characterize a novel canine mammary cancer cell line, B-CMT, from canine primary mammary gland tumor, and to utilize it as a cell model for in vitro screening of possible therapeutic drugs. The successfully established cell line, B-CMT, was cultured over 50 passages. B-CMT has a fast proliferation rate, and a population doubling time (PDT) of 33.6 h. The B-CMT cell line lacked human epidermal growth factor receptor-2 (HER-2), estrogen receptors (ER) and progesterone receptors (PR) expression by qRT-PCR. Compared with MDCK cells, CDH1 expression of CMT cell line was significantly decreased or even absent, but GATA3 expression dramatically increased, while TGF-ß expression was at a similar level. Interestingly, the B-CMT cell line from canine primary tumor also showed positive hypoxia inducible factor-1α (HIF-1α) results in immunofluorescence (IF), western blot, and qRT-PCR analysis. Ten days post inoculation with EGFP-B-CMT (B-CMT cells stably expressing EGFP), the experimental mice developed palpable soft tissue masses which histologically resembled the canine primary tumor, and was approved to be derived from B-CMT cell line through detection of EGFP by immunohistochemical (IHC) analysis. Moreover, we investigated the cytotoxicity of five drugs to B-CMT cells, and the results showed that rapamycin and imatinib significantly inhibited the proliferation of the cells in vitro within a certain range of concentration. They also induced cell cycle arrest of B-CMT cells at G1 and G2 phase, respectively. In summary, the results of this report showed that B-CMT cell line might serve as a tool for future studies on tumor microenvironment and drug resistance.