Zn2+-interference and H2S-mediated gas therapy based on ZnS-tannic acid nanoparticles synergistic enhancement of cell apoptosis for specific treatment of prostate cancer.

Zn2+ and H2S are essential to maintain normal prostate function, and sometimes can evolve into weapons to attack and destroy prostate cancer (PCa) cells. Nevertheless, how to achieve the targeted and effective release of Zn2+ and H2S, and reverse the concentration distribution within PCa tumor cells still highly challenging. Herein, combined with these pathological characteristics of prostate, we proposed a tumor microenvironment (TME) responsive Zn2+-interference and H2S-mediated gas synergistic therapy strategy based on a nanoplatform of tannic acid (TA) modified zinc sulfide nanoparticles (ZnS@TA) for the specific treatment of PCa. Once the constructed pH-responsive ZnS@TA internalized by cancer cells, it would instantaneously decomposed in acidic TME, and explosively release excess Zn2+ and H2S exceeding the cell self-regulation threshold. Meanwhile, the in situ produced Zn2+ and H2S synergistic enhancement of cell apoptosis, which is evidenced to increase levels of Bax and Bax/Bcl-2 ratio, release of Cytochrome c in cancer cells, contributing to inhibit the growth of tumor. Moreover, the TA in cooperation with Zn2+ specifically limits the migration and invasion of PCa cells. Both in vitro and in vivo results demonstrate that the Zn2+-interference in combination with H2S-mediated gas therapy achieves an excellent anti-tumor performance. Overall, this nanotheranostic synergistic therapy provides a promising direction for exploring new strategies for cancer treatment based on specific tumor pathological characteristics, and provides a new vision for promoting practical cancer therapy.

Enhanced electrical conductivity and piezoresistive sensing in multi-wall carbon nanotubes/polydimethylsiloxane nanocomposites via the construction of a self-segregated structure.

Formation of highly conductive networks is essential for achieving flexible conductive polymer composites (CPCs) with high force sensitivity and high electrical conductivity. In this study, self-segregated structures were constructed in polydimethylsiloxane/multi-wall carbon nanotube (PDMS/MWCNT) nanocomposites, which then exhibited high piezoresistive sensitivity and low percolation threshold without sacrificing their mechanical properties. First, PDMS was cured and pulverized into 40-60 mesh-sized particles (with the size range of 250-425 µm) as an optimum self-segregated phase to improve the subsequent electrical conductivity. Then, the uncured PDMS/MWCNT base together with the curing agent was mixed with the abovementioned PDMS particles, serving as the segregated phase. Finally, the mixture was cured again to form the PDMS/MWCNT nanocomposites with self-segregated structures. The morphological evaluation indicated that MWCNTs were located in the second cured three-dimensional (3D) continuous PDMS phase, resulting in an ultralow percolation threshold of 0.003 vol% MWCNTs. The nanocomposites with self-segregated structures with 0.2 vol% MWCNTs achieved a high electrical conductivity of 0.003 S m-1, whereas only 4.87 × 10-10 S m-1 was achieved for the conventional samples with 0.2 vol% MWCNTs. The gauge factor GF of the self-segregated samples was 7.4-fold that of the conventional samples at 30% compression strain. Furthermore, the self-segregated samples also showed higher compression modulus and strength as compared to the conventional samples. These enhanced properties were attributed to the construction of 3D self-segregated structures, concentrated distribution of MWCNTs, and strong interfacial interaction between the segregated phase and the continuous phase with chemical bonds formed during the second curing process. These self-segregated structures provide a new insight into the fabrication of elastomers with high electrical conductivity and piezoresistive sensitivity for flexible force-sensitive materials.

Endocrine disruption of cadmium in rats using the OECD enhanced TG 407 test system.

OBJECTIVE: To evaluate the endocrine disrupting effects of cadmium (Cd) using OECD enhanced TG407 test guideline. METHODS: Sprague-Dawley (SD) rats were randomly divided into six groups and accordingly administered with 0, 1, 2.5, 5, 10, 20 mg/kg•BW/day of Cd by gavage for 28 days. Body weight, food consumption, hematology, biochemistry, sex hormone levels, urinary ß2-microglobulin, organ weights and histopathology and estrous cycle were detected. RESULTS: Cd could significantly decrease animals' body weight (P<0.05). Serum luteinizing hormone (LH) at 10-20 mg/kg•BW groups and testosterone (T) at 2.5 and 10 mg/kg•BW groups decreased significantly (P<0.05). However, no statistically significant change was found in urinary ß2-microglobulin among Cd-treatment groups (P>0.05). Endpoints related to female reproduction including uterus weight and histopathological change at 10-20 mg/kg•BW groups showed significant increase (P<0.05). While among male rats in 2.5, 10, 20 mg/kg•BW groups, weight of prostate, thyroids, and seminal vesicle glands significantly decreased (P<0.05). Moreover, no histopathological change was observed in kidney. CONCLUSION: Results suggested that Cd can cause endocrine disrupting effects in SD rats. Comparing with possible renal toxicity of Cd, its toxicity on endocrine system was more sensitive.