INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
·
IF 4.845
Liqiong Zha,Jiajia Qian,Beilei Wang,Huanhuan Liu,Caiyun Zhang,Qiannian Dong,Weidong Chen,Lufeng Hong
As one of the active pharmaceutical ingredients in Gamboge, Gambogenic acid (GNA) has shown diverse anti-tumor activities. To reduce the vascular irritation of GNA and improve its water solubility, tumor targeting, and bioavailability, GNA loaded Zein nanoparticles ( [email protected] NPs) was further coated by polydopamine (PDA) to develop [email protected] NPs by anti-solvent precipitation and surface modification. The results showed that particle size and Zeta potential of [email protected] NPs were about 310 nm and −40.8 mV with core–shell morphology confirmed by TEM. [email protected] NPs increased the water solubility of GNA by more than 700 times and showed pH-sensitive release behavior in PBS with pH 6.86. In vitro cytotoxicity tests showed that [email protected] NPs had higher inhibitory activity on HepG2 cells than free GNA, and their IC 50 were 1.59 μg/mL and 9.89 μg/mL, respectively. Additionally, the hemolysis and vascular irritation assay showed that [email protected] NPs had good cytocompatibility and reduced the irritation of GNA to blood vessels. Moreover, the in vivo pharmacokinetic experiments exhibited that the C max and AUC 0-t of [email protected] NPs were significantly improved approximately by 2.09-fold and 3.48-fold over that of GNA, respectively. In conclusion, [email protected] NPs solve many defects of GNA and provide a tumor-targeting drug delivery for GNA.
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高影响因子
Chemosensors
·
2023
·Vol. 11
·期 8
·425
·
IF 4.2
Jiani Li,Fanfan Liang,Li Han,Xiaoxuan Yu,Dingbin Liu,Wensheng Cai,Xueguang Shao
Accurate determination of extra-cellular pH (pHe) and intra-cellular pH (pHi) is important to cancer diagnosis and treatment because tumor cells exhibit a lower pHe and a slightly higher pHi than normal cells. In this work, the characteristic absorption of water in the near-infrared (NIR) region was utilized for the determination of pHe and pHi. Dulbecco’s modified eagle medium (DMEM) and bis (2-ethylhexyl) succinate sodium sulfonate reverse micelles (RM) were employed to simulate the extra- and intra-cellular fluids, respectively. Continuous wavelet transform (CWT) was used to enhance the resolution of the spectra. Quantitative models for pHe and pHi were established using partial least squares (PLS) regression, producing relative errors of validation samples in a range of −0.74–2.07% and −1.40–0.83%, respectively. Variable selection was performed, and the correspondence between the selected wavenumbers and water structures was obtained. Therefore, water with different hydrogen bonds may serve as a good probe to sense pH within biological systems.Keywords:near-infrared spectroscopy;water structure;extra-cellular pH;intra-cellular pH;partial least squares regression
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高影响因子
JOURNAL OF MATERIALS SCIENCE
·
2018
·Vol. 53
·期 15
·10653-10665
·
IF 2.993
Chen Hui,Kuang Ying,Liu Rong,Chen Zhongyin,Jiang Bingbing,Sun Zhengguang,Chen Xueqin,Li Cao
Reducing the side effects and improving the drug utilization are important work in anti-cancer drug delivery. In this paper, a novel dual-pH-sensitive drug delivery system was reported. Mesoporous silica nanoparticle (MSN) was applied to load anti-cancer drug doxorubicin hydrochloride (DOX) and was covered by mono-6-deoxy-6-EDA- β -cyclodextrine ( β -CD-NH 2 ) to block the pores through pH-sensitive boronate ester bond. And the carriers were then coated with methoxy poly(ethylene glycol) (mPEG) through another pH-sensitive benzoic imine bond. mPEG leaving studies, in vitro cellular uptake studies and the flow cytometry analysis, proved that carriers was “stealthy” at pH 7.4, but could be “activated” for cytophagy by cancer cells in weakly acidic tumor tissues (pH 6.5) due to the departure of mPEG. β -CD-NH 2 leaving studies, the in vitro drug release studies and the in vitro cytotoxicity studies proved that boronate ester bond linking MSN and β -CD-NH 2 was stable at both pH 7.4 and 6.5, but could be hydrolyzed intracellular to release DOX for cellular apoptosis due to the lower pH (5.0). In summary, the novel dual-pH-sensitive drug delivery system fabricated with a dynamic protection strategy should have great application potential in anti-cancer drug delivery fields.
