Biomaterials Science
·
2017
·Vol. 5
·期 11
·2268-2275
·
IF 4.21
Haobo Han,Jiebing Yang,Yudi Wang,Wenqi Chen,Jiawen Chen,Yan Yang,Quanshun Li
The nucleobase analogue 2-amino-6-chloropurine was modified on the surface of polyamidoamine (PAMAM) to construct a derivative AP-PAMAM, and then it was used as a gene carrier for miR-23b delivery to achieve the anti-tumor effects. The carrier AP-PAMAM could condense miR-23b into stable nanoparticles with a particle size of 97.3 nm (N/P ratio of 50), which was favorable for the cellular uptake of nanoparticles. Compared with PAMAM, AP-PAMAM exhibited an obviously enhanced transfection efficiency through the transfection assay of plasmids pEGFP-N3 and pGL-3. Using the human lung adenocarcinoma cell line A549 as a model, AP-PAMAM-mediated miR-23b delivery could achieve a stronger anti-proliferative effect than PAMAM/miR-23b. The inhibition of cell proliferation was elucidated to be associated with the apoptotic induction (apoptotic ratio of 23.2%) and S phase arrest owing to the decreased expression level of cyclin D1. Meanwhile, the AP-PAMAM-mediated miR-23b delivery could suppress the cell migration and invasion of cancer cells through wound healing and Transwell migration assays. In summary, the PAMAM derivative-mediated miR-23b delivery could be a promising strategy for achieving tumor gene therapy.
研究领域:
药学
·
分子生物学
·
癌症研究
·
基因治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-20
·
IF 16.6
Han Haobo,Xing Jiakai,Chen Wenqi,Jia Jiaxin,Li Quanshun
In rheumatoid arthritis (RA), insufficient apoptosis of macrophages and excessive generation of pro-inflammatory cytokines are intimately connected, accelerating the development of disease. Here, a fluorinated polyamidoamine dendrimer (FP) is used to deliver miR-23b to reduce inflammation by triggering the apoptosis of as well as inhibiting the inflammatory response in macrophages. Following the intravenous injection of FP/miR-23b nanoparticles in experimental RA models, the nanoparticles show therapeutic efficacy with inhibition of inflammatory response, reduced bone and cartilage erosion, suppression of synoviocyte infiltration and the recovery of mobility. Moreover, the nanoparticles accumulate in the inflamed joint and are non-specifically captured by synoviocytes, leading to the restoration of miR-23b expression in the synovium. The miR-23b nanoparticles target Tab2 , Tab3 and Ikka to regulate the activation of NF-κB pathway in the hyperplastic synovium, thereby promoting anti-inflammatory and anti-proliferative responses. Additionally, the intravenous administration of FP/miR-23b nanoparticles do not induce obvious systemic toxicity. Overall, our work demonstrates that the combination of apoptosis induction and inflammatory inhibition could be a promising approach in the treatment of RA and possibly other autoimmune diseases.
研究领域:
药理学
·
免疫学
·
风湿病学
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2024
·
IF 10.7
Boyu Xiong,Xinxin Shao,Guangxu Fang,Mengmeng Dong,Haobo Han,Quanshun Li
Herein, porous poly(lactic-co-glycolic acid) (PLGA) microspheres were prepared to load icariin and miR-23b for the treatment of metastatic lung cancer. The microspheres exhibited desirable aerodynamic diameter, high drug loading and encapsulation efficiency, as well as a favorable drug release profile, which was beneficial for the deposition and exposure of drugs in the lung tissues. The release solution from microspheres exhibited a favorable anti-proliferative effect by inducting cell apoptosis and arresting the cell cycle at G1 phase, and meanwhile inhibited the migration and invasion of cancer cells. More importantly, the microspheres could be effectively inhaled and accumulated in the lung tissues to trigger the in situ apoptosis of tumor cells and suppress metastasis, using mice bearing melanoma-metastatic lung cancer as a model. Furthermore, inhalation of the microspheres showed good favorable biocompatibility, barely causing tissue damage. Overall, porous PLGA microspheres provide a promising platform for the inhalable co-delivery of drugs and genes to obtain ideal therapeutic efficacy in lung cancer and other pulmonary diseases.
研究领域:
药学
·
肿瘤学
·
生物技术
·
肺科学
✓ 已验证
产品关联
DOI
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2021
·Vol. 21
·期 5
·2100024
·
IF 4.979
Sihan Wang,Jiakai Xing,Boyu Xiong,Haobo Han,Min Hu,Quanshun Li
Emerging evidence suggests that microRNAs (miRNAs) play key roles in the regulation of multiple biological processes, including the differentiation of osteoblasts. Although miRNA-based gene therapy holds immense potential in the treatment of a variety of diseases, the intracellular delivery of miRNA remains challenging owing to the lack of efficient and safe gene carriers. In this study, a fluoropolymer (FP) is constructed through the modification of polyamidoamine (PAMAM) using heptafluorobutyric anhydride and then is used as a carrier for miR-23b transfection to induce osteocyte differentiation of osteoblasts. The derivative FP is found to facilitate miR-23b transfection due to its favorable endosomal escape from the "proton sponge" effect. Compared to PAMAM/miR-23b, the FP/miR-23b nanocomplex efficiently promotes the differentiation of osteoblasts and formation of calcified nodules, attributable to enhanced expression of various osteogenesis genes (runt-related transfection factor 2 [RUNX2], alkaline phosphatase [ALP], osteopontin [OPN], and osteocalcin [OCN]). Thus, FP-mediated miR-23b transfection may be used as an effective strategy to facilitate osteogenic differentiation.
研究领域:
生物材料
·
分子生物学
·
基因治疗
·
组织工程
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）