REACTIVE & FUNCTIONAL POLYMERS
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2021
·
IF 3.975
Yue Zhang,Lizhen Yu,Jun Zhu,Renmin Gong
In this paper, a novel grafted polymer (folate and carboxymethyl-β-cyclodextrin grafted trimethyl chitosan, FCT) was synthesized. Then the FCT nanoparticles (FCT NPs) were fabricated by ionic gelation and the potential of NPs as co-carrier of doxorubicin and siRNA was evaluated. The physicochemical properties of grafted polymer and NPs were characterized and analyzed by fourier transforms infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential and polydispersity index (PDI). The results showed the diameter of NPs ranged from 190 to 240 nm with polydispersity index of 0.192 and zeta potential of +21mv. The prepared NPs exhibited satisfactory drug loading capacity and encapsulation efficiency to doxorubicin and siRNA-survivin. Meanwhile, the prepared NPs could effectively protect siRNA-survivin from degradation of serum RNAase for a long time. Both drugs encapsulated in NPs all exhibited pH-dependent controlled sustained release characteristics and the cytotoxicity study testified that drug drug-loaded FCT NPs significantly improved the efficacy of antitumor drugs . The novel graft polymer was expected to become the co-carrier of anticancer and gene drugs in future with broad application prospects.
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高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2021
·
IF 8.128
Yalei Miao,Yecheng Feng,Jie Bai,Zhongyi Liu,Xubo Zhao
Rapid progress has been made for mesoporous silica nanoparticle (MSN) in recent years; however, efforts to fabricate MSN with adjustable size have been met with limited advancement in drug delivery, especially for the synthesis of MSN with adjustable size in the range of 150–300 nm. Herein we report the construction of a series of MSNs with adjustable specific surface area, size, and pore structure, depending on the different silicon monomers selected. The optimized MSN showed large specific surface area and appropriate size distribution for efficiently anchoring doxorubicin (DOX) through the imine linkage formed. Based on the remarkable features of the unique MSN, a novel MSN-based drug delivery system was prepared through the introduction of polydopamine/manganese oxide (PDA/MnO 2 ) coating, which reduced the premature leakage of drugs in physiological environments, and yet facilitated drug release when destroyed by responding to endogenous glutathione (GSH) at the tumor sites. Notably, the transformation of MnO 2 to Mn 2+ resulted in the collapse of the PDA/MnO 2 coating, which facilitated drug release and therefore indicated the controlled release feature. It was demonstrated that the drug-loaded MSN-based drug delivery system delivered drugs into cancer cells and showed effective inhibition against cancer cell growth. These results suggested that the emergence of MSN with adjustable size can expand the application of MSN in drug delivery.
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高影响因子
POLYMER INTERNATIONAL
·
2021
·Vol. 70
·期 12
·1717-1724
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IF 2.99
Lei Wang,Yifan Huang,Binjie Xin,Tingxiao Li
Electrospun core–shell nanofibers have aroused attention in drug delivery systems and tissue engineering because of the latent structures which can encapsulate various drugs and obtain tailored release profiles. Here, poly( l -lactide- co -ε-caprolactone) (PLCL) with gelatin (GE) blends were employed to electrospin the shell of core–shell nanofibers which could act as a protection layer for the controlled released behavior of the model drug doxorubicin hydrochloride (DOX). Core–shell nanofiber membranes with different drug loaded amounts were fabricated and the corresponding drug release behaviors were researched. The surface morphology of the obtained nanofibers was assessed by SEM and the structure of the core–shell nanofibers were observed by inverted fluorescence microscopy and TEM. The hydrophilicity was evaluated by water