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高影响因子
LANGMUIR
·
2021
·
IF 3.882
Yimin Zhou,Cong Chang,Zuhao Liu,Qiuling Zhao,Qingni Xu,Chaohua Li,Yuqi Chen,Yueli Zhang,Bo Lu
Hollow mesoporous silica nanoparticles (HMSNs) served as nanocarriers for transporting doxorubicin hydrochloride (DOX) and indocyanine green (ICG) and were incorporated into a pH-sensitive targeted drug delivery system (DDS). Boronate ester bonds were employed to link HMSNs and dopamine-modified hyaluronic acid (DA-HA), which acted as both the “gatekeeper” and targeting agents (HMSNs-B-HA). Well-dispersed HMSNs-B-HA with a diameter of about 170 nm was successfully constructed. The conclusion was drawn from the in vitro drug release experiment that ICG and DOX (ID) co-loaded nanoparticles (ID@HMSNs-B-HA) with high drug loading efficiency could sustain drug release under acidic conditions. More importantly, in vitro cell experiments perfectly showed that ID@HMSNs-B-HA could well inhibit murine mammary carcinoma (4T1) cells via chemotherapy combined with photodynamic therapy and accurately target 4 T1 cells. In summary, all test results sufficiently demonstrated that the prepared ID@HMSNs-B-HA was a promising nano-DDS for cancer photodynamic combined with chemotherapy.
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高影响因子
POLYMER
·
2020
·
IF 4.231
Kun Yu,Xiyao Yang,Lihua He,Rong Zheng,Jie Min,Hongying Su,Shaoyun Shan,Qingming Jia
Dual and multi-stimuli responsive polymeric nanoparticles that can respond to two or more signals have been demonstrated as prospective drug carriers with enhanced tumor accumulation and on-demand drug release profiles. In this study, dextran-based (Dex-SS) nanogels were developed via a facile method based on the disulfide containing Schiff base formation between polyaldehyde dextran and cystamine in water-in-oil inverse microemulsion . Acidic and reductive (GSH) environment sensitive degradation behaviors of the resulted nanogels were investigated by morphology analysis of the treated nanogels using SEM imaging. Doxorubicin (DOX) was covalently conjugated into the dextran nanogels via Schiff base linkages, and pH/GSH dual sensitive drug release profiles were demonstrated. Effective cell uptake of the DOX-loaded nanogels was finally identified by human cancer cell line of H1299. Take advantage of the acidic and reductive tumor microenvironment, the dual-stimuli responsive Dex-SS nanogels can serve as microenvironment-sensitive drug delivery systems for tumor therapy.
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高影响因子
INDUSTRIAL CROPS AND PRODUCTS
·
2022
·
IF 6.449
Conghua Yi,Qinghe Xu,Dongjie Yang,Miao Wang
In this work, we developed a novel technique to prepare pH-responsive charge reversal nanospheres based on softwood kraft lignin (SKL) through two steps modification and high efficient self-assembly. SKL was first grafted with imidazole groups by Mannich reaction and further fabricated into acetylated histidine-modified lignin (Ace-SKL-HIS) via acetylation reaction. Ace-SKL-HIS nanospheres (Ace-SKL-HIS NPs) were prepared by fast vacuum evaporation method, their effective diameters (ED) were around 100 nm, exhibited low Polydispersity Index(PDI, <0.2) and good shape. Ace-SKL-HIS NPs demostrated excellent pH response performance with charge reversal under acidic environment. Then, curcumin was applied as a model drug to prepare drug-loaded nanospheres ( [email protected] ). The drug loading degree (DL%) and encapsulation efficiency (EE%) were 22.34 % and 70.76 %, respectively. The in vitro release behavior of curcumin exhibited excellent pH dependent release property, 76.82 % release at pH 5.7 while only 12.92 % at pH 7.4 in 120 h. Furthermore, in vitro cytotoxicity studies showed that [email protected] had potent anti-tumor effect, with IC 50 of 28.16 μg/ mL. This study constructed a promising nanocarrier platform for cancer drug delivery, which paved a new way to the high value-added application of lignin.
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高影响因子
RSC Advances
·
2022
·Vol. 12
·期 35
·22748-22759
·
IF 4.036
Tao Zhang,Xiao-Qiao Hong,Hai-Tao Zhi,Jinhui Hu,Wen-Hua Chen
Lysosomal pH is an important modulator for many cellular processes. An agent that is capable of regulating lysosomal pH may find a wide range of potential applications in the field of biomedicine. In this study, we describe the synthesis of a family of morpholinyl-bearing arylsquaramides as small-molecule lysosomal pH modulators. These compounds are able to efficiently facilitate the transmembrane transport of chloride anions as mobile carriers across vesicular and cellular phospholipid membranes. They are capable of specifically alkalizing liposomes, disrupting the homeostasis of lysosomal pH and inactivivating lysosomal Cathepsin B enzyme. Anion transport is considered as the probable mechanism of action for the high efficiency of these compounds to modulate lysosomal pH. The present findings present a novel means to efficiently regulate lysosomal pH, which is in contrast to the methods shown by conventional lysosomal pH modulators that generally function by either acting as a weak base/acid, or releasing a basic/acidic component in lysosomal environments to change lysosomal pH.
