Fucoidan-based micelles as P-selectin targeted carriers for synergistic treatment of acute kidney injury

Gao, Shu; Chen, Lu; Wang, Zhixian; Du, Yuyin; Xu, Xiaoling; Xu, Min; Zhao, Zhongwei; Chen, Minjiang; Dai, Yiyang; Weng, Qiaoyou; Fang, Shiji; Fan, Kai; Liu, Di; Du, Yong‐Zhong; Ji, Jiansong

doi:10.1016/j.nano.2020.102342

Cited by 17 publications

(12 citation statements)

References 37 publications

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“…Previous experiments have focused on combining fucoidan in a therapeutic system to obtain gatekeeper [ 50 ], target molecule [ 51 ], and anticancer drug [ 52 ] functions, but only for one or two fucoidan functions. In this experiment, we are the first person to integrate all fucoidan functions into one therapeutic system but are still affected by the instability of algal extracts.…”

Section: Discussionmentioning

confidence: 99%

Fucoidan with three functions extracted from Sargassum aquifolium integrated rice-husk synthesis dual-imaging mesoporous silica nanoparticle

Lee

Chen

et al. 2022

J Nanobiotechnol

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In this study, we used the nanoparticle delivery system to reduce the side effect of conventional cancer treatment- radiation therapy and chemotherapy. We used rice husk silicon source mesoporous silica nanoparticle doped in Eu3+ and Gd3+ as the carrier in the delivery system and to enable fluorescence and MRI dual-imaging functions for follow-up therapy. In addition, we choose a popular seaweed extract—fucoidan was extracted from the same brown algae—Sargassum aquifolium collected from Taiwan-Pingtung-Kenting-Chuanfan Rock. In this research, we used acid hydrolysis to prepared two different molecular weight fucoidan, the small molecular fucoidan (Fus) as drug, and the molecular weight approximately 1 kDa fucoidan (Ful) as the nanoparticle gatekeeper, and as targeting molecule for overexpressed P-selectin on the surface of the metastatic tumors. The results of the cell cytotoxicity experiment showed that HCT116 cancer cells have a survival rate of approximately 58.12% when treated with 200 μg/mL fucoidan. Dual-imaging rice husk mesoporous silica nanoparticles (rMSN-EuGd) were modified with 1 kDa fucoidan (Ful) as the gatekeeper and target, and the small molecule fucoidan (Fus) was loaded into nanoparticles (Ful-Fus@rMSN-EuGd) at a concentration of 200 μg/mL. The HCT116 cancer cells had a survival rate of approximately 55.56%. The cell cytotoxicity experiment results show that Ful-Fus@rMSN-EuGd can improve the anticancer effect of fucoidan, and the nanoparticle drug delivery system using fucoidan as a drug, target, and gatekeeper was successfully synthesized.

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Section: Discussionmentioning

confidence: 99%

Fucoidan with three functions extracted from Sargassum aquifolium integrated rice-husk synthesis dual-imaging mesoporous silica nanoparticle

Lee

Chen

et al. 2022

J Nanobiotechnol

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“…With K3-HBc NCs, CLT could been given by intravenous injection, making substantial progress in the future clinical application of CLT. In addition, many kidney-targeted drug delivery systems employ synthetic carriers, such as limposomes and micells, have been extensively investigated [43,44]. However the high cost, low purity, and variations remain the major obstacles to clinical translation.…”

Section: Discussionmentioning

confidence: 99%

Tubule-specific protein nanocages potentiate targeted renal fibrosis therapy

et al. 2021

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Background Despite the dramatic advances in modern medicine, efficient therapeutic measures for renal fibrosis remain limited. Celastrol (CLT) is effective in treating renal fibrosis in rat models, while causing severe systemic toxicity. Thus, we designed a tubule-specific nanocage (K3-HBc NCs) that effectively deliver CLT to tubular epithelial cell in a virus-like manner. The targeting ligand (K3) to tubular epithelial cells was displayed on the surface of Hepatitis B core protein (HBc) NCs by genetic fusion to the major immunodominant loop region. Ultra-small CLT nanodots were subtly encapsulated into the cavity through electrostatic interaction with the disassembly and reassembly of K3-HBc NCs, to yield K3-HBc/CLT complex. The efficacy of K3-HBc/CLT NCs were demonstrated in Unilateral ureteral obstruction (UUO)-induced renal fibrosis. Results The self-assembled K3-HBc/CLT could specifically target tubular epithelial cells via affinity with K3 ligand binding to the megalin receptor, significantly attenuating renal fibrosis. Remarkably, K3-HBc/CLT NCs significantly increased therapeutic efficacy and reduced the systemic toxicity in comparison with free CLT in UUO-induced mouse renal fibrosis model. Importantly, analysis of RNA sequencing data suggested that the anti-fibrotic effect of K3-HBc/CLT could be attributed to suppression of premature senescence in tubular epithelial cells via p21Cip1 and p16Ink4a pathway. Conclusion The tubule-specific K3-HBc/CLT represented a promising option to realize precise treatment for renal fibrosis.

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“…Produce pro-inflammatory cytokines/chemokines and interact with immune cells; 3. Apoptosis and necrosis; E-selectin Sialic acid [ 161 ] P-selectin Fucoidan [ 162 ] ICAM-1 ITGα L β 2 [ 151 ] Macrophages 1. Produce excess RONS; 2.…”

Section: Advantages Of Nanodrugs In Aki Treatmentmentioning

confidence: 99%