Stem Cell Research & Therapy
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2022
·Vol. 13
·期 1
·1-15
·
IF 8.079
Liu Fengyi,Wang Xu,Li Yuzhou,Ren Mingxing,He Ping,Wang Lu,Xu Jie,Yang Sheng,Ji Ping
Background Cartilage defects pose a significant burden on medical treatment, leading to an urgent need to develop regenerative medicine approaches for cartilage repair, such as stem cell therapy. However, the direct injection of stem cells can result in insufficient delivery or inaccurate differentiation. Hence, it is necessary to choose appropriate stem cell delivery scaffolds with high biocompatibility, injectability and chondral differentiation induction ability for cartilage regeneration.Methods In this study, the photocrosslinked gelatin methacrylate (GelMA) hydrogel with high cell affinity and plasticity was selected and strengthened by incorporating methacrylic anhydride-modified poly(amidoamine) (PAMAM-MA) to fabricate an adipose-derived stromal/stem cells (ASCs) delivery scaffold for cartilage repair. The physiochemical properties of the GelMA/PAMAM-MA hydrogel, including the internal structure, stability and mechanical properties, were tested. Then, ASCs were encapsulated into the hydrogels to determine the in vitro and in vivo chondrogenic differentiation induction abilities of the GelMA/PAMAM-MA hydrogel.Results Compared with the GelMA hydrogel, the GelMA/PAMAM-MA hydrogel exhibited more uniform structure, stability and mechanical properties. Moreover, on the basis of good biocompatibility, the hybrid hydrogel was proven to exert a sufficient ability to promote cartilage regeneration by in vitro three-dimensional (3D) culture of rASCs and in vivo articular cartilage defect repair.Conclusion sThe injectable photocrosslinked GelMA/PAMAM-MA hydrogel was proven to be a capable stem cell carrier for cartilage repair and provides new insight into the design strategy of stem cell delivery scaffolds.
研究领域:
再生医学
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组织工程
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干细胞生物学
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生物医学材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Desalination and Water Treatment
·
2024
·
IF 1
Chaojie Cai,Xiaobin Lei,Xinzhen Zhao,Lin Wang,Jizhen Jia,Changkun Liu
ABSTRACT Modification of the active layer is an effective method to improve the separation performance of the thin-film composite forward osmosis (FO) membranes. In this paper, the dendrimer polyamidoamine (PAMAM) was in-situ integrated into the polyamide (PA) active layer via the interfacial polymerization. The separation performance results showed that the addition of PAMAM significantly improved the separation water flux of the modified FO membrane by 1.7 times, and the reverse salt flux was almost unchanged. In addition, the removal efficiency of the modified FO membrane for heavy metal ions was enhanced, with the rejection rates of various heavy metal ions all higher than 99.6%, and the corresponding water flux was also significantly enhanced. The PAMAM integrated with the active layer contained a large number of hydrophilic segments and terminal amine groups, which in situ enhanced the hydrophilicity and permeability of the active layer, and further improved the removal of heavy metal ions based on the coordination and electrostatic repulsion effects. The purpose of this paper is to provide a feasible way to improve the practical application performance of the FO membranes.
研究领域:
环境工程
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材料科学
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水处理技术
✓ 已验证
DOI
高影响因子
Nanoscale
·
2019
·Vol. 11
·期 42
·20030-20044
·
IF 6.97
Lin Hou,Dandan Chen,Lisha Hao,Chunyu Tian,Yingshan Yan,Ling Zhu,Huijuan Zhang,Yi Zhang,Zhenzhong Zhang
Cancer-associated fibroblasts (CAFs) are important barriers for nanoparticles (NPs) to deeply penetrate into tumors and severely limit the antitumor efficacy of nanomedicines. Herein, we proposed a CAF-triggered transformable drug delivery system based on a cleavable peptide responsive to fibroblast activation protein-α (FAP-α) specifically overexpressed on the surface of CAFs. The NPs were composed of cationic poly(amidoamine) (PAMAM) dendrimers cross-linked by our designed peptide, a chemotherapeutical drug was incorporated onto PAMAM using disulfide bonds and finally, hyaluronic acid (HA) was conjugated to improve the tumor targetability as well as biocompatibility through electrostatic interactions. These NPs had an initial size of ∼200 nm and negative zeta potential favorable for stable blood circulation; however, after docking with CAFs, they dissociated into smaller NPs and exposed the relative positive surface charge to facilitate penetration and enter the tumor cells together with CAFs. An interesting finding was that this system intracellularly released different levels of drugs in these two kinds of cells, which was beneficial for the disruption of the stromal barrier and increasing the local drug accumulation. Our investigation confirmed that the constructed system could alleviate the biological barriers and hold promising therapeutic efficiency for desmoplastic solid tumors.
