查找使用阿拉丁产品的科研文献

Biomimetic micelles to accurately regulate the inflammatory microenvironment for glomerulonephritis treatment

Huijuan Zhang,Qingqing He,Jingjing Wang,Yaping Wang,Xiangyang Xuan,Mingli Sui,Zhenzhong Zhang,Lin Hou

Glomerulonephritis is a key factor in leading to end-stage renal disease. Mesangial cell proliferation and macrophage infiltration are two prominent features linked in a vicious circle mechanism for glomerulonephritis progression. Herein, a novel biomimetic pH-sensitive nanomicelle (MM/HA-DXM) was constructed to synergize hyaluronic acid (HA)-activated macrophage phenotypic remodeling and dexamethasone (DXM)-mediated mesangial cell killing for precise treatment of glomerulonephritis. Owing to the camouflaged coating with endogenous macrophage membrane (MM), MM/HA-DXM could escape from RES phagocytosis and then be recruited to inflammatory glomerulus by active homing effect. Afterwards, HA-DXM nanomicelles ruptured in response to the weakly acidic glomerulonephritis microenvironment, to locally release HA and DXM . On the one hand, DXM can inhibit the abnormal proliferation of mesangial cells. On the other hand, HA transformed pro-inflammatory M1 macrophages into anti-inflammatory M2 phenotype to improve the glomerular inflammatory microenvironment. In doxorubicin-induced glomerulonephritis models, results revealed that MM/HA-DXM could specifically “homing” to inflammatory renal tissue with 4.33-fold improvement in targeting performance. In addition, in vivo pharmacodynamic results proved that after treatment with MM/HA-DXM, the proteinuria level decreased to 2.33 times, as compared with that of control group, demonstrating a superior therapeutic effect on glomerulonephritis via this collaborative two-pronged anti-inflammatory therapy strategy.

Nanocrystal-Loaded Micelles for the Enhanced In Vivo Circulation of Docetaxel

Meng Cheng,Qiaoming Liu,Tiantian Gan,Yuanying Fang,Pengfei Yue,Yongbing Sun,Yi Jin,Jianfang Feng,Liangxing Tu

Prolonging in vivo circulation has proved to be an efficient route for enhancing the therapeutic effect of rapidly metabolized drugs. In this study, we aimed to construct a nanocrystal-loaded micelles delivery system to enhance the blood circulation of docetaxel (DOC). We employed high-pressure homogenization to prepare docetaxel nanocrystals (DOC(Nc)), and then produced docetaxel nanocrystal-loaded micelles (DOC(Nc)@mPEG-PLA) by a thin-film hydration method. The particle sizes of optimized DOC(Nc), docetaxel micelles (DOC@mPEG-PLA), and DOC(Nc)@mPEG-PLA were 168.4, 36.3, and 72.5 nm, respectively. The crystallinity of docetaxel was decreased after transforming it into nanocrystals, and the crystalline state of docetaxel in micelles was amorphous. The constructed DOC(Nc)@mPEG-PLA showed good stability as its particle size showed no significant change in 7 days. Despite their rapid dissolution, docetaxel nanocrystals exhibited higher bioavailability. The micelles prolonged the retention time of docetaxel in the circulation system of rats, and DOC(Nc)@mPEG-PLA exhibited the highest retention time and bioavailability. These results reveal that constructing nanocrystal-loaded micelles may be a promising way to enhance the in vivo circulation and bioavailability of rapidly metabolized drugs such as docetaxel.Keywords:nanocrystals;micelles;circulation;in vivo;docetaxel

Novel active stealth micelles based on β2M achieved effective antitumor therapy

Jianwei Bao,Minxing Hu,Yuanmei Zhang,Qianqian Zhang,Feiyan Zhu,Qianli Zou,Jihui Tang

