Ultrasmall Bi/Cu Coordination Polymer Combined with Glucose Oxidase for Tumor Enhanced Chemodynamic Therapy by Starvation and Photothermal Treatment.

Multi-modal combination therapy for tumor is expected to have superior therapeutic effect compared with monotherapy. In this study, a super-small bismuth/copper-gallic acid coordination polymer nanoparticle (BCN) protected by polyvinylpyrrolidone is designed, which is co-encapsulated with glucose oxidase (GOX) by phospholipid to obtain nanoprobe BCGN@L. It shows that BCN has an average size of 1.8 ± 0.7 nm, and photothermal conversion of BCGN@L is 31.35% for photothermal imaging and photothermal therapy (PTT). During the treatment process of 4T1 tumor-bearing nude mice, GOX catalyzes glucose in the tumor to generate gluconic acid and hydrogen peroxide (H2 O2 ), which reacts with copper ions (Cu2+ ) to produce toxic hydroxyl radicals (•OH) for chemodynamic therapy (CDT) and new fresh oxygen (O2 ) to supply to GOX for further catalysis, preventing tumor hypoxia. These reactions increase glucose depletion for starvation therapy , decrease heat shock protein expression, and enhance tumor sensitivity to low-temperature PTT. The in vitro and in vivo results demonstrate that the combination of CDT with other treatments produces excellent tumor growth inhibition. Blood biochemistry and histology analysis suggests that the nanoprobe has negligible toxicity. All the positive results reveal that the nanoprobe can be a promising approach for incorporation into multi-modal anticancer therapy.

[Effects of different intensity exercise training on apoptosis-related microRNAs and the targeted proteins in cardiomyocytes].

OBJECTIVE: To detect the levels of miR-1, miR-21 and their targeted proteins in hearts of mice after different exercise training, and discuss potential molecular mechanism. METHODS: Male C57BL/6 mice were randomly divided to 3 groups:sedentary (SE), exercise training 1(ET1) and exercise training 2 (ET2). SE did not do any exercise; ET1 undertook swimming training for 8 weeks, once a day, 5 days/week. Swimming 30 min in the 1st week, and the duration was increased 10 min per week to 90 min and maintained in the 7th and 8th week. ET2 performed the same work as ET1 and switched to twice a day by the end of the 5th week. TUNEL assay was applied to test myocardial apoptosis. Western blot and RT-PCR were used to detect proteins and miRs levels respectively. RESULTS: Compared with SE, in ET1, myocardial apoptosis and miR-1 level did not change, but its targeted protein Bcl-2 increased significantly(P<0.01). miR-21 and its targeted protein PDCD4 did not change significantly. In ET2, myocardial apoptosis and miR-1 level were decreased significantly(P<0.05). Bcl-2 was increased significantly(P<0.01). miR-21 also increased significantly (P<0.05), but PDCD4 did not decrease significantly. CONCLUSIONS: Exercise training in ET2 other than ET1 could down-regulate myocardial apoptosis. Alterations of miR-1 and Bcl-2 may be responsible for this cardioprotection. PDCD4 is not sensitive to exercise training, it is likely that miR-21 and other targeted proteins participate in exercise-regulative apoptosis.