研究领域:
纳米技术
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肿瘤学
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药学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2016
·
IF 7.476
Bing Zhang,Chuanmin Ding
The sensitive determination of carcino embryonie antigen (CEA)-a set of highly related glycoproteins involved in cell adhesion-is beneficial to the early diagnosis of colorectal cancer. In this study, a novel displacement-type amperometric immunosensing platform, based on the fact that glucose and Alizarin Red S (ARS) compete for phenylboronic acid bindng sites, was projected for sensitive detection of tumour marker (CEA, used as a model) on a PAMAM dendrimer-encapsulated nanogold (PAMAM-Au)-functionlized sensing interface. Firstly, 4 − mercaptophenylboronic acid (S-PBA) was assembled onto the PAMAM-Au via the S-Au interaction, and then ARS was immobilized by S-PBA binding of cis-diol moieties, which was dropped on the surface of glassy carbon electrode as sensing platform to combine antibody. Meanwhile, amylase modified gold nanoparticles were employed as labels. Accompanying the sandwich immunoassay , the carried amylase could hydrolyze amylose into glucose, and the displacement-type format was triggered due to the stronger adhesion between glucose and PBA, which resulted in the change of electrochemical signals due to the decrease of ARS (as an electron mediator). Under optimal conditions, the SWV signals were related to the concentration of CEA, indicating a certain proportional relation in a range of 0.01~50 ng mL −1 with a detection limit (LOD) of 0.003 ng mL −1 . Intra- and inter-assay coefficients of variation were below 10%, respectively. In addition, the methodology showed good accordance with a commercialized enzyme-linked immunosorbent assay (ELISA) method.
研究领域:
生物化学
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分析化学
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癌症诊断
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电化学传感
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2017
·
IF 4.233
Yan Gao,Yiwei Zhang,Yuming Zhou,Chao Zhang,Hongxing Zhang,Shuo Zhao,Jiasheng Fang,Mengqiu Huang,Xiaoli Sheng
In this work, we report a feasible approach to synthesize a ternary nanocomposites , Pt/lanthanum doped mesoporous zirconium oxide (Pt/La 2 O 3 -ZrO 2 ), via an effective two-step method. Ordered mesoporous La 2 O 3 -ZrO 2 composites were firstly fabricated with mesoporous silica KIT-6 as a hard template. Subsequently, uniform Pt nanoparticles encapsulated by 4 hydroxyl-terminated poly (amidoamine) (G4-OH PAMAM) dendrimers were deposited on the La 2 O 3 -ZrO 2 composites. The as-prepared samples were characterized by transmission electron microscope (TEM), N 2 adsorption–desorption isotherm analysis, energy dispersion X-ray analysis (EDX), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and temperature programmed reduction (H 2 -TPR). The average size of PtDENs was found to be 1.48 nm in diameter. Furthermore, the introduction of La could improve the structure of the supports which was confirmed by XRD and H 2 -TPR analysis. The reduction of p-nitrophenol to p-aminophenol by NaBH 4 was utilized to evaluate the catalytic performances of catalysts. Results indicated that the Pt/La 2 O 3 -ZrO 2 catalyst calcined in nitrogen at 550 °C exhibited the highest catalytic performance and still kept the high catalytic activity even after six cycles. This phenomenon suggests that synergistic effect among Pt-Zr-La could enhance the catalytic efficiency. Finally, reaction mechanism was proposed for the reduction of p-nitrophenol.