Micelles have been extensively investigated as drug delivery systems for loading of antitumor drugs with the advantages of good dispersibility, controllable size distribution, and high loading capacity. However, phagocytic clearance by the mononuclear phagocyte system remains a major impediment that inhibits blood circulation and thus tumor accumulation of micelles. Inspired by the antiphagocytic properties of β 2 -microglobulin (β 2 M), here we developed a β 2 M-derived peptide for the surface functionalization of micelles. A β 2 M-derived sequence was integrated with a matrix metalloproteinase-2 (MMP-2) cleavable sequence and then modified on the surface of poly(ethylene glycol)-b-poly(caprolactone) (PEG-PCL) micelles, endowing the micelles with both antiphagocytic and MMP-2-responsive properties. Compared to pristine PEG-PCL micelles, micelles modified with the dual-functional peptide exhibited higher inhibition of phagocytosis by macrophages in the absence of MMP-2, and enhanced internalization by tumor-associated macrophages in the presence of MMP-2, leading to enhanced tumor accumulation of the loaded photosensitizer, thus enabling antitumor therapy. These results demonstrated that antiphagocytic peptides derived from endogenous proteins are promising for functionalization of micelles in smart drug delivery.

Size Effect of Zwitterionic Peptide-Based Nanoscale Micelles on Cancer Therapy

Dandan Li,Xinyue Wei,Weili Xue,Liangbo Xu,Ziyin Xiang,Sihang Liu,Tian Yang,Shengfu Chen

Negative-charge-biased zwitterionic nanodrugs showed “stealthy” in blood circulation and “sticky” to sialic acid abundant tumor cells in the tumor microenvironment (TME), thereby prolonging blood circulation, increasing tumor targeting, and reducing accumulation in healthy liver and kidney. However, the correlation between the particle size, one of the crucial parameters of these nanodrugs, and their interactions with biological systems is unclear. Here, KEKDCDEKE (EK9) small peptide was used to replace zwitterionic polypeptides to prepare doxorubicin (DOX)-conjugated nanodrugs with well-controlled size, which is, respectively, 30, 60, and 90 nm diameter, for investigating the size effect on cancer therapy. Results showed that the size increase of these zwitterionic nanodrugs improves their blood circulation and retention in tumor but reduces the internalization rate and tumor tissue penetration, although all nanodrugs were self-assembled by the same conjugates. There is an optimal particle size, 60 nm in this work, for the zwitterionic nanodrugs to balance these effects, thereby improving their ability to inhibit tumor growth. These findings suggest that the particle size of zwitterionic nanodrugs also plays a particularly important role in controlling the behaviors of zwitterionic peptide-based nanodrugs.

Preparation of lignin-based carbon nanotubes using micelles as soft template

Cao Tu,Weihua Luo,Yuting Peng,Peng Yu,Chuangqi Shi,Zhiping Wu,Lishu Shao,Peng Zhan

As a natural renewable biomass resource with abundant reserves, lignin has broad prospects in the preparation of lignin-based carbon fibers and lignin-based carbon nanospheres . However, it remains a challenge to prepare carbon nanotubes using lignin as a carbon source. Herein, a feasible method for the preparation of lignin-based carbon nanotubes ( L -CNTs) using lignin as the carbon source based on mobile chemical vapor deposition is proposed. First, lignin-based micelles were used as a soft template to prepare a catalyst, and then L -CNTs were synthesized from gaseous products generated by lignin pyrolysis. The results reflected the important roles of the catalyst preparation process, the concentration of catalyst precursor, and the synthesis temperature on the morphologies and structures of the L -CNTs. By adjusting the reaction conditions, L -CNTs with diameters ranging from 10 to 110 nm and lengths ranging from 1 to 6 µm were obtained. The synthesized L -CNTs were mainly multi-walled carbon nanotubes, of which the crystal layer spacing was 0.35 nm, with a good graphitization degree and thermal stability. This synthesis strategy will provide a new method for the high-value utilization of lignin.

