bims-aporos 2018-10-21 papers

Issue of 2018–10–21
three papers selected by
Gavin McStay, Staffordshire University

Neurosci Lett. 2018 Oct 11. pii: S0304-3940(18)30696-7. [Epub ahead of print]

Synphilin-1 has neuroprotective effects on MPP+-induced Parkinson's disease model cells by inhibiting ROS production and apoptosis.

Takeo Shishido, Yoshito Nagano, Mutsuko Araki, Takashi Kurashige, Hitomi Obayashi, Takeshi Nakamura, Tetsuya Takahashi, Masayasu Matsumoto, Hirofumi Maruyama.

Synphilin-1, a cytoplasmic protein, interacts with α-synuclein which is one of the main constituents of Lewy bodies and plays an important role in the pathology of Parkinson's disease (PD), in neurons. This interaction indicates that synphilin-1 may also play a central role in PD. However, the biological functions of synphilin-1 are not fully understood, and whether synphilin-1 is neurotoxic or neuroprotective remains controversial. This study examined the function of synphilin-1 in a PD model in vitro. We used an inhibitor of mitochondrial complex I, 1-methyl-4-phenylpyridinium (MPP+). We established human neuroblastoma SH-SY5Y cell lines that stably expressed human synphilin-1. We found that overexpression of synphilin-1 increased SH-SY5Y cell viability after MPP+ treatment. We further found that synphilin-1 significantly suppressed apoptotic changes in nuclei, including nuclear condensation and fragmentation, after MPP+ treatment. We showed that synphilin-1 significantly decreased MPP+-induced cleaved caspase-3 and cleaved poly-ADP-ribose polymerase levels by using western blotting. Production of reactive oxygen species (ROS) induced by MPP+ was significantly reduced in cells expressing synphilin-1 compared to those expressing empty vector. Synphilin-1 inhibited MPP+-induced cytochrome c release from mitochondria into the cytosol. These data suggested that synphilin-1 may function to protect against dopaminergic cell death by preserving mitochondrial function and inhibiting early steps in the intrinsic apoptotic pathway. Taken together, our results indicated that synphilin-1 may play neuroprotective roles in PD pathogenesis by inhibiting ROS production and apoptosis.

Keywords: MPP(+); Parkinson’s disease; apoptosis; dopaminergic neurodegeneration; synphilin-1

DOI: https://doi.org/10.1016/j.neulet.2018.10.020

Colloids Surf B Biointerfaces. 2018 Oct 05. pii: S0927-7765(18)30703-3. [Epub ahead of print]173 335-345

A new drug carrier with oxygen generation function for modulating tumor hypoxia microenvironment in cancer chemotherapy.

Zhe Zhang, Na Niu, Xi Gao, Fuqin Han, Zhijun Chen, Shujun Li, Jian Li.

Hypoxia is the main characteristic of tumor microenvironment, and the one of the key factors that cause the drug resistance of cancer cells for chemotherapy. Anticancer drug such as DOX cannot react with sufficient oxygen to produce reactive oxygen species (ROS) in hypoxic environment, which affects the therapeutic efficiency of the drug. In this work, we constructed a multi-functional nano-carrier (named as FeSiAuO) containing Fe3O4, mesoporous SiO2 and Au2O3 with magnetic, large surface ratio and light induced oxygen production properties. The Au2O3 may decompose into oxygen (O2) and Au under the light irradiation to improve the oxygen concentration of the microenvironment of cancer cells, which increases the sensitivity of cancer cells to drug (DOX), reduces the drug resistance, and effectively exerts the anticancer effect of DOX. Meanwhile, the release of the as-loaded DOX molecule from the porous of SiO2 will be also promoted under light irradiation in diverse pH conditions. With the helping of the magnet effect of the Fe3O4, the DOX can be also targeted delivered to the tumor site under the magnetic field. All of above results were thoroughly examined by the cell and small animal assays, which demonstrate that the FeSiAuO can be served as the multifunctional drug nano-carrier to achieve the targeted high-efficient cancer therapy.

Keywords: Au(2)O(3); Chemotherapy; Drug release; Magnetic Fe(3)O(4); Oxygen generation function

DOI: https://doi.org/10.1016/j.colsurfb.2018.10.008

Acta Biomater. 2018 Oct 10. pii: S1742-7061(18)30602-0. [Epub ahead of print]

Transferrin/aptamer conjugated mesoporous ruthenium nanosystem for redox-controlled and targeted chemo-photodynamic therapy of glioma.

Xufeng Zhu, Hui Zhou, Yanan Liu, Yayu Wen, Chunfang Wei, Qianqian Yu, Jie Liu.

The blood-brain barrier (BBB) and low targeting are major obstacles for the treatment of gliomas. Accordingly, overcoming the BBB and enhancing the targeting of drugs to the glioma area are key to achieving a good therapeutic effect. Here, we have developed the mesoporous ruthenium nanosystem RBT@MRN-SS-Tf/Apt with dual targeting function. Transferrin (Tf) and aptamer AS1411(Apt) are grafted on the surfaces of mesoporous ruthenium nanoparticles (MRN) with high loading capacity. This is achieved via redox-cleavable disulfide bonds, serving as both a capping agent and a targeting ligand, enabling the effective penetration of the blood-brain barrier and targeting the glioma. In addition, RBT@MRN-SS-Tf/Apt can specifically kill glioma cells in vitro and in vivo. Moreover, anti-tumor drugs [Ru(bpy)2(tip)]2+ (RBT) will produce reactive oxygen species and induce apoptosis of tumor cells under laser irradiation, providing photodynamic therapy(PDT) for the treatment of gliomas, and further prolonging the median survival period. The study shows that this chemical photodynamic therapy nanosystem can be used as an efficient and powerful synergistic system for the treatment of brain tumors and other brain diseases of the central nervous system.
STATEMENT OF SIGNIFICANCE: In order to overcome the blood-brain barrier and low targeting, and enhance the anti-glioma activities of nanodrugs. We have developed RBT@MRN-SS-Tf/Apt with dual targeting function.It is achieved release drug via redox-cleavable disulfide bonds, and enable the effective penetration of the blood-brain barrier and targeting the glioma. Moreover, anti-tumor drugs RBT will produce reactive oxygen species and induce apoptosis of tumor cells under laser irradiation, providing photodynamic therapy(PDT)for the treatment of gliomas, and further prolonging the median survival period. Therefore, this chemical photodynamic therapy nanosystem can be used as an efficient and powerful synergistic system for the treatment of brain tumors and other brain diseases of the central nervous system.

Keywords: AS1411; Dual targeting; Glioma; PDT; Redox; Response; Tf

DOI: https://doi.org/10.1016/j.actbio.2018.10.012