Shanshan Li,Long Zhang,Mingda Li,Jiao Huang,Baocheng Cui,Jie Jia,Zhaoming Guo,Kun Ma,Changhao Cui
B lymphoblastic leukemia (B-LL) is a clonal hematopoietic stem cell neoplasm derived from B-cell progenitors, which mainly occurs in children and adolescents and is one of the main causes of death from malignant tumors in this population. The surface marker CD19 is specifically expressed on the membrane of most malignant B-cells, which is widely used as a marker of B-LL antigen-specific immunotherapy . In this study, mesoporous titanium dioxide nanoparticles (MTNs)-based antibody drug delivery system was designed for B-LL treatment. Anti-CD19 monoclonal antibody was conjugated to PEGylated MTNs, and doxorubicin (DOX) was loaded in the nanoparticle . The CD19-PEG-MTN/DOX nanoparticle could recognize CD19 + B -LL cell lines and induced them apoptosis, but nontoxic for the normal cells. Further, after treated with CD19-PEG-MTN/DOX nanoparticle, pro-apoptotic proteins Bax and Caspase-3 in KOPN 8 and NALM-6 cells were significantly upregulated, but anti-apoptotic proteins Bcl2 , MCL-1, HSP 70, and BAG 3 were downregulated, which indicated the activation of the apoptosis pathway by the nanodrug. By contrast, CD19-PEG-MTN/DOX didn't play a part on CD19 − cell line U937. Besides, the cytotoxicity of CD19-PEG-MTN/DOX was low with good biocompatibility. Collectively, CD19-PEG-MTN/DOX is a promising antitumor nanodrug for the treatment of B-LL.
Ce Zhu,Miaomiao He,Juehan Wang,Yong Huang,Wei Deng,Limin Liu,Ganjun Feng,Li Zhang,Yueming Song
Photothermal therapy (PTT) is a desirable way to attain on-demand hyperthermia owing to the heat generated by photothermal materials absorbing near-infrared) light. The mild heat (42 ± 0.5 °C) can not only accelerate bone tissue regeneration but also promote the release of bioactive ions from biomaterials. Based on this one-stone-two-birds strategy, a 3D printed PEEK-graphene composite scaffold (PG) with hydroxyapatite (HA) coating (PGH) for photothermally remote control of bone regeneration was well designed in this study. The results showed that the HA coating on PGH could release Ca 2+ and PO 4 3– ions easily under NIR irradiation, which was ascribed to the mild heat generated from graphene in the composite scaffold. The mild heat and the boosted Ca 2+ /PO 4 3– release could synergistically enhance the bone regeneration ability both in vitro and in vivo . The underlying mechanism was further explored and confirmed to be closely related to the upregulation of HSP 70, by which the MAPK/ERK signaling pathway was activated selectively. The favorable results demonstrate that the 3D-printed PEEK/graphene composite scaffold is promising in the applications of bone defect repair.
Bolu Sun,Jinying Cai,Wuyan Li,Xiaodan Gou,Yuqiang Gou,Dai Li,Fangdi Hu
In this study, a novel electrochemical immunosensor for early screening of depression markers-heat shock protein 70 (HSP70) was successfully developed based on the porous graphene (PG) with huge specific surface area and excellent structure. Benefiting from the strong adsorption and good bioactivity of PG which was initially prepared via a simple pyrolysis process, a variety of heat shock protein70 (HSP70) can be firmly loaded on the PG to construct the basic electrode (HSP70/PG/GCE)，which was characterized by the cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), respectively. Due to the HSP70 fixed on the surface of basic electrode and the HSP70 in the samples can competitively combine with the horseradish peroxidase labeled human HSP 70 antibody (HRP-Strept-Biotin-Ab). As a result, it presented a negative correlation between the concentration of HSP70 in samples and the detection signal of the proposed electrochemical immunosensor (HRP-Strept-Biotin-Ab-HSP70/PG/GCE) in the test liquid. The application of PG with excellent electrical conductivity in construction of immunosensor remarkably improved the sensitivity of the immunosensor for detection of HSP70. The proposed immunosensor demonstrated a wide linear range of 0.0448 ~ 100 ng/mL with a low detection limit of 0.02 ng/mL at 3σ. Moreover, the proposed immunosensor could be applied for the sensitive and efficient detection of HSP70 in real samples with good precision, acceptable stability, reproducibility and satisfactory results. Therefore, the HSP70 immunosensor provides a novel and convenient method for early clinical screening of depression markers-heat shock protein 70.
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