Current Drug Delivery
·
2024
·Vol. 21
·期 2
·295-307
·
IF 2.8
Yang Yaxin,Shi Wei,Zhang Ziyi,Gong Fawu,Feng Xuman,Guo Chenxi,Qi Yajuan,Liu Zhanjun
Introduction: Anti-inflammatory medications, in particular aspirin, have chemopreventive and anticancer adjuvant effects on specific types of cancers, according to ongoing anti-tumor research. Additionally, efforts have been made to transform Poly(salicylic acid) (PSA) into delivery-related
nanocarriers. to transport anticancer medications into nanocarriers. However, tumor cell targeting and tumor selectivity were lacking in the salicylic acid polymer-based nanocarriers, preventing them from performing to their full potential. Objective: The objective of this study is to
prepare targeting and reduction-responsive poly pre-drug nanocarriers (HA-ss-PSA NPs) and to investigate the feasibility of delivering adriamycin (DOX) as nanocarriers. Methods: The structures of the polymers were confirmed by nuclear magnetic resonance hydrogen spectroscopy (1H-NMR)
and infrared spectroscopy (IR); the encapsulation rate and drug loading of DOX-loaded nanoparticles were determined by HPLC; and the anti-tumor effects of the carriers were evaluated by MTT experiments and in vivoexperiments. Results: The prepared nanocarriers had uniform particle
size distribution. The drug release rate was up to 80% within 48 h in the tumor environment. DOX/HA-ss-PSA NPs showed significant cytostatic effects. In addition, HA-ss-PSA NPs showed significant targeting and inhibition of cell migration in cell uptake and scratch assays. In vivoexperiments
showed that the prepared carriers had high tumor inhibition rates, good targeting effects on the liver and tumor, and significantly reduced toxicity to other tissues. Conclusion: The prepared HA-ss-PSA NPs could effectively inhibit the growth of HepG2 cells and tumors in vivo,
indicating that PSA could be used as a backbone component of a safe and reliable drug delivery system, providing a new strategy for the treatment of liver cancer.
研究领域:
药学
·
肿瘤学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF THE CHINESE CHEMICAL SOCIETY
·
2020
·Vol. 67
·期 5
·874-879
·
IF 1.554
Wenjie Li,Yan Lu,Yi Cheng,Hui Luo,Zhenbin Jia,Ning Li
Curcumol (Cur), which is the primary active anti-liver cancer component of Chinese traditional medicine Rhizoma zedoariae , was encapsulated in galactosylated liposomes to enhance its liver-targeting efficacy. In this study, we optimized the preparation methods, prescription, and process of galactosylated curcumol liposomes (Gal-Cur-L). The experimental results showed that the encapsulation efficiency, particle diameter, and stability coefficient of Gal-Cur-L obtained by the two-step emulsification method were improved compared with those of it obtained by other methods. Single-factor investigation showed that two factors, pH and the amount of triolein, contribute at least partly to the encapsulation efficiency and particle diameter of Gal-Cur-L. The best prescription and process were obtained through orthogonal test: the ratio of lecithin to cholesterol was 2:1, the ratio of drug to lipid was 1:2, and the amount of ether and Twain-80 were 4 ml and 1.6 g/L, respectively, 15 min for ultrasonic time, 100 W for ultrasonic power, and 20 min for homogeneous time. Using the best method, prescription, and process mentioned earlier, the basic test results of Gal-Cur-L were obtained, which demonstrated that our methods, prescription, and process of Gal-Cur-L were applicable. The encouraging results of this study provided references for the research of liver-targeting reagents of curcumol.
研究领域:
药剂学
·
肿瘤学
✓ 已验证
DOI
高影响因子
International Journal of Nanomedicine
·
2017
·
IF 4.3
Fang Yang,Xueyang Fang,Wenting Jiang,Tianfeng Chen
With many desirable features, such as being more effective and having multiple effects, antiangiogenesis has become one of the promising cancer treatments. The aim of this study was to design and synthesize a new targeted bioresponsive nanosystem with antiangiogenesis properties. The mUPR@Ru(POP) nanosystem was constructed by the polymerization of Ulva lactuca polysaccharide and N-isopropyl acrylamide, decorated with methoxy polyethylene glycol and Arg–Gly–Asp peptide, and encapsulated with anticancer complex [Ru(phen)2p-MOPIP](PF6)2·2H2O. The nanosystem was both pH responsive and targeted. Therefore, the cellular uptake of the drug was greatly improved. Moreover, the mUPR@Ru(POP) had strong suppressive effects against vascular endothelial growth factor (VEGF)-induced angiogenesis through apoptosis. The mUPR@Ru(POP) significantly inhibited VEGF-induced human umbilical vein endothelial cell migration, invasion, and tube formation. These findings have presented new insights into the development of antiangiogenesis drugs.
