ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Lan Wu,Lin-Ping Wu,Jingya Wu,Jin Sun,Zhonggui He,Cristina Rodríguez-Rodríguez,Katayoun Saatchi,Lea Ann Dailey,Urs O. Häfeli,Dongmei Cun,Mingshi Yang
Pulmonary delivery of small interfering RNA (siRNA)-based drugs is promising in treating severe lung disorders characterized by the upregulated expression of disease-causing genes. Previous studies have shown that the sustained siRNA release in vitro can be achieved from polymeric matrix nanoparticles based on poly(lactide-co-glycolide) (PLGA) loaded with lipoplexes (LPXs) composed of cationic lipid and anionic siRNA (lipid–polymer hybrid nanoparticles, LPNs). Yet, the in vivo efficacy, potential for prolonging the pharmacological effect, disposition, and safety of LPNs after pulmonary administration have not been investigated. In this study, siRNA against enhanced green fluorescent protein (EGFP-siRNA) was either assembled with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) to form LPX or co-entrapped with DOTAP in PLGA nanoparticles to form LPNs. The disposition and clearance of LPXs and LPNs in mouse lungs were studied after intratracheal administration by using single-photon emission computed tomography/computed tomography (SPECT/CT) and gamma counting. Fluorescence spectroscopy, Western blot, and confocal laser scanning microscopy were used to evaluate the silencing of the EGFP expression mediated by the LPXs and LPNs after intratracheal administration to transgenic mice expressing the EGFP gene. The in vivo biocompatibility of LPXs and LPNs was investigated by measuring the cytokine level, total cell counts in bronchoalveolar lavage fluid, and observing the lung tissue histology section. The results showed that the silencing of the EGFP expression mediated by LPNs after pulmonary administration was both prolonged and enhanced as compared to LPXs. This may be attributed to the sustained release characteristics of PLGA, and the prolonged retention in the lung tissue of the colloidally more stable LPNs in comparison to LPXs, as indicated by SPECT/CT. The presence of PLGA effectively alleviated the acute inflammatory effect of cationic lipids to the lungs. This study suggests that PLGA-based LPNs may present an effective formulation strategy to mediate sustained gene silencing effects in the lung via pulmonary administration.
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高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2020
·
IF 5.88
Daqian Gao,Zongliang Wang,Zhenxu Wu,Min Guo,Yu Wang,Zhenhua Gao,Peibiao Zhang,Yoshihiro Ito
Biodegradable polyesters have been widely used as rigid biomedical apparatus because of high mechanical properties but few flexible implants. Herein, we report a flexible poly(lactide- co -glycolide) (PLGA) scaffold using a rapid in situ formation system based on phase separation by solvent exchange deposition modeling (SEDM), which was different from traditional 3D printing of fused deposition modeling (FDM). The FDM printed product was rigidity, its Young's modulus was approximate 2.6 times higher than that of SEDM printed sample. In addition, the thickness of the solidified ink would not shrink during the SEDM printing process, its surface had nano-/micro pores in favor of protein immobilization and cell adhesion. Then a flexible bilayered scaffold with nano-/microstructure was constructed combing SEDM with electrospinning technology for skin substitute, wherein the SEDM printed sample acted as a sub-layer for cell and tissue ingrowth, the densely packed electrospun nanofibers served as an upper-layer improving the sub-layer's tensile strength by 57.07% and preventing from bacteria as physical barrier. Ultimately, the bilayered scaffold immobilized epidermal growth factor (EGF) by a bioorthogonal approach was successfully applied to facilitate full-thickness wound healing of rats.
研究领域:
生物医学工程
·
组织工程
·
再生医学
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PubMed
高影响因子
BIOMATERIALS
·
2013
·
IF 7.604
Jingbin Huang,He Zhang,Yuan Yu,Yan Chen,Dong Wang,Guoqing Zhang,Guichen Zhou,Junjie Liu,Zhiguo Sun,Duxin Sun,Ying Lu,Yanqiang Zhong
To develop biodegradable docetaxel-loaded self-assembled nanoparticles of poly ( d , l -lactide-co-glycolide)/hyaluronic acid block copolymers were successfully synthesized. These copolymers could form nanoparticles with small size (<200 nm), an acceptable CMC (∼7.9 mg/L), typical core/shell structure and superior stability in one week. DTX-loaded PLGA 502H -b-HA 5.6k nanoparticles (DTX/SANPs) showed a biphasic release pattern within 120 h, and exhibited enhanced cytotoxicity toward CD44-overexpressing MDA-MB-231 cells. Cellular uptake study indicated that PLGA 502H -b-HA 5.6k nanoparticles (SANPs) were taken up in MDA-MB-231 cells by CD44-mediated endocytosis . Pharmacokinetics study revealed DTX/SANPs could prolong the circulation of DTX in the blood. In vivo studies demonstrated that SANPs exhibited enhanced tumor targeting and antitumor activity with lower systemic toxicity. In conclusion, DTX/SANPs have great potential for targeted chemotherapy for CD44-overexpressing breast cancer.
