CHEMICAL ENGINEERING JOURNAL
·
2017
·
IF 6.216
Na Wen,Shaoyu Lü,Chunmei Gao,Xiubin Xu,Xiao Bai,Can Wu,Piao Ning,Mingzhu Liu
Both blood stability and glucose responsiveness for carriers are the most important issues in insulin controlled release studies. However, few reports focus on reducing macrophage response performance for drug carriers themselves. Zwitterionic self-assembled micelles mitigated recognition by immune cell has evolved to address this limitation. In this work, novel zwitterionic dialdehyde starch-based micelles, sulfobetaine (SB) as the hydrophilic shell, and 3-aminophenylboronic acid (APBA) as glucose-responsive groups to the dialdehyde starch (DAS) backbones (SB-DAS-APBA) with glucose-responsive behavior were developed. Insulin release from the nanocarriers is sensitive to the different concentration of the glucose, rapidly at the condition of 3 mg/mL of glucose at pH 7.4. Methyl thiazolyl tetrazoliumviability (MTT) assay confirmed that zwitterion micelles were cytobiocompatible and low cytotoxic activity with A549 cells. For comparison, PEGylation micelles, monomethyl ether (mPEG) as the hydrophilic shell, and APBA as glucose-responsive groups to the DAS backbones (mPEG-DAS-APBA), were also synthesized. Confocal laser scanning microscopy (CLSM) and flow cytometry results displayed that PEGylation and zwitterion coating micelles have different recognition processes in contact with macrophages. After 4 h, doxorubicin (Dox) fluorescence of the Dox-loaded mPEG-DAS-APBA micelle groups were mostly located in nuclei. However, SB-DAS-APBA micelle groups were slightly detected in both nuclei and cytosol. In addition, the fluorescence signals of mPEG-DAS-APBA micelles showed enhanced trend than that of SB-DAS-APBA micelles in macrophage cells. These results suggest that, as drug carriers, zwitterionic self-assembled micelles SB-DAS-APBA not only possessed glucose-responsive insulin delivery property, but also reduced macrophage response performance.
研究领域:
药学
·
生物材料
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2022
·
IF 7.419
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.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2020
·Vol. 16
·期 46
·2004240
·
IF 11.459
Ya-Ru Zhang,Jia-Qi Luo,Jing-Yang Zhang,Wei-Min Miao,Jia-Si Wu,Hua Huang,Qi-Song Tong,Song Shen,Kam W. Leong,Jin-Zhi Du,Jun Wang
Activation of the phagocytosis of macrophages to tumor cells is an attractive strategy for cancer immunotherapy, but the effectiveness is limited by the fact that many tumor cells express an increased level of anti-phagocytic signals (e.g., CD47 molecules) on their surface. To promote phagocytosis of macrophages, a pro-phagocytic nanoparticle (SNPA CALR&aCD47 ) that concurrently carries CD47 antibody (aCD47) and a pro-phagocytic molecule calreticulin (CALR) is constructed to simultaneously modulate the phagocytic signals of macrophages. SNPA CALR&aCD47 can achieve targeted delivery to tumor cells by specifically binding to the cell-surface CD47 and block the CD47-SIRPα pathway to inhibit the “don't eat me” signal. Tumor cell-targeted delivery increases the exposure of recombinant CALR on the cell surface and stimulates an “eat me” signal. Simultaneous modulation of the two signals enhances the phagocytosis of 4T1 tumor cells by macrophages, which leads to significantly improved anti-tumor efficacy in vivo. The findings demonstrate that the concurrent blockade of anti-phagocytic signals and activation of pro-phagocytic signals can be effective in macrophage-mediated cancer immunotherapy.
研究领域:
癌症免疫学
·
纳米技术
·
免疫疗法
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2022
·
IF 8.039
Wen Song,Fan Yang,Hang Yang,Yi Xu,Shu-Jun Song,Yan Meng,Si-Tian Wei,Tao Wan,Ying Zhou,Bin Zhou,Jing Kuang,Tao Yu,Wen-Xiu Qiu
Compared to the activation of acquired immunity by the immune checkpoint blockade, the activation of innate immunity via anti-phagocytosis checkpoint blockade could significantly increase the beneficiary population of immunotherapy. However, the activation of innate immunity and the occurrence of phagocytosis are only accomplished when the interaction between pro-phagocytosis signals and anti-phagocytosis signals is realized. Herein, a versatile nanoplatform (DHMR) based on mesoporous silicon nanoparticles (MSNPs) has been constructed. Two drugs, doxorubicin, a chemotherapeutic drug which could initiate tumor cells to release pro-phagocytosis signals, and RRx-001, an immunoadjuvant that could effectively implement the anti-phagocytosis checkpoint blockade, were loaded in MSNPs. Further decoration of hyaluronic acid encapsulation endows DHMR with the function of tumor targeting and long circulation. Ultimately, the DHMR system could efficiently and accurately target tumor tissue, release the drugs in the tumor microenvironment, achieve the activation of innate immunity, and finally dramatically inhibit the growth and metastasis of tumor cells.
研究领域:
肿瘤学
·
免疫疗法
·
纳米技术
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2018
·
IF 8.806
Zhenqi Jiang,Yuchen Tian,Dingying Shan,Yinjie Wang,Ethan Gerhard,Jianbi Xia,Rong Huang,Yan He,Aiguo Li,Jianchao Tang,Huimin Ruan,Yong Li,Juan Li,Jian Yang,Aiguo Wu
Nanoparticle-based tumor therapies are extensively studied; however, few are capable of improving patient survival time due to premature drug leakage, off target effects, and poor tissue penetration. Previously, we successfully synthesized a novel family of Y 1 receptor (Y 1 R) ligand modified, photoluminescent BPLP nanobubbles and nanoparticles for targeted breast cancer ultrasound imaging ; however, increased accumulation could also be observed in the liver, kidney, and spleen, suggesting significant interaction of the particles with macrophages in vivo . Herein, for the first time, we imparted antiphagocytosis capability to Y 1 R ligand functionalized BPLP-WPU polymeric micelles through the incorporation of a CD47 human glycoprotein based self-peptide. Application of self-peptide modified, DOX loaded micelles in vivo resulted in a 100% survival rate and complete tumor necrosis over 100 days of treatment. In vivo imaging of SPION loaded, self-peptide modified micelles revealed effective targeting to the tumor site while analysis of iron content demonstrated reduced particle accumulation in the liver and kidney, demonstrating reduced macrophage interaction, as well as a 2-fold increase of particles in the tumor. As these results demonstrate, Y 1 R ligand, self-peptide modified BPLP-WPU micelles are capable of target specific cancer treatment and imaging, making them ideal candidates to improve survival rate and tumor reduction clinically.
研究领域:
癌症治疗
·
纳米医学
·
药理学
·
分子影像
·
生物医学工程
✓ 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）