JOURNAL OF NANOPARTICLE RESEARCH
·
2017
·Vol. 19
·期 12
·1-11
·
IF 2.02
Chen Daquan,Song Xiaoyan,Wang Kaili,Guo Chunjing,Yu Yueming,Fan Huaying,Zhao Feng
In this article, in order to enhance the bioavailiability and tumor targeting of curcumin (Cur), the oligosaccharides of hyaluronan conjugates, folic acid-oligosaccharides of hyaluronan-acetal-menthone 1,2-glycerol ketal (FA-oHA-Ace-MGK) carried oHA as a ligand to CD44 receptor, double-pH-sensitive Ace-MGK as hydrophobic moieties, and FA as the target of folate receptor. The structure characteristics of this smart response multifunctional dual-targeting nano-sized carrier was measured by fourier-transform infrared (FT-IR) and nuclear magnetic resonance ( 1 H–NMR). Cur, an anticancer drug, was successfully loaded in FA-oHA-Ace-MGK micelles by self-assembly. The measurement results of transmission electron microscopy (TEM) presented that the Cur-loaded micelles were spherical in shape with the average size of 166.3 ± 2.12 nm and zeta potential − 30.07 mV. Much more encapsulated Cur could be released at mildly acidic environments than at pH 7.4, from the Cur-FA-oHA-Ace-MGK micelles. Cytotoxicity assay indicated that non-Cur loaded micelles mostly had no cytotoxicity to MCF-7 cells and A549 cells, and Cur-loaded micelles had significantly lower survival rate than Cur suspension in the same concentration, which proved that the drug-loaded micelles can effectively inhibit tumor cell growth. The targeting of CD44 receptors and folate receptors was proved in vitro cellular uptake assay. These results showed the promising potential of FA-oHA-Ace-MGK as an effective nano-sized carrier for anti-tumor drug delivery.
研究领域:
药学
·
肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF NANOPARTICLE RESEARCH
·
2015
·Vol. 17
·期 10
·1-10
·
IF 2.184
Chen Daquan,Wang Guohua,Song Weiguo,Zhang Qiang
Most anticancer drugs cannot kill cancer stem cells (CSCs) effectively, which lead to the failure of anticancer chemotherapy, such as relapse and metastasis. In this study, we prepared a multifunctional oligosaccharides of hyaluronan (oHA) conjugates, oHA-histidine-menthone 1,2-glycerol ketal (oHM). The oHM conjugates possess pH-sensitive menthone 1,2-glycerol ketal (MGK) as hydrophobic moieties and oHA as the target of CD44 receptor. Anticancer drugs, curcumin(Cur) and paclitaxel(PTX), were loaded into oHM micelles via self-assembly. Then, oHM micelles were mineralized through controlled deposition of inorganic calcium and phosphate ions on the nanoparticular shell via a sequential addition method to fabricate the “nano-eggs.” The formed nano-eggs had a smaller size (120.6 ± 4.5 nm) than oHM micelles (158.6 ± 6.4 nm), indicating that mineralization made the appearance of compact nanoparticles. Interestingly, when the nano-eggs were put into the acidic conditions (pH 6.5), their outer shell(inorganic minerals) will be destroyed with the larger size, while the “nano-eggs” were stable under pH 7.4. For both nano-eggs and oHM micelles, the Cur and PTX were released in a sustained manner depending on the pH of the solution. However, the nano-eggs showed much lower released than the oHM micelles due to the dissolution of the inorganic minerals and pH-sensitive ketal at mildly acidic environments (pH 6.5). In vivo study, the nano-eggs could get to the tumor site more effectively than oHM micelles. CSCs were sorted by a side population assay from MDA-MB-231 breast cancer cell lines over-expressing CD44 receptors. Antitumor activity was also evaluated on MDA-MB-231 xenografts in nude mice. The antitumor efficacy indicated that nano-eggs with co-delivery of Cur and PTX produced the strongest antitumor efficacy, and nano-eggs showed strong activity against cancer stem cells. These double pH-sensitive nano-eggs may provide a promising strategy for drug delivery to both cancer cells and cancer stem cells.
研究领域:
药学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2021
·
IF 6.953
Tao Liao,Chang Liu,Jun Ren,Hui Chen,Ying Kuang,Bingbing Jiang,Jianli Chen,Zhengguang Sun,Cao Li
To enhance drug utilization and reduce their side effects, the strategy of “tumor-triggered targeting” was introduced to fabricate dual-pH-sensitive chitosan (CHI)/mesoporous silica nanoparticle (MSN)-based anticancer drug delivery system (DDS) in this work. Model drug doxorubicin hydrochloride (DOX) was loaded in MSN, which was modified with benzimidazole (Bz) group. Then chitosan- graft - β -cyclodextrin (CHI- g -CD) was applied as the “gatekeeper” to cover MSN through host-guest interaction between β -CD and Bz. After being coated with targeting peptide adamantane-glycine-arginine-glycine-aspartic acid-serine (Ad-GRGDS), methoxy poly(ethylene glycol) benzaldehyde (mPEG-CHO) was finally grafted on CHI through the pH-sensitive benzoic imine bond. Due to the dynamic protection of PEG, the obtained carriers were “stealthy” at pH 7.4, but could reveal the shielded targeting peptide and the positive charge of CHI in the weakly acidic environment achieved a “tumor-triggered targeting”. Inside cancer cells, the interaction between β -CD and Bz group could be destroyed due to the lower pH, resulted in DOX release. Both in vitro and in vivo studies proved the DDS could targeting induce cancer cell apoptosis, inhibit tumor growth, and reduce the cytotoxicity of DOX against normal cells. It is expected that the system named DOX@MSN-CHI-RGD-PEG could be a potential choice for cancer therapy.
研究领域:
生物医学工程
·
药学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2015
·Vol. 11
·期 21
·2543-2554
·
IF 8.368
Shi-Song Han,Ze-Yong Li,Jing-Yi Zhu,Kai Han,Zheng-Yang Zeng,Wei Hong,Wen-Xin Li,Hui-Zhen Jia,Yun Liu,Ren-Xi Zhuo,Xian-Zheng Zhang
A novel dual-pH sensitive charge-reversal strategy is designed to deliver antitumor drugs targeting to tumor cells and to further promote the nuclei internalization by a stepwise response to the mildly acidic extracellular pH (≈6.5) of a tumor and endo/lysosome pH (≈5.0). Poly( l -lysine)- block –poly( l -leucine) diblock copolymer is synthesized and the lysine amino residues are amidated by 2,3-dimethylmaleic anhydride to form β-carboxylic amide, making the polypeptides self-assemble into negatively charged micelles. The amide can be hydrolyzed when exposed to the mildly acidic tumor extracellular environment, which makes the micelles switch to positively charged and they are then readily internalized by tumor cells. A nuclear targeting Tat peptide is further conjugated to the polypeptide via a click reaction. The Tat is amidated by succinyl chloride to mask its positive charge and cell-penetrating function and thus to inhibit nonspecific cellular uptake. After the nanoparticles are internalized into the more acidic intracellular endo/lysosomes, the Tat succinyl amide is hydrolyzed to reactivate the Tat nuclear targeting function, promoting nanoparticle delivery into cell nuclei. This polypeptide nanocarrier facilitates tumor targeting and nuclear delivery simultaneously by simply modifying the lysine amino residues of polylysine and Tat into two different pH-sensitive β-carboxylic amides.
研究领域:
药学
·
纳米技术
·
癌症治疗
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INORGANIC CHEMISTRY COMMUNICATIONS
·
2022
·
IF 3.428
Hao Guo,Songjie Fan,Jianhua Liu,Yumei Wang
The synergistic effect of leucovorin calcium (LVCa) on 5-fluorouracil (5-FU) has been widely confirmed, but as far as we know, there is no effective way to simultaneously deliver LVCa and 5-FU to tumor sites. In this paper we innovatively established a dual-pH sensitive drug release system based on ZIF-8 frameworks decorated with hyaluronic acid-LVCa bioconjugates linked with an acid-cleavable hydrazone bond to achieve the combinatorial delivery and on-demand drug release of 5-fluorouracil (5-FU) and leucovorin calcium (LVCa) at the acidic pH conditions of the tumor sites. The as-obtained HA-LVCa/5-FU@ZIF-8 nanoplatforms load 0.35 g of 5-FU and 0.048 g of LVCa per gram and exhibited high inhibiting colon cells growth performance in vitro.
研究领域:
药学
·
癌症治疗
·
纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
Science Advances
·
2020
·Vol. 6
·期 6
·
IF 13.117
Zecong Xiao,Zhenwei Su,Shisong Han,Jinsheng Huang,Liteng Lin,Xintao Shuai
The response to programmed cell death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) blockade in cancer immunotherapy is limited because of multiple immune evasion mechanisms. Here, a previously unknown strategy is proposed to synergize the nuclear factor κB (NF-κB) inhibition and PD-1 blockade for antitumor immunotherapy. A dual pH-sensitive nanocarrier loading curcumin (CUR) and anti–PD-1 monoclonal antibody (aPD-1) may bind to circulating PD-1+ T cells and then follow their infiltration into the tumor. Furthermore, the nanodrug bound to PD-1+ T cells may be released in the tumor microenvironment, leaving aPD-1 to block PD-1 on T cells and generating a CUR-encapsulated cationic nanodrug that can be easily taken up by tumor cells/tumor associated macrophages (TAMs). Thus, not only the antitumor T cells mediate efficient CUR delivery to tumor but also the efficient CUR delivery promotes the tumor infiltration of antitumor T cells, thereby resulting in effective activation of antitumor immunity.
研究领域:
癌症免疫疗法
·
纳米技术
·
免疫学
·
药理学
✓ 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）