研究领域:
药学
·
肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
·
2022
·Vol. 110
·期 8
·1789-1795
·
IF 3.405
Xuan Chen,Shuting Lu,Fengrong Gong,Xiaoyu Sui,Tingting Liu,Ting Wang
Betulinic acid (BA), a natural pentacyclic lupine-type triterpene, has shown its prominent efficiency on the selective antitumor activity. However, its poor water solubility and bioavailability have limited its application. Herein, targeting nanoparticles were prepared to improve BA-based liposome (BL)'s restricted chemotherapeutic efficacy. Multi-layers membranes from the cancer cells were added as highly penetrative targeting ligands to functionalize the BA-based liposomes. In vitro experiments including the MTT assay and the fluorescence imaging of live/dead staining were adopted to prove its great inhibition in the growth of tumor cells. And it manifests that the antitumor efficacy of BL coated with cell membranes (BLCM) achieves nearly 4.3 times as that of BL under the same conditions in the MTT experiments. In addition, the fluorescence imaging stained with DAPI-FITC was applied to prove the targeting positioning effects on the BLCM. In a nutshell, the nanomedicine has good targeting antitumor efficacy and has great potential in being applied for the personalized cancer clinical treatment.
研究领域:
药理学
·
纳米医学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2018
·
IF 4.816
Liangfeng Huang,Gaofei Wei,Xiaoqi Sun,Yali Jiang,Zeqian Huang,Yanjuan Huang,Yifeng Shen,Xiaoyu Xu,Yunhui Liao,Chunshun Zhao
Therapeutic effects of photodynamic therapy (PDT) are limited by the selectivity of photosensitizer (PS). Herein, a novel tumor-targeted drug-PS conjugate (Gan-ZnPc) which integrated with zinc phthalocyanine (ZnPc) and Ganetespib has been developed. ZnPc is a promising PS with remarkable photosensitization ability. Ganetespib is a heat shock protein 90 (Hsp90) inhibitor with preferential tumor selectivity and conjugated to ZnPc as a tumor-targeted ligand. The multifunctional small molecule conjugate, Gan-ZnPc, could be bound to extracellular Hsp90 and then selectively internalized into the tumor cells, followed by the generation of abundant intracellular reactive oxygen species (ROS) upon irradiation. Besides, Gan-ZnPc can arrest cell proliferation and induce apoptosis by the inhibition of Hsp90. Herein, with combination of the inhibition of Hsp90 and the generation of cytotoxic ROS, Gan-ZnPc implements tumor selectivity, concentrated PDT and chemotherapy in a synergistic manner, which results in highly effective anti-tumor activity in vitro and in vivo.
研究领域:
药理学
·
肿瘤学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 103
·100984-100992
·
IF 3.289
Mengshi Yang,Di Jiang,Zhilong Chen,Jun Chen
Photodynamic therapy (PDT) does well in both curing early stage tumors and improving patients’ quality of life. However, the limited selectivity of photosensitizers (PSs) to tumors has become an urgent issue during the application of PDT clinically, which would exhibit a poor therapeutic outcome and induce skin phototoxicity. To solve this problem, PS-loaded D-α-tocopheryl polyethylene glycol succinate (vitamin E TPGS, or simply TPGS) nanoparticles with tumor homing and penetrating peptide tLyp-1 decoration (t-NP) were constructed for PDT of tumors in this study. Verteporfin (VP), as an effective PS, was encapsulated in the core of t-NP, and tLyp-1 was functionalized on the surface as a functional ligand to increase vascular permeability and target the tumor cells. These nanoparticles were spherical in shape and exhibited a narrow size distribution of 23.3 ± 0.80 nm, and had a high encapsulation efficiency and loading capacity of hydrophobic VP. Compared with unmodified nanoparticles (NP), t-NP exhibited enhanced cellular uptake in both primary human umbilical vein endothelial cells (HUVECs) and drug-resistant human colon adenocarcinoma cells (HCT15); and t-NP showed higher selectivity to HCT15 tumors in vivo after intravenous administration of the same dose of VP. The anti-tumor experiment in vivo strongly indicated that nanoparticles with tLyp-1 peptide modification can enhance the selectivity of the PS, and improve the PDT effect.
研究领域:
药剂学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
AAPS PHARMSCITECH
·
2016
·Vol. 18
·期 3
·729-737
·
IF 1.954
Li Yongquan,Xiao Yu,Yin Zongning
As an effective COX-2 inhibitor, celecoxib is widely used in anti-inflammation therapy. However, it may cause cardiovascular risks and renal adverse effects. In the present study, we aimed to construct a celecoxib prodrug with enhanced anti-inflammatory efficacy and reduced adverse effects using folate in order to target activated macrophages. Folate-glycine-celecoxib was synthesized and identified by 1 H-NMR, MS, and FTIR analyses. The cytotoxicity of folate-glycine-celecoxib was tested on murine macrophage cells (RAW264.7) using thiazolyl blue tetrazolium bromide. Cellular uptake studies were employed to determine targeting ability toward folate receptors via flow cytometry and confocal microscopy. Anti-inflammatory efficacy of folate-glycine-celecoxib was investigated by measuring the concentration of LPS-induced nitric oxide (NO). Folate-glycine-celecoxib exhibited lower cytotoxicity than conventional celecoxib, and this conjugate could be targetedly transported into RAW264.7 cells through binding with folate receptors on cell surface. Through targeting to RAW264.7 cells, folate-glycine-celecoxib exhibited better effects than equimolