Bionic natural small molecule co-assemblies towards targeted and synergistic Chemo/PDT/CDT

Shiyao Fu,Mingao Wang,Bin Li,Xu Li,Jianjun Cheng,Haitian Zhao,Hua Zhang,Aijun Dong,Weihong Lu,Xin Yang 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

Background Multi-component nano-delivery systems based on chemotherapy (chemo)- photodynamic therapy (PDT)- chemodynamic therapy (CDT) have gained increased attention as a promising strategy to improve clinical outcomes in cancer treatment. However, there remains a challenge in developing biodegradable, biocompatible, less toxic, yet highly efficient multicomponent nanobased drug delivery systems (DDS). Here, our study presents the screening and development of a novel DDS based on co-assemblies natural small molecule (NSMs). These molecules (oleanolic acid, and betulinic acid) are combined with photosensitizers Chlorine6 (Ce6) and Cu2+ that are encapsulated by tumor cell membranes. This nanocarrier encapsulated in tumor cell membranes achieved good tumor targeting and a significant improvement in tumor accumulation. Methods A reprecipitation method was used to prepare the co-assembled nanocarrier, followed by the introduction of Cu2 + into the DDS (OABACe6 NPs). Then, by wrapping the surface of NPs with the cell membranes of 4T1 which is a kind of mouse breast cancer cells (CM@OABACe6/Cu NPs). and analysis of its structure and size distribution with UV– Vis, XPS, FT-IR, SEM, TEM, and DLS. The synergistic effects of in vitro chemotherapy, CDT and PDT and targeting were also validated by cellular and animal studies. Results It was shown that CM@OABACe6/Cu NPs achieved good tumor targeting and a significant improvement in tumor accumulation. In the composite nano-assembly, the NSMs work together with the Ce6 to provide effective and safe chemo and PDT. Moreover, the effect of reduced PDT due to the depletion of reactive oxygen species (ROS) by excess glutathione (GSH) in the tumor can be counteracted when Cu2 + is introduced. More importantly, it also confers CDT through a Fenton-like catalytic reaction with H2O overexpressed at the tumor site. Conclusions By constructing CM@OABACe6/Cu NPs with homologous targeting, we create a triple synergistic platform for cancer therapy using PDT, chemo, and CDT. We propose here a novel combinatorial strategy for designing more naturally co-assembled small molecules, especially for the development of multifunctional synergistic therapies that utilize NSMs.

Modification of activated carbon from agricultural waste lotus leaf and its adsorption mechanism of beryllium

Xu Zhao,Yucheng Su,Hongqiang Wang,Zhiwu Lei,Eming Hu,Fang Hu,Qingliang Wang,Lechang Xu,Shiyao Fan,Xinwei Liu,Xuanzhang Hao 한국화학공학회 2023 Korean Journal of Chemical Engineering Vol.40 No.1

With the wide application of beryllium globally, industrial wastewater has rapidly increased. Previously, adsorption was effective in treating this issue. However, most adsorbents have a poor removal rate, primarily in the low adsorption capacity. To remove Be from industrial wastewater and overcome the disadvantages of low adsorption capacity and poor removal rate of existing adsorbents, typical agricultural waste lotus leaf was used to prepare Al-activated carbon (Al-AC) by the impregnation-calcination modification of Al(NO3)3. The theoretical maximum adsorption capacity of Al-AC was 32.86 mg/g. Langmuir, Freundlich, and Temkin models were used to thermodynamically analyze Al-AC, and adsorption thermodynamics demonstrated that the adsorption reaction of Al-AC was endothermic. Through characterization analysis, the specific surface area of the modified AC increased from 4.3573 to 155.87 m2/g. This study provides a new approach to preparing and modifying AC and a new method for removing Be from industrial wastewater.

The Integrins Involved in Soybean Agglutinin-Induced Cell Cycle Alterations in IPEC-J2

Pan, Li,Zhao, Yuan,Yuan, Zhijie,Farouk, Mohammed Hamdy,Zhang, Shiyao,Bao, Nan,Qin, Guixin Korean Society for Molecular and Cellular Biology 2017 Molecules and cells Vol.40 No.2