研究领域:
材料科学
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催化
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纳米技术
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化学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2017
·
IF 6.319
Wenqi Chen,Yong Liu,Xiao Liang,Yu Huang,Quanshun Li
Chondroitin sulfate (CS) was modified on a polyamidoamine dendrimer (PAMAM) through Michael addition to construct a tumor-targeted carrier CS-PAMAM for miR-34a delivery. The derivative CS-PAMAM was demonstrated to achieve an efficient cellular uptake of miR-34a in a CD44-dependent endocytosis way and further facilitate the endosomal escape of miR-34a after 4 h. Through the miR-34a delivery, obvious inhibition of cell proliferation could be detected which was attributed to the enhancement of cell apoptosis and cell cycle arrest , and meanwhile the cell migration and invasion has been observed to be inhibited. Finally, the intravenous injection of CS-PAMAM/miR-34a formulation into mice bearing human lung adenocarcinoma cell A549 xenografts could efficiently inhibit the tumor growth and induce the tumor apoptosis owing to the enhanced accumulation of miR-34a in tumor tissue. Overall, CS-PAMAM is potential to be used as a tumor-targeted oligonucleotide carrier for achieving tumor gene therapy. Statement of Significance The cationic dendrimer PAMAM was modified by chondroitin sulfate (CS) through Michael addition to construct a tumor-targeted carrier CS-PAMAM for miR-34a delivery. The introduction of CS could achieve an efficient cellular uptake and intracellular transfection of miR-34a in a CD44-dependent endocytosis manner. The miR-34a delivery could execute the anti -proliferation activity by simultaneously inducing cell apoptosis and cell cycle arrest, and also the anti -migration activity. The CS-PAMAM-mediated systemic delivery of miR-34a showed significant inhibition of tumor growth and induction of tumor apoptosis using a mice model of subcutaneously implanted tumors.
研究领域:
药学
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分子生物学
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癌症研究
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Qi-Song Tong,Hua Huang,Hui-Han Yu,Rong Liu,Song Shen,Jin-Zhi Du
Remodeling the immunosuppressive tumor microenvironment (TME) by immunomodulators has been well studied in the past years. However, strategies that enable concurrent modulation of both the immunosuppressive TME and tumor-draining lymph nodes (TDLNs) are still in the infancy. Here, we report a pH-sensitive size-switchable nanocluster, SPN-R848, to achieve simultaneous accumulation in tumor and TDLNs for immune activation. SPN-R848 with original size around 150 nm was formed by self-assembly of resiquimod (R848)-conjugated polyamidoamine (PAMAM) derivative, which could disintegrate into its small constituents (～ 8 nm) upon exposure to tumor acidity. The size reduction not only enhanced their accumulation and perfusion in the primary tumor, but promoted their transport and distribution in TDLNs. Accordingly, SPN-R848 remarkably remodeled the immunosuppressive TME by polarizing M2 to M1 macrophages and activated dendritic cells (DCs) in TDLNs, which synergistically facilitated the production and stimulation of cytotoxic T cells, and inhibited tumor growth in breast cancer and melanoma mouse models. Our study suggests that co-activation of immune microenvironments in both tumor and TDLNs may represent a promising direction to elicit strong antitumor immunity.
研究领域:
癌症生物学
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免疫学
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纳米技术
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE
·
2020
·Vol. 56
·期 6
·4380-4395
·
IF 3.553
Li Lin,Zhang Peng,Yang Xiucheng,Li Congcong,Guo Yan,Sun Kaoxiang
Abstract A receptor-mediated, active-targeting and glutathione (GSH) turn-on charge-reversal core/shell nanocomplex HA-MEA-s-s-TGA/PAMAM@DOX was constructed to achieve increased stability, improved cellular uptake, facilitated endo-lysosomal escape and enhanced antitumor efficacy. This nanocomplex was composed of anionic hyaluronic acid (HA)-graft GSH-sensitive HA-MEA-s-s-TGA as the outer shell and the cationic PAMAM@DOX core with encapsulated doxorubicin (DOX) into the hydrophobic cavities of polyamidoamine (PAMAM) dendrimers. We hypothesized that the anionic outer layer could promote cellular uptake of HA-MEA-s-s-TGA/PAMAM@DOX by HA receptor-mediated endocytosis. After internalization into tumor cells, the outer shell of the internalized nanocomplex was disassembled in endo-lysosomes via the destruction of disulfide linkages to re-expose PAMAM drug core. This action induced release of the encapsulated DOX and facilitated endo-lysosomal escape through the synergistic action of the proton sponge effect and cationic–anionic interaction between protonated PAMAM and endo-lysosome membranes. In vitro release profiles demonstrated the intracellular environment-responsive release behavior of DOX from this nanocomplex, with a cumulative release of 80% within 4 days in a simulated tumor intracellular microenvironment, whereas the surface charge changed from − 18.82 mV to + 10.95 mV. The MTT assay revealed the good biocompatibility of the negatively charged nanocomplex and efficient toxicity against HeLa cells. The designed pH/GSH dual-responsive nanocomplex could be an efficacious and safe delivery platform for cancer therapy. Graphical abstract
研究领域:
纳米技术
·
药学
·
癌症治疗
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2021
·
IF 8.128
Junzong Chen,Miaojuan Qiu,Shiqiang Zhang,Binbin Li,Dong Li,Xiuyu Huang,Zhirong Qian,Jing Zhao,Zhiyong Wang,Di Tang
Calcium based biomaterials were widely used for drug delivery application due to their biodegradability, biocompatibility, and high drug loading capacity. Herein, amino-capped polyamidoamine (PAMAM) dendrimer was applied as a macromolecular template to form amino-modified calcium phosphate hollow sphere (CaPO-NH 2 ). After loading with 5-fluorouracil (5Fu), this system performed synergistic cancer chemotherapy. In this study, the 5Fu/CaPO-NH 2 particles could be efficiently uptaken by cancer cells, and then decompose into Ca 2+ and release 5Fu drug in the cytoplasm; therefore calcium overload and reactive oxygen species (ROS) accumulation were found in PSN1 cells that could induce cell membrane damage and elicit cell apoptosis through a series of biochemical reactions including endoplasmic reticulum stress, lipid peroxidation and mitochondrial apoptosis. In the PSN1 pancreatic cancer xenograft model, the 5Fu/CaPO-NH 2 system performed high tumor inhibition via chemotherapy and calcium overload induced apoptosis. Comparingly, the normal cells and organs were insensitive to this synergistic therapy, which indicated the well biocompatibility of delivery system. Thus, this study provided a promising CaPO-NH 2 drug delivery platform for enhanced 5Fu chemotherapeutic effect.
研究领域:
药学
·
生物医学工程
·
癌症治疗
·
药物递送系统
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Yang Liu,Xiaoting Chen,Xueqin Tan,Yeqian Huang,Wen Zhang,Zhicun Wang,Li Yang,Yunbing Wang,Zhengyong Li,Xingdong Zhang
Microtia profoundly affects patients' appearance and psychological well-being. Tissue engineering ear cartilage scaffolds have emerged as the most promising solution for ear reconstruction. However, constructing tissue engineering ear cartilage scaffolds requires multiple passaging of chondrocytes, resulting in their dedifferentiation and lose their special phenotypes and functions. To tackle these issues, here we employ guanidinobenzoic acid (GBA) modified Generation 5 Polyamidoamine (PAMAM) dendrimers (PG) as Runx1 plasmid carrier to construct PG/pRunx1 polyplex nanoparticles. The PG/pRunx1 polyplexes are transfected into human auricular chondrocytes, significantly mitigating chondrocyte dedifferentiation and enhancing cartilage regeneration during the in vitro culture. Furthermore, we develop a highly porous double-network hydrogels based on methacrylate-functionalized and oxidized chondroitin sulfate and carbohydrazide-modified gelatin and the hydrogels possessed both dynamic adaptability and mechanical support characteristics by reversible dynamic covalent crosslinking and static covalent crosslinking, serving as an ideal scaffold for tissue engineering. Consequently, chondrocytes treated with PG/pRunx1 polyplex nanoparticles are incorporated into the hydrogels to construct tissue-engineered auricular cartilage scaffolds. After subcutaneous implantation in nude mice, the scaffolds containing chondrocytes treated with PG/pRunx1 nanoparticles showed more mature cartilaginous tissue, characterized by prominent ECM deposition and enhanced chondrogenesis. Therefore, this research provides a novel strategy for the development of tissue-engineered auricular cartilage scaffolds.
研究领域:
组织工程
·
再生医学
·
生物材料
·
生物医学工程
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）