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高影响因子
CHINESE JOURNAL OF POLYMER SCIENCE
·
2019
·Vol. 37
·期 12
·1224-1233
·
IF 2.804
Gong Heng-Ye,Chen Yan-Gui,Yu Xing-Su,Xiao Hong,Xiao Jin-Peng,Wang Yong,Shuai Xin-Tao
Drug-resistance and drastic side effects are two major issues of traditional chemotherapy which may result in trail failure even death. Nanoparticle-mediated multidrug combination treatment has been proven to be a feasible strategy to overcome these challenges. In the present study, amphipathic block polymer of methoxyl poly(ethylene glycol)-poly(aspartyl(dibutylethylenediamine)- co -phenylalanine) (mPEG-P(Asp(DBA)- co -Phe)) was synthesized and self-assembled into pH-responsive polymeric vesicle. The vesicle was utilized to co-deliver cancer-associated epidermal growth factor (EGFR) inhibitor of afatinib and DNA-damaging chemotherapeutic doxorubicin hydrochloride (DOX) for enhanced non-small-cell lung cancer (NSCLC) therapy. As evaluated in vitro , the pH-responsive design of nanovesicle resulted in a rapid release of encapsulated drugs into tumor cells and caused enhanced cell apoptosis. In addition, in vivo therapeutic studies were conducted and the results evidenced that the co-delevery of DOX and afatinib using pH-sensitive nanovector was a promising strategy for NSCLC treatment.
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高影响因子
Acta Biomaterialia
·
2021
·
IF 8.947
Dongsheng Yu,Yazhou Wang,Jifeng Chen,Shuang Liu,Shaohui Deng,Chengbo Liu,Iain McCulloch,Wan Yue,Du Cheng
Semiconducting polymer (SP) is a promising photothermal agent in the antitumor application, but the co-delivery of the second near-infrared window (NIR-II)-based SPs with chemotherapeutic drug (e.g., doxorubicin (DOX)) remains a challenge. Here, SPs were firstly improved via backbone and alkyl side-chain engineering, and afterward, SPs and pH-sensitive prodrug copolymer self-assembled into a nanoparticle for a photoacoustic (PA)-imaging guided combination of photothermal therapy and chemotherapy. SP-encapsulated nanoparticles exhibited a high photothermal conversion efficiency of 45% at a relatively low power level of NIR irradiation (0.3 W/cm 2 for 5 min). DOX was rapidly released in response to the acidic lysosomal environment. PA and fluorescence imaging confirmed that the photothermal therapy effectively drove DOX penetration inside tumor tissue, and it resulted in the killing of the surviving tumor cells from hyperthermia. The synergistic effect of SP-based photothermal therapy and DOX-induced chemotherapy was verified in vivo . Overall, the co-delivery of the SP and DOX using pH-sensitive nanoparticles represents a feasible strategy for photothermal therapy with potentially synergistic drug effects. Statement of significance Recent years have yielded great progress in semiconducting polymers (SPs)-based photothermal therapy for anticancer treatment. However, studies about molecular weight and side-chain of SPs on photothermal conversion efficiency are limited, and investigation of controlled codelivery with chemotherapeutic drug is lacking. Here, we improved the SPs performance via backbone and side-chain engineering, and afterward offered a pH-sensitive DOX-conjugated amphiphilic copolymer to encapsulate SPs. SP-encapsulated nanoparticles exhibited high photothermal conversion efficiency at a clinically feasible power level of NIR irradiation. NIR irradiation-generated hyperthermia not only killed tumor cells but also promoted DOX penetration inside the tumor tissue to ablate the tumor cells that survived hyperthermia. The synergistic effect of SP-based photothermal therapy and DOX-induced chemotherapy was verified in vivo .