Soybean agglutinin (SBA) is an anti-nutritional factor of soybean, affecting cell proliferation and inducing cytotoxicity. Integrins are transmembrane receptors, mediating a variety of cell biological processes. This research aims to study the effects of SBA on cell proliferation and cell cycle progression of the intestinal epithelial cell line from piglets (IPEC-J2), to identify the integrin subunits especially expressed in IPEC-J2s, and to analyze the functions of these integrins on IPEC-J2 cell cycle progression and SBA-induced IPEC-J2 cell cycle alteration. The results showed that SBA lowered cell proliferation rate as the cell cycle progression from G0/G1 to S phase (P < 0.05) was inhibited. Moreover, SBA lowered mRNA expression of cell cycle-related gene CDK4, Cyclin E and Cyclin D1 (P < 0.05). We successfully identified integrins ${\alpha}2$, ${\alpha}3$, ${\alpha}6$, ${\beta}1$, and ${\beta}4$ in IPEC-J2s. These five subunits were crucial to maintain normal cell proliferation and cell cycle progression in IPEC-J2s. Restrain of either these five subunits by their inhibitors, lowered cell proliferation rate, and arrested the cells at G0/G1 phase of cell cycle (P < 0.05). Further analysis indicated that integrin ${\alpha}2$, ${\alpha}6$, and ${\beta}1$ were involved in the blocking of G0/G1 phase induced by SBA. In conclusion, these results suggested that SBA lowered the IPEC-J2 cell proliferation rate through the perturbation of cell cycle progression. Furthermore, integrins were important for IPEC-J2 cell cycle progression, and they were involved in the process of SBA-induced cell cycle progression alteration, which provide a basis for further revealing SBA anti-proliferation and anti-nutritional mechanism.

The Integrins Involved in Soybean Agglutinin-Induced Cell Cycle Alterations in IPEC-J2

Li Pan,Yuan Zhao,Zhijie Yuan,Mohammed Hamdy Farouk,Shiyao Zhang,Nan Bao,GuiXin Qin 한국분자세포생물학회 2017 Molecules and cells Vol.40 No.2

Soybean agglutinin (SBA) is an anti-nutritional factor of soybean, affecting cell proliferation and inducing cytotoxicity. Integrins are transmembrane receptors, mediating a variety of cell biological processes. This research aims to study the effects of SBA on cell proliferation and cell cycle progression of the intestinal epithelial cell line from piglets (IPEC-J2), to identify the integrin subunits especially expressed in IPEC-J2s, and to analyze the functions of these integrins on IPEC-J2 cell cycle progression and SBA-induced IPEC-J2 cell cycle alteration. The results showed that SBA lowered cell proliferation rate as the cell cycle progression from G0/G1 to S phase (P < 0.05) was inhibited. Moreover, SBA lowered mRNA expression of cell cycle-related gene CDK4, Cyclin E and Cyclin D1 (P < 0.05). We successfully identified integrins 2, 3, 6, 1, and 4 in IPEC-J2s. These five subunits were crucial to maintain normal cell proliferation and cell cycle progression in IPEC-J2s. Restrain of either these five subunits by their inhibitors, lowered cell proliferation rate, and arrested the cells at G0/G1 phase of cell cycle (P < 0.05). Further analysis indicated that integrin 2, 6, and 1 were involved in the blocking of G0/G1 phase induced by SBA. In conclusion, these results suggested that SBA lowered the IPEC-J2 cell proliferation rate through the perturbation of cell cycle progression. Furthermore, integrins were important for IPEC-J2 cell cycle progression, and they were involved in the process of SBA-induced cell cycle progression alteration, which provide a basis for further revealing SBA anti-proliferation and anti-nutritional mechanism.

An Efficient Markerless Deletion System Suitable for the Industrial Strains of Streptomyces

( Jianxin Dong ),( Jiaxiu Wei ),( Han Li ),( Shiyao Zhao ),( Wenjun Guan ) 한국미생물 · 생명공학회 2021 Journal of microbiology and biotechnology Vol.31 No.12

The genus Streptomyces is intensively studied due to its excellent ability to produce secondary metabolites with diverse bioactivities. In particular, adequate precursors of secondary metabolites as well as sophisticated post modification systems make some high-yield industrial strains of Streptomyces the promising chassis for the heterologous production of natural products. However, lack of efficient genetic tools for the manipulation of industrial strains, especially the episomal vector independent tools suitable for large DNA fragment deletion, makes it difficult to remold the metabolic pathways and streamline the genomes in these strains. In this respect, we developed an efficient deletion system independent of the episomal vector for large DNA fragment deletion. Based on this system, four large segments of DNA, ranging in length from 10 kb to 200 kb, were knocked out successfully from three industrial Streptomyces strains without any marker left. Notably, compared to the classical deletion system used in Streptomyces, this deletion system takes about 25% less time in our cases. This work provides a very effective tool for further genetic engineering of the industrial Streptomyces.