contact angle testing and the results indicated that the obtained fibers all possess good hydrophilicity. The mechanical properties of the fiber membranes were evaluated by tensile testing. Exploring the composition of the fiber membranes by Fourier transform infrared spectroscopy proved that DOX existed in the drug-loaded fiber membranes. In vitro release was evaluated by UV–visible spectroscopy and the accumulative release curves of DOX showed that increasing drug rates would lead to increasing cumulative release amounts but decreasing cumulative drug release rates. The results indicated that drugs encapsulated in PLCL/GE core–shell nanofiber material would be efficient and a potential material for drug delivery systems. © 2021 Society of Chemical Industry
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高影响因子
Nanomaterials
·
2020
·Vol. 10
·期 9
·1655
·
IF 4.324
Yuqiong Shi,Yuxuan Wang,Jinhua Zhu,Wei Liu,Md. Zaved H. Khan,Xiuhua Liu
MIL-based molecularly imprinted polymer (MIP) nanocomposites were successfully synthesized through a simple and versatile stirring auxiliary encapsulation method. MIP as a carrier has been applied to the highly efficient selective recognition and sustained release of doxorubicin hydrochloride (DOX). The adsorption mechanism and release behavior of[email protected]in vitro were also discussed. Adsorption studies showed that MIP using DOX as template had specific selectivity to DOX, and its optimal drug loading efficiency reached 97.99%. The adsorption isotherm accorded with Freundlich models. The cumulative release curve showed that at the conditions of pH 5.5 and 7.4, the nanomaterials have a slow-release effect on the release of DOX. In addition, the cytotoxicity and bioactivity of MIP nanoparticles on HepG2 and HL-7702 cell lines measured by MTT assay also proved their low toxicity and biological activity. The cell activity of HepG2 and HL-7702 incubated with MIP for 24 h was 69.9% and 76.07%, respectively. These results collectively illustrated that the MIP nano-materials synthesized in this study can be efficiently employed to the drug delivery systems.Keywords:MIP;nanocomposites;drug delivery;DOX;controlled release
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高影响因子
International Journal of Medical Sciences
·
2020
·
IF 2.523
Ke Li,Wenhua Zhan,Min Jia,Yufeng Zhao,Yingguang Liu,Rajiv Kumar Jha,Liansuo Zhou
Background : Combination chemotherapy plays an important role in the clinical therapy of non-small cell lung cancer (NSCLC). However, the pharmacokinetic differences between drugs are an insurmountable barrier in traditional treatment. For the synergistic therapy of NSCLC, synergistic nanoparticles (EDS NPs) loaded with both an EGFR inhibitor and doxorubicin (DOX) were designed and prepared. Methods : Erlotinib, apatinib and icotinib were evaluated for optimal combination with DOX in treatment of NSCLC via CCK-8 assay. Then the cationic amphipathic starch (CSaSt) and hyaluronic acid (HA) were applied to coencapsulate DOX and EGFR inhibitor to form the EDS NPs. EDS NPs were evaluated in NSCLC cell lines (A549, NCI-H1975 and PC9) and NSCLC xenograft mouse models. Results : Icotinib was found to be the optimal synergistic drug in combination with DOX in the tested. Subsequently, icotinib and DOX were coencapsulated in the NPs. EDS NPs were roughly spherical with an average size of 65.7±6.2 nm and possessed stable loading and releasing properties. In the in vitro investigation, EDS NPs could efficiently deliver payloads into cells, exhibited cytotoxicity and produced strong anti-migration properties. In vivo hypotoxicity was confirmed by acute toxicity and hemolytic assays. The in vivo distribution showed that EDS NPs could enhance accumulation in tumors and decrease nonspecific accumulation in normal organs. EDS NPs significantly promoted the in vivo synergistic effects of icotinib and DOX in the mouse model. Conclusions : The study suggests that EDS NPs possess noteworthy potential for development as therapeutics for NSCLC clinical chemotherapy.