研究领域:
药剂学
·
肿瘤学
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PubMed
高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 48
·9908-9922
·
IF 6.331
Qi Xu,Qiuting Li,Zhe Yang,Piao Huang,Han Hu,Zhimin Mo,Zizhen Qin,Zushun Xu,Tianyou Chen,Shengli Yang
Lenvatinib (LT) is gradually replacing sorafenib as an alternative targeted drug against advanced hepatocellular carcinoma (HCC). However, the anticancer effects of LT are still limited because of its low cytotoxicity, multidrug resistance (MDR), and tumor relapse. Herein, we constructed a smart biophotonic nanoplatform to overcome the barriers preventing high performance. LT and copper sulfide nanocrystals (Cu2−xS NCs) with excellent photothermal properties in the near-infrared-II (NIR-II) zone were co-encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) through nanoprecipitation. Both in vitro and in vivo evaluations demonstrated that Cu2−xS NCs enhanced the anticancer efficacy of LT, without recurrence. In addition, the presence of copper ions could allow glutathione (GHS) to be consumed and oxygen to be produced, likely suppressing the expression of P-glycoprotein (P-gp) and overcoming the issue of MDR relating to LT. More importantly, synergistic chemo-photothermal therapy with LT and Cu2−xS NCs was more effective than any single therapy or theoretical combination. This nanoplatform is promising for advancing future LT-based treatment strategies for HCC therapy.
研究领域:
肿瘤学
·
纳米医学
·
药物递送系统
·
生物材料
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高影响因子
EUROPEAN POLYMER JOURNAL
·
2021
·
IF 4.598
Junwei Xu,Kun Li,Meili Liu,Xuenan Gu,Ping Li,Yubo Fan
Rod-like microparticles are important drug delivery systems for their large specific surface area and high cell uptake rate. However, complex preparation methods, such as mechanical stretching and cutting after electrospinning restrict applications of rod-like microparticles. In this study, uniformly sized microrods were fabricated via one-step electrospray by using poly(lactide-co-glycolide) (PLGA) solutions with low viscosity, mainly low concentration, and low molecular weights. In contrast to previous results that polymer beads are usually obtained with low-concentration precursor solutions, we prepared 0.5–2.0 μm diameter and 4–20 μm long microrods when the concentration of the solution and molecular weight of the polymer were further decreased. Moreover, the aspect ratio of the microrods decreased significantly after upregulating the loading voltage, adding salt, and using high permittivity solvents. It is suggested that the formation of microrods with an aspect ratio of 4.51· N ( N = 1, 2, 3…) was based on the surface wave theory, which was tallied with the experimental data. Furthermore, the doxorubicin(DOX)@PLGA microrods showed higher entrapment efficiency and drug-loading capacity as a drug delivery system compared with those of [email protected] microspheres. Microrods have the potential for a broader range of applications in biomedicine due to the easy preparation process of one-step electrospray.
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高影响因子
RSC Advances
·
2016
·Vol. 6
·期 28
·23693-23701
·
IF 3.289
Jiulong Zhang,Kang Chen,Ying Ding,Xiu Xin,Wenpan Li,Mengjun Zhang,Haiyang Hu,Mingxi Qiao,Xiuli Zhao,Dawei Chen
pH-Sensitive copolymers have been widely used in drug delivery systems to selectively enhance drug release at tumor sites. Herein, dextran (DX) was conjugated with poly(lactide-co-glycolide) (PLGA) and histidine (His) to prepare a pH-responsive nanocarrier, dextran-g-poly(lactide-co-glycolide)-g-histidine (HDP) micelles, for the delivery of antitumor drugs. Different grafting ratio HDP micelles were synthesized and prepared successfully and confirmed by the critical micelle concentration (CMC) and particle size distribution (PSD). In vitro drug release showed that the release behaviour of paclitaxel (PTX) loaded HDP micelles was pH-dependent. All blank micelles were nontoxic in the in vitro cytotoxicity assay. In an MTT assay, PTX-loaded HDP micelles with medium grafting ratios (MHDP) showed the highest cytotoxicity against MCF-7 cells. Cellular uptake experiments revealed that these pH-sensitive micelles could be taken up effectively and PTX could be delivered into the cytoplasm to reach the antitumor effect. NIR fluorescence imaging experiments demonstrated that HDP micelles could specifically accumulate in tumor sites via enhancing the permeability and retention (EPR) effect to reduce their systematic toxicity. In vivo antitumor activities showed that HDP micelles could effectively inhibit tumor growth and prolong survival time compared with free PTX solution. These results confirm that the biocompatible pH-responsive HDP micelles are a novel nanocarrier for the intracellular delivery of PTX.
