JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2020
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IF 7.489
Gong Zhang,Liwei Zhang,Hengjun Rao,Yuefei Wang,Qing Li,Wei Qi,Xuejiao Yang,Rongxin Su,Zhimin He
We report the self-assembly of an ultra-pH-sensitive hydrogel from a simple dipeptide derivative, ferrocene-diphenylalanine (noted as Fc-FF). The pure Fc- L -Phe- L -Phe-OH (noted as (L)-Fc-FF) or Fc- D -Phe- D -Phe-OH (noted as (D)-Fc-FF) peptide could self-assemble into right- or left-handed nanohelices in a mixture of water and organic solvent leading to formation of stable chiral hydrogels at a very narrow pH range of 5.7–5.9. Intriguingly, if we used a racemic mixture (noted as (L,D)-Fc-FF) of (L)-Fc-FF and (D)-Fc-FF, stable hydrogels could only be formed at much lower pH values with a weak mechanical property. The results indicated that the molecular chirality has great influence on the gelation of the peptides. Moreover, we investigated the gelation behaviour of the peptides in various solvents. Here the water molecules are essential in directing the chiral self-assembly of Fc-FF into entangled chiral nanostructures, leading to the formation of stimuli-responsive hydrogels. And in the presence of water molecules, a small amount of organic co-solvents also has significant effect on the gelation of Fc-FF peptides. This work demonstrated that the gelation of such a bioorganometallic molecule is very sensitive to the molecular conformation of itself and the self-assembly environment (pH, solvents, etc.), which has potential applications in chemical sensing and biomedicine.
研究领域:
生物化学
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材料科学
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纳米技术
✓ 已验证
DOI
高影响因子
JOURNAL OF MATERIALS SCIENCE
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2019
·Vol. 54
·期 7
·5695-5711
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IF 3.442
Qin Jiejie,Huang Yan,Yan Guoqing,Wang Jun,Hu Liefeng,Zhang Panpan,Tang Rupei
In this work, the tumor-targeted ultra-pH-responsive conjugates (PBA/Dex-g-OE) and nontargeted conjugates (Dex-g-OE) were successfully prepared and could easily self-assemble into stable micelles with lower CMC values in neutral aqueous solution. Transmission electron microscopy and dynamic light scattering measurement indicated that the resulting micelles have desirable size distribution and regular spherical shape. The PBA/Dex-g-OE micelles possessed high stability in physiological condition and were pH sensitive to both extracellular and intracellular acidic conditions. Doxorubicin (DOX) was efficiently loaded to give the DOX-loaded micelles (PBA/Dex-g-OE-DOX and Dex-g-OE-DOX) with the desirable drug loading contents. In vitro cellular uptake and growth inhibition assays suggested that PBA/Dex-g-OE-DOX micelles were more efficiently internalized by monolayer tumor cells and three-dimensional multicellular tumor spheroids (MCTS) than nontargeted micelles (Dex-g-OE-DOX), leading to the fast and complete destruction of MCTS in vitro.
研究领域:
药剂学
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肿瘤学
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产品关联
DOI
高影响因子
ACS Nano
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2019
·
IF 13.903
Chao Kong,Yang Li,Zhengsheng Liu,Junxiao Ye,Zhaohui Wang,Ling Zhang,Weijian Kong,Huiqin Liu,Chun Liu,Huanhuan Pang,Zeping Hu,Jinming Gao,Feng Qian
Survival of KRAS mutant pancreatic cancer is critically dependent on reprogrammed metabolism including elevated macropinocytosis, autophagy, and lysosomal degradation of proteins. Lysosomal acidification is indispensable to protein catabolism, which makes it an exploitable metabolic target for KRAS mutant pancreatic cancer. Herein we investigated ultra-pH-sensitive micelles (UPSM) with pH-specific buffering of organelle pH and rapid drug release as a promising therapy against pancreatic cancer. UPSM undergo micelle–unimer phase transition at their apparent pKa, with dramatically increased buffer capacity in a narrow pH range (<0.3 pH). Cell studies including amino acid profiling showed that UPSM inhibited lysosomal catabolism more efficiently than conventional lysosomotropic agents (e.g., chloroquine) and induced cell apoptosis under starved condition. Moreover, pH-triggered rapid drug release from triptolide prodrug-loaded UPSM (T-UPSM) significantly enhanced cytotoxicity over non-pH-sensitive micelles (T-NPSM). Importantly, T-UPSM demonstrated superior safety and antitumor efficacy over triptolide and T-NPSM in KRAS mutant pancreatic cancer mouse models. Our findings suggest that the ultra-pH-sensitive nanoparticles are a promising therapeutic platform to treat KRAS mutant pancreatic cancer through simultaneous lysosomal pH buffering and rapid drug release.
研究领域:
肿瘤学
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药学
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癌症生物学
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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
Shuaijun Li,Caiting Meng,Qian Hao,Ruina Zhou,Luyao Dai,Yucheng Guo,Sitong Zhao,Xin Zhou,Chunju Lou,Ji Xu,Peng Xu,Jinfan Yang,Yifan Ding,Yanni Lv,Shengli Han,Shuai Li,Jing Li,Huafeng Kang,Zhengtao Xiao,Mingqian Tan,Xiaobin Ma,Hao Wu
Non-small cell lung cancer (NSCLC) brain metastases present a significant treatment challenge due to limited drug delivery efficiency and severe adverse reactions . In this study, we address these challenges by designing a “on/off” switchable crosslinked paclitaxel (PTX) nanocarrier , BPM-PD, with novel ultra-pH-sensitive linkages (pH 6.8 to 6.5). BPM-PD demonstrates a distinct “on/off” switchable release of the anti-cancer drug paclitaxel (PTX) in response to the acidic extratumoral microenvironment. The “off” state of BPM-PD@PTX effectively prevents premature drug release in the blood circulation, blood-brain barrier (BBB)/blood-tumor barrier (BTB), and normal brain tissue, surpassing the clinical PTX-nanoformulation (nab-PTX). Meanwhile, the “on” state facilitates precise delivery to NSCLC brain metastases cells. Compared to nab-PTX, BPM-PD@PTX demonstrates improved therapeutic efficacy with a reduced tumor area (only 14.6%) and extended survival duration, while mitigating adverse reactions (over 83.7%) in aspartate aminotransferase (AST) and alanine aminotransferase (ALT), offering a promising approach for the treatment of NSCLC brain metastases. The precise molecular switch also helped to increase the PTX maximum tolerated dose from 25 mg/kg to 45 mg/kg This research contributes to the field of cancer therapeutics and has significant implications for improving the clinical outcomes of NSCLC patients.
研究领域:
肿瘤学
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药学
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纳米技术
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癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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