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高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2020
·Vol. 72
·期 4
·496-506
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IF 2.571
Zha Liqiong,Wang Beilei,Qian Jiajia,Fletcher Brock,Zhang Caiyun,Dong Qiannian,Chen Weidong,Hong Lufeng
ObjectivesZein nanoparticles (Zein NPs) were used as a hydroxyapatite (HA) biomineralization template to generate HA/Zein NPs. Doxorubicin hydrochloride (DOX) was loaded on HA/Zein NPs (HA/Zein-DOX NPs) to improve its pH-sensitive release, bioavailability and decrease cardiotoxicity.MethodsHA/Zein-DOX NPs were prepared by phase separation and biomimetic mineralization method. Particle size, polydispersity index (PDI), Zeta potential, transmission electron microscope, X-ray diffraction and Fourier-transform infrared spectroscopy of HA/Zein-DOX NPs were characterized. The nanoparticles were then evaluated in vitro and in vivo.Key findingsThe small PDI and high Zeta potential demonstrated that HA/Zein-DOX NPs were a stable and homogeneous dispersed system and that HA was mineralized on Zein-DOX NPs. HA/Zein-DOX NPs showed pH-sensitive release. Compared with free DOX, HA/Zein-DOX NPs increased cellular uptake which caused 7 times higher in-vitro cytotoxicity in 4T1 cells. Pharmacokinetic experiments indicated the t1/2β and AUC0–t of HA/Zein-DOX NPs were 2.73- and 3.12-fold higher than those of DOX solution, respectively. Tissue distribution exhibited HA/Zein-DOX NPs reduced heart toxicity with lower heart targeting efficiency (18.58%) than that of DOX solution (37.62%).ConclusionIn this study, HA/Zein-DOX NPs represented an antitumour drug delivery system for DOX in clinical tumour therapy with improved bioavailability and decreased cardiotoxicity.
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2021
·Vol. 19
·期 1
·1-16
·
IF 10.435
Xiao Jianmin,Yan Miao,Zhou Ke,Chen Hui,Xu Zhaowei,Gan Yuehao,Hong Biao,Tian Geng,Qian Junchao,Zhang Guilong,Wu Zhengyan
The cell membrane is widely considered as a promising delivery nanocarrier due to its excellent properties. In this study, self-assembled Pseudomonas geniculate cell membranes were prepared with high yield as drug nanocarriers, and named BMMPs. BMMPs showed excellent biosafety, and could be more efficiently internalized by cancer cells than traditional red cell membrane nanocarriers, indicating that BMMPs could deliver more drug into cancer cells. Subsequently, the BMMPs were coated with nanoselenium (Se), and subsequently loaded with Mn2+ ions and doxorubicin (DOX) to fabricate a functional nanoplatform (BMMP-Mn2+/Se/DOX). Notably, in this nanoplatform, Se nanoparticles activated superoxide dismutase-1 (SOD-1) expression and subsequently up-regulated downstream H2O2 levels. Next, the released Mn2+ ions catalyzed H2O2 to highly toxic hydroxyl radicals (·OH), inducing mitochondrial damage. In addition, the BMMP-Mn2+/Se nanoplatform inhibited glutathione peroxidase 4 (GPX4) expression and further accelerated intracellular reactive oxygen species (ROS) generation. Notably, the BMMP-Mn2+/Se/DOX nanoplatform exhibited increased effectiveness in inducing cancer cell death through mitochondrial and nuclear targeting dual-mode therapeutic pathways and showed negligible toxicity to normal organs. Therefore, this nanoplatform may represent a promising drug delivery system for achieving a safe, effective, and accurate cancer therapeutic plan.