研究领域:
药剂学
·
高分子化学
·
癌症研究
·
药物递送系统
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高影响因子
MACROMOLECULAR BIOSCIENCE
·
2015
·Vol. 15
·期 8
·1070-1080
·
IF 3.851
Tianlin Gao,Ning Zhang,Zongliang Wang,Yu Wang,Ya Liu,Yoshihiro Ito,Peibiao Zhang
In this study, insulin-like growth factor 1 (IGF-1) was successfully immobilized on the poly(lactide-co-glycolide)/hydroxyapatite (PLGA/HA) and pure PLGA microcarriers via polydopamine (pDA). The results demonstrated that the pDA layer facilitated simple and highly efficient immobilization of peptides on the microcarriers within 20 min. Mouse adipose-derived stem cells (ADSCs) attachment and proliferation on IGF-1-immobilized microcarriers were much higher than non-immobilized ones. More importantly, the IGF-1-immobilized PLGA/HA microcarriers significantly increased alkaline phosphatase (ALP) activity and expression of osteogenesis-related genes of ADSCs. Therefore, it is considered that the IGF-1-decorated PLGA/HA microcarriers will be of great value in the bone tissue engineering.
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PubMed
高影响因子
Biomedical Materials
·
2021
·Vol. 16
·期 6
·064101
·
IF 3.715
Xinyu Wu,Jie Ding,Peifang Xu,Xue Feng,Zhaoyi Wang,Tong Zhou,Chenxi Tu,Wangbei Cao,Jieqi Xie,Liwen Deng,Liyin Shen,Yang Zhu,Zhongru Gou,Changyou Gao
The modulation of inflammation in tissue microenvironment takes an important role in cartilage repair and regeneration. In this study, a novel hybrid scaffold was designed and fabricated by filling a reactive oxygen species (ROS)-scavenging hydrogel (RS Gel) into a radially oriented poly(lactide-co-glycolide) (PLGA) scaffold. The radially oriented PLGA scaffolds were fabricated through a temperature gradient-guided phase separation and freeze-drying method. The RS Gel was formed by crosslinking the mixture of ROS-responsive hyperbranched polymers and biocompatible methacrylated hyaluronic acid (HA-MA). The hybrid scaffolds exhibited a proper compressive modulus, good ROS-scavenging capability, and cell compatibility. In vivo tests showed that the hybrid scaffolds significantly regulated inflammation and promoted regeneration of hyaline cartilage after they were implanted into full-thickness cartilage defects in rabbits for 12 w. In comparison with the PLGA scaffolds, the neo-cartilage in the hybrid scaffolds group possessed more deposition of glycosaminoglycans and collagen type II, and were well integrated with the surrounding tissue.
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高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
·
2017
·Vol. 135
·期 9
·45732
·
IF 1.86
Xiangke Sun,Xue Liu,Chenglong Li,Yuandou Wang,Li Liu,Feng Su,Suming Li
A series of poly(ɛ-caprolactone)–poly(ethylene glycol) (PCL-PEG) and poly(ɛ-caprolactone/glycolide)–poly(ethylene glycol) [P(CL/GA)-PEG] diblock copolymers were prepared by ring-opening polymerization of ɛ-caprolactone or a mixture of ɛ-caprolactone and glycolide using monomethoxy PEG (mPEG) as macroinitiator and Sn(Oct) 2 as catalyst. The resulting copolymers were characterized using 1 H-NMR, gel permeation chromatography, differential scanning calorimetry, and wide-angle X-ray diffraction. Copolymer micelles were prepared using the nanoprecipitation method. The morphology of the micelles was spherical or worm-like as revealed by transmission electron microscopy, depending on the copolymer composition and the length of the hydrophobic block. Introduction of the glycolide component, even in small amounts (CL/GA = 10), disrupted the chain structure and led to the formation of spherical micelles. Interestingly, the micelle size decreased with the encapsulation of paclitaxel. Micelles prepared from mPEG5000-derived copolymers exhibited better drug loading properties and slower drug release than those from mPEG2000-derived copolymers. Drug release was faster for copolymers with shorter PCL blocks than for those with longer PCL chains. The introduction of glycolide moieties enhanced drug release, but the overall release rate did not exceed 10% in 30 days. In contrast, drug release was enhanced in acidic media. Therefore, these bioresorbable micelles and especially P(CL/GA)-PEG micelles with excellent stability, high drug loading content, and prolonged drug release could be promising for applications as drug carriers. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135 , 45732.