Nano-composite hydrogels of Cu-Apa micelles for anti-vasculogenic mimicry

Rui Kang,Mengdi Song,Zhou Fang,Kehai Liu

Vasculogenic mimicry (VM) describes the phenomenon whereby fluid-conducting vessels are formed by highly invasive tumour cells, which supply blood to tumours during their early growth stages. Single antiangiogenic agents have limited inhibitory effects on VM, therefore, a multi-pathway anti-VM strategy is required. In this study, Apatinib (Apa) was coordinated with Cu2+ to form a Cu-Apa copper complex. The latter was loaded into oligo-hyaluronic acid (HA) polymeric micelles (HA-Chol) and subsequently embedded in Astragalus polysaccharide-based in situ hydrogels (APsGels) to generate Cu-Apa/HA-Chol@APsGels. In this system, Cu-Apa exerts the combined effects of Cu2+ and Apa to inhibit VM; HA-Chol micelles achieve targeted drug delivery and enhance endocytosis efficiency; APsGels realise sustained release of the drugs to ensure an anti-VM effect. This system demonstrated improved VM inhibition with low cytotoxicity and high biocompatibility, wound healing, and transwell invasion in three-dimensional cell cultured VM. Moreover, this system significantly inhibited VM formation and melanoma growth in a mouse tumour transplantation model. This study provides an effective strategy for inhibiting VM.

Biofilm microenvironment-responsive polymeric CO releasing micelles for enhanced amikacin efficacy

Qian Zhou,Tengjiao Wang,Kunpeng Li,Shanyu Zhang,Kun Wang,Weilin Hong,Rongjun Liu,Peng Li

Biofilm-associated infections (BAI) have posed serious threats to public health. Novel therapy based on carbon monoxide (CO) is being increasingly appreciated. However, CO therapy like inhaled gas treatment was impeded owing to its low bioavailability. Besides, the direct use of CO releasing molecules (CORM) showed low therapeutic efficacy in BAI. Therefore, it is vital to improve the efficiency of CO therapy. Herein, we proposed polymeric CO releasing micelles (pCORM) from self-assembly of amphiphilic copolymers containing CORM bearing block as hydrophobic part and acryloylmorpholine block as hydrophilic part. The catechol modified CORM were conjugated through pH cleavable boronate ester bonds and releasing CO passively under biofilm microenvironment. When combined with subminimal inhibitory concentration antibiotic amikacin , pCORM could significantly enhance its bactericidal efficiency against biofilm-encapsulated multidrug-resistant bacteria, representing a promising approach to combat BAI.

Biotin-modified acid-sensitive micelles for enhancing antitumor effect of paclitaxel

Xinran Wang,Jieyi Pan,Haohui Shi,Na Liang,Shaoping Sun

This study was aimed at fabricating tumor targeting and acid-responsive micelles as carriers for paclitaxel (PTX). An amphipathic polymer TOS-Ace-PEG-Bio was designed and synthesized by conjugating α-tocopherol succinate (TOS) with biotinylated polyethylene glycol (PEG-Bio) via acetal bond. The polymer could self-assemble into nanosized micelles and encapsulate PTX. The PTX-loaded micelles possessed appropriate particle size with the mean value of 129.3 ± 0.9  nm . Strong pH dependent PTX release behavior was verified by in vitro drug release study. At cellular level, the PTX-loaded micelles could be selectively internalized by MCF-7 cells. The in vivo study also confirmed their excellent antitumor activity and reduced side effects. Based on these features, the TOS-Ace-PEG-Bio micelles were considered to be promising carriers for delivery of PTX.