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CARBOHYDRATE POLYMERS
·
2019
·
IF 6.044
Ping Liu,Nana Chen,Lei Yan,Fei Gao,Dongsheng Ji,Shijiao Zhang,Litao Zhang,Yuqin Li,Yuliang Xiao
The purpose of this study was to ascertain the effect of chondroitin sulphate-modified doxorubicin (Dox) nanoparticles on enhancing the tumour-targeting effect and tumour growth inhibition effect of doxorubicin both in vitro and in vivo . The chondroitin sulphate-doxorubicin conjugate and its poly(lactic-co-glycolic acid) (PLGA) nanoparticles (CS-Dox-PLGA) were successfully synthesised, and then characterized by Fourier-transform infrared spectroscopy (FTIR), proton magnetic resonance ( 1 HNMR), thermogravimetric analysis/differential scanning calorimetry (TGA/DSC), transmission electron microscope (TEM), zeta potential and laser light scattering. Taking advantage of the enhanced permeability and CD44-mediated endocytosis, CS-Dox-PLGA showed excellent capacity for penetrating the peripheral tumour barrier and into the nucleus of tumour cells. The CS-Dox-PLGA cellular uptake was improved and exhibited a significantly higher level of cytotoxicity in U251 cells. After intravenous administration, the CS-Dox-PLGA showed good pharmacokinetic properties and excellent U251-induced tumour inhibition with low cardiac toxicity. Therefore, CS-Dox-PLGA with low cardiac toxicity and good anti-tumour ability might be a better choice for Dox in clinical practice.
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高影响因子
BIOMACROMOLECULES
·
2019
·
IF 5.667
Yanqian Wu,Yi Xiao,Yushu Huang,Yanyun Xu,Donglei You,Wei Lu,Jiahui Yu
A biodegradable brush-type copolymer PHF-g-(PCL-PEG) based on a cleavable polyacetal backbone and biodegradable side chain modified with polyethylene glycol (PEG) was synthesized in this paper. This particular structure was directional to facilitate the formation of spherical or rod-shaped micelles. Flow cytometry showed that rod-shaped micelles displayed enhanced cellular uptake compared to spherical micelles. Rod-shaped micelles were selected to investigate their drug delivery abilities in detail. In vitro experiments verified the pH-triggered drug release of DOX-loaded micelles, and the release rate of doxorubicin (DOX) was 77% at pH 5.0 and 26% at pH 7.4. In drug-release kinetic analysis, a double-exponential model achieved the best fit. The copolymer appeared to be almost nontoxic, while the DOX-loaded micelles showed equivalent cytotoxicity compared to DOX at high concentration. The endocytosis of DOX-loaded micelles was two times that of DOX. Our findings suggest that the pH-sensitive brush type copolymer could be a possible carrier in drug delivery.
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Polymer Chemistry
·
2018
·Vol. 10
·期 4
·512-525
·
IF 4.927
Yanan Tan,Xiqin Yang,Suhuan Dai,Keke Lian,Lijuan Wen,Yun Zhu,Tingting Meng,Xuan Liu,Hong Yuan,Fuqiang Hu
The selective delivery of DOX into tumor mitochondria in vitro and in vivo, which can be achieved with the aid of a skeletal polymer with positively charged and lipophilic character, may significantly promote its antitumor efficiency as well as eliminate its severe cardiotoxicity. In this study, we developed a polycationic glycolipid polymer (CSOSA) as a skeletal nanomaterial, which was further modified with lipophilic (4-carboxybutyl) triphenylphosphonium bromide (CTPP) cations to form the mitochondria-targeted polymer C-P-CSOSA. In vitro, C-P-CSOSA polymer micelles were internalized more by tumor cells than normal cells and exhibited rapid lysosomal escape capability due to their strong proton buffering ability. When loaded with DOX, the C-P-CSOSA/DOX micelles could selectively target mitochondria in tumor cells and remarkably activate the mitochondrial apoptosis signaling pathway. Importantly, the C-P-CSOSA polymer exhibited significant mitochondrial co-localization in vivo. Moreover, C-P-CSOSA/DOX demonstrated the highest tumor-inhibition rate (75.0%), when compared with CSOSA/DOX (44.8%) and DOX·HCl (55.0%). Meaningfully, C-P-CSOSA/DOX did not cause obvious organ damage and exhibited the longest survival time, indicating the low toxicity of this polymer. This study opens up new avenues for the future clinical translation of mitochondrial-targeted drug delivery systems.