研究领域:
生物材料
·
药剂学
·
高分子化学
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高影响因子
INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
·
2023
·
IF 4.2
Shuo Tang,Bingli Ma,Liuyun Jiang,Yan Zhang,Shengpei Su
To obtain an ideal guided bone regeneration (GBR) membrane, in this study, a novel degradable bilayered composite membrane loaded with vancomycin (VCM) was constructed by an electrospun layer of nanohydroxyapatite/poly(lactide-co-glycolide) (n-HA/PLGA) and a casting layer of a bamboo fiber (BF). The effects of different addition methods and contents of n-HA and VCM on the structure, hydrophilicity, tensile strength, degradation, drug release, antibacterial properties, and cell proliferation of the composite membrane were investigated. Results indicated that the electrospun layer and the casting layer were closely combined by a chitosan (CS) adhesive solution, and the addition of higher n-HA content into PLGA as the electrospun layer was advantageous to improve the hydrophilicity of the composite membrane and slow down the degradation. Moreover, the BF casting layer endowed the composite membrane with better tensile strength, especially the introduction of VCM into a CS solution displayed better bone-like apatite deposition, faster drug release rate, and better cell proliferation than that into the electrospun layer, so that it presented better antibacterial effect. All results demonstrated that the degradable n-HA-PLGA/BF bilayered composite membrane loaded with VCM in the CS adhesive solution displayed appropriate mechanical strength, degradation, antibacterial properties, and biocompatibility, which had great promise to be used as a GBR membrane.
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高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2017
·
IF 1.9
Li Xu,Caifeng Wan,Jing Du,Hongli Li,Xuesong Liu,Hong Yang,Fenghua Li
Breast cancer is the leading cause of cancer-related deaths in women and earlier detection can substantially reduce deaths from breast cancer. Polymers with targeted ligands are widely used in the field of molecular ultrasound imaging and targeted tumor therapy. In our study, the nanotheranostic agent was fabricated through filling perfluoropropane (C3F8) into poly(d,l-lactic-co-glycolic acid) nanoparticles (PLGA NPs), followed by the formation of gold nanoshell on the surface, then conjugated with anti p53 antibody which has high specificity with the p53 protein overexpressing in breast cancer. The average diameter of the gold nanoshelled PLGA NPs carrying anti p53 antibody (p53-PLGA@Au NPs) was 247 ± 108.2 nm. The p53-PLGA@Au NPs had well-defined spherical morphology and hollow interiors observed by electron microscope, and had a good photothermal effect under the irradiation of an 808 nm laser. The results of laser scanning confocal microscope (LSCM) and flow cytometer (FCM) indicated the specific targeting of p53-PLGA@Au NPs conjugating with breast cancer MCF-7 cells overexpressing p53 protein in vitro. Also the ultrasound imaging experiments in vitro showed that p53-PLGA@Au NPs were suitable for ultrasound contrast imaging. In conclusion, the p53-PLGA@Au NPs are demonstrated to be novel targeted UCAs and may have potential applications in the early diagnosis and targeted near-infrared (NIR) photothermal therapy of breast cancer in the future.
研究领域:
肿瘤学
·
纳米技术
·
生物医学工程
·
药学
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DOI
PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2016
·Vol. 12
·期 7
·1463-1477
·
IF 3.929
Huang Jingbin,Tao Chun,Yu Yuan,Yu Feifei,Zhang He,Gao Jie,Wang Dong,Chen Yan,Gao Jing,Zhang Guoqing,Zhou Guichen,Liu Junjie,Sun Zhiguo,Sun Duxin,Zou Hao,Xu Hao,Lu Ying,Zhong Yanqiang
Breast cancer stem cells (BCSCs) are implicated in the initiation and progression of breast cancer and are responsible for metastasis and recurrence. In this study, we attempted to simultaneously target differentiated breast cancer cells (DBCCs) and BCSCs by using a combination of docetaxel
(DTX)- and sulforaphane (SFN)-loaded poly(D, L-lactide-coglycolide)/hyaluronic acid (PLGA-b-HA)-based nanoparticles. BCSCs were identified as having an ESA+CD44+CD24– phenotype, which exhibited docetaxel resistance. Drug-loaded nanoparticles exhibited
enhanced cytotoxicity towards both DBCCs and BCSCs compared with free drugs. SFN-loaded nanoparticles were more effective in inhibiting BCSCs than free SFN in vitro by down-regulating β-catenin expression. In vivo analysis of anti-tumor activity showed that the combination
therapy with DTX- and SFN-loaded nanoparticles had the strongest antitumor efficacy. In vivo analysis of anti-BCSCs activity showed that the self-renewal ability of BCSCs was strongly inhibited in DTX- and SFN-loaded nanoparticle-treated groups. In conclusion, the combination of SFN-
and DTX-loaded PLGA-b-HA nanoparticles shows therapeutic potential in the treatment of breast cancer by simultaneously targeting DBCCs and BCSCs.
研究领域:
肿瘤学
·
药剂学
·
分子生物学
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PubMed
高影响因子
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