Lotus-like nano-architectures constructed from self-assembled micelles via hierarchical assembly

Zhang Rongli,Fan Xiaoxia,Xu Xiaofang,Lv Jingjing,Jin Zhenzhen,Hao Hui,Zhang Cuige

Dopamine modified γ -polyglutamic acid ( γ -PGA-DA) copolymer and melamine (Mel) can self-assemble into Mel/ γ -PGA-DA micelles via weak intermolecular interactions in aqueous solution containing small amount of methanol. When Mel/ γ -PGA-DA micellar solution was cast on the surface of formvar stabilized with carbon support films, the lotus-like nano-architectures were formed on the surface of substrate via hierarchical assembly of micelles. The size of lotus-like nanoarchitectures was approximately 200 nm×500 nm. The possible driving forces for hierarchical assembly of micelles were the solution fluid and interaction between micelles. The hierarchical assembly of micelles was similar to the fractal aggregation of inorganic particles and a possible reason was discussed.

Fibronectin-targeted dual-acting micelles for combination therapy of metastatic breast cancer

Gong Zhuoran,Chen Min,Ren Qiushi,Yue Xiuli,Dai Zhifei

Stage IV breast cancer, which has a high risk of invasion, often develops into metastases in distant organs, especially in the lung, and this could threaten the lives of women. Thus, the development of more advanced therapeutics that can efficiently target metastatic foci is crucial. In this study, we built an dual-acting therapeutic strategy using micelles with high stability functionalized with fibronectin-targeting CREKA peptides encapsulating two slightly soluble chemotherapy agents in water, doxorubicin (D) and vinorelbine (V), which we termed C-DVM. We found that small C-DVM micelles could efficiently codeliver drugs into 4T1 cells and disrupt microtubule structures. C-DVM also exhibited a powerful ability to eradicate and inhibit invasion of 4T1 cells. Moreover, an in vivo pharmacokinetics study showed that C-DVM increased the drug circulation half-life and led to increased enrichment of drugs in lung metastatic foci after 24 h. Moreover, dual-acting C-DVM treatment led to 90% inhibition of metastatic foci development and reduced invasion of metastases. C-DVM could potentially be used as a targeted treatment for metastasis and represents a new approach with higher therapeutic efficacy than conventional chemotherapy for stage IV breast cancer that could be used in the future.

Self-Assembly of Antimicrobial Peptide-Based Micelles Breaks the Limitation of Trypsin

Weikang Yu,Yu Sun,Wenyu Li,Xu Guo,Xuesheng Liu,Wanpeng Wu,Wanqi Yu,Jiajun Wang,Anshan Shan

Targeting the limitation of antimicrobial peptides (AMPs) application in vivo, self-assembled AMPs library with specific nanostructures is expected to gradually overtake monomer AMPs libraries in the future. Peptide polymers are fascinating self-assembling nanoscale structures that have great advantage in biomedical applications because of their satisfactory biocompatibility and versatile properties. Herein, we describe a strategy for inducing the self-assembly of T9W into nanostructured antimicrobial micelles with evidently improved pharmacological properties, that is, PEGylation at the C-terminal of T9W (CT9W1000), an antibacterial biomaterial that self-assembles in aqueous media without exogenous excipients, has been developed. Compared with parental molecular, the CT9W1000 is more effective against Pseudomonas aeruginosa, and its antibacterial spectrum had also been broadened. Additionally, CT9W1000 micelles had higher stability under salt ion, serum, and acid–base environments. Importantly, the self-assembled structure is highly resistant to trypsin degradation, probably allowing T9W to be applied in clinical settings in the future. Mechanistically, by acting on membranes and through supplementary bactericidal mechanisms, CT9W1000 micelles contribute to the antibacterial process. Collectively, CT9W1000 micelles exhibited good biocompatibility in vitro and in vivo, resulting in highly effective treatment in a mouse acute lung injury model induced by P. aeruginosa PAO1 without drug resistance. These advances may profoundly accelerate the clinical transformation of T9W and promote the development of a combination of peptide-based antibiotics and PEGylated nanotechnology.

Uptake enhancement of curcumin encapsulated into phosphatidylcholine-shielding micelles by cancer cells

Lei Huang,Mengtan Cai,Xiaoxiong Xie,Yuanwei Chen,Xianglin Luo