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JOURNAL OF MATERIALS SCIENCE
·
2014
·Vol. 50
·期 6
·2429-2442
·
IF 2.305
Zhang Han,Xue Yanan,Huang Juan,Xia Xiaoyang,Song Meifang,Wen Kaikai,Zhang Xiaoxiao,Luo Xiaogang,Cai Ning,Long Sihui,Yu Faquan
A charge reversible, magnetic-targeted, and pH-responsive nano therapy system assembled from citraconic-modified dextran (Dex–COOH), glycine-stabilized superparamagnetic iron oxide nanoparticles (SPION–NH 2 ), and doxorubicin (DOX) through electrostatic interaction was designed for delivering therapeutics to tumor cells. Dex–COOH was first synthesized to build the pH-sensitive citraconic amide bond and further render charge reversal upon the cleavage of the linkage. The SPION–NH 2 anchored in the nanocarrier endows the carrier with magnetic migration. The vibrating sample magnetometer analysis exhibits the superparamagnetic behavior, and the magnetic saturation value is estimated to be 39.6 emu (g Fe) −1 . The change of size and the reversal of zeta potential from negative to positive in acidic environment confirmed these expected responsibilities. The DOX-loaded nanocarriers contain DOX up to 13.0 wt%. An in vitro release profile demonstrated an efficient DOX release of 80 % at pH 5.0 while of 27 % at pH 6.8 and 13 % at pH 7.4, suggesting a pH-induced release mechanism. Microscopic images of Prussian blue staining, quantification of cellular iron and protein concentration displayed apparent iron uptake by HeLa cells. Confocal laser scanning microscopy observations revealed that the nanocarriers could efficiently deliver and release DOX into the nuclei of HeLa cells. MTT assays testified that DOX-loaded nanocarrier exhibited high anti-tumor activity with IC 50 of 0.7 μg mL −1 , while plain nanocarriers were practically non-toxic. This drug delivery system has shown the ability to improve the chemotherapeutic efficacy and to reduce the side effects, indicating great potential for delivery of drugs to the targeted sites in patients.
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高影响因子
Asian Journal of Pharmaceutical Sciences
·
2014
·
IF 0
Erxi Che,Long Wan,Ying Zhang,Qinfu Zhao,Xiling Han,Jia Li,Jia Liu,Siling Wang
In this study, phosphonate-terminated magnetic mesoporous nanoparticles (pMMSNs) was designed by incorporation of MNPs in the center of mesoporous silica nanoparticles (MSNs) and followed by grafting phosphonate group on to the surface of MMSNs. The carrier exhibited a typical superparamagnetic feature and the saturation magnetization was 4.89 emu/g measured by vibrating sample magnetometer (VSM). pMMSNs had a spherical morphology and a pore size of 2.2 nm. From N 2 adsorption-desorption analysis, pMMSNs had a surface area of 613.4 m 2 /g and a pore volume of 0.78 cm 3 /g. Phosphonate modification improved the colloidal stability of MMSNs, and the hydrodynamic diameter of pMMSNs was around 175 nm. The hydrophilic phosphonate group significantly enhanced the negative surface charge of MMSNs from −19.3 mV to −28.8 mV pMMSNs with more negative surface charge had a 2.3-fold higher drug loading capacity than that of MMSNs. In addition, the rate and amount of release of doxorubicin (DOX) from DOX/pMMSNs was pH-dependent and increased with the decrease of pH. At pH 7.4, the release amount was quite low and only approximately 17 wt% of DOX was released in 48 h. At pH 5.0 and 3.0, the release rate increased significantly and the release amount achieved 31 wt% and 60 wt% in 48 h, respectively. To evaluate the magnetic targeting performance of pMMSNs, FITC labeled pMMSNs was injected into mice bearing S180 solid tumor. FITC labeled pMMSNs controlled by an external magnetic field showed higher tumor accumulation and lower normal tissue distribution.
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