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高影响因子
BIOMATERIALS
·
2017
·
IF 8.402
Yanan Tan,Yun Zhu,Yue Zhao,Lijuan Wen,Tingting Meng,Xuan Liu,Xiqin Yang,Suhuan Dai,Hong Yuan,Fuqiang Hu
Mitochondria, crucial regulators of inducing tumor cells apoptosis, can be treated as the prime target for tumor therapy. The selective and responsive release of proapoptotic therapeutics into mitochondria may notably improve antitumor efficiency. Herein, (4-Carboxybutyl) triphenylphosphonium bromide (CTPP), a lipophilic cation, was conjugated with glucolipid-like conjugates (CSOSA) to produce mitochondria-targeted conjugates (CTPP-CSOSA). Loading with weakly acidic drug Celastrol (Cela), CTPP-CSOSA/Cela micelles could selectively respond to mitochondrial alkaline pH (pH 8.0), controlled by the weaker interaction between hydrophobic core of micelles and Cela with higher solubility at pH 8.0. However, there was a slow drug release behavior at pH 7.4 and pH 5.0. It illustrated that CTPP-CSOSA/Cela could realize mitochondrial fast drug release, and decrease drug leakage in the cytoplasm and lysosome . CTPP-CSOSA/Cela highly enhanced ROS levels, which further induced mitochondria membrane potential decreasing and more Cytochrome C releasing into cytoplasm, then promoted tumor cells apoptosis notably. In vivo , CTPP-CSOSA had an enhanced accumulation in tumor tissue, compared with CSOSA. Moreover, the tumor-inhibition rate of CTPP-CSOSA/Cela was 80.17%, which was significantly higher than CSOSA/Cela (58.35%) and Cela (54.89%). Thus, CTPP-CSOSA/Cela micelles with mitochondrial targeting and alkaline pH-responsive release capability could provide a new strategy for tumor therapy.
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高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2019
·
IF 4.959
Weijun Xu,Jinlei Wang,Junmin Qian,Guanghui Hou,Yaping Wang,Lijie Ji,Aili Suo
Combination of different therapy modalities with multiple tumoricidal mechanisms has emerged as a promising anticancer strategy. Herein, we reported an aldehyde/catechol-functionalized hyaluronic acid (DAHA) and hydroxyethyl chitosan (HECS) decorated gold nanorod (GNR) platform for combined chemo-photothermal therapy of breast cancer. The DAHA was synthesized by conjugating dopamine onto oxidized hyaluronic acid. The nanoplatform was prepared by successively modifying GNR with DAHA via Au-catechol bonds, conjugating DOX onto DAHA moiety through Schiff base linkage, and coating HECS interlayer for charge-reversal and hyaluronic acid corona for tumor cell targeting. The resulting nanoplatform GNR-HA DOX CH exhibited acid-triggered surface charge-reversal and pH/NIR dual-responsive drug release behaviors. The nanoplatform could be efficiently internalized into MCF-7 breast cancer cells and displayed greater cancer cell killing than individual modalities. Therefore, polysaccharide decoration could ensure the co-delivery of GNR and DOX into cancer cells, and the developed GNR-HA DOX CH holds great potential for breast cancer treatment.
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高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Xiangshi Sun,Kongtong Yu,Yulin Zhou,Shiyan Dong,Wenji Hu,Yating Sun,Yuhuan Li,Jing Xie,Robert J. Lee,Fengying Sun,Yifan Ma,Shengnian Wang,Betty Y. S. Kim,Yifan Wang,Zhaogang Yang,Wen Jiang,Youxin Li,Lesheng Teng
The use of superoxide dismutase (SOD) is currently limited by its short half-life, rapid plasma clearance rate, and instability. We synthesized a small library of biofriendly amphiphilic polymers that comprise methoxy poly(ethylene glycol)-poly(cyclohexane-1,4-diyl acetone dimethyleneketal) (mPEG-PCADK) and mPEG-poly((cyclohexane86.7%, 1,5-pentanediol13.3%)-1,4-diyl acetone dimethylene ketal) (PK3) for the targeted delivery of SOD. The novel polymers could self-assemble into micellar nanoparticles with favorable hydrolysis kinetics, biocompatibility, long circulation time, and inflammation-targeting effects. These materials generated a better pH-response curve and exhibited better hydrolytic kinetic behavior than PCADK and PK3. The polymers showed good biocompatibility with protein drugs and did not induce an acidic microenvironment during degradation in contrast to materials such as PEG-block-poly(lactic-co-glycolic acid) (PLGA) and PLGA. The SOD that contained reverse micelles based on mPEG2000-PCADK exhibited good circulation and inflammation-targeting properties. Pharmacodynamic results indicated exceptional antioxidant and anti-inflammatory activities in a rat adjuvant-induced arthritis model and a rat peritonitis model. These results suggest that these copolymers are ideal protein carriers for targeting inflammation treatment.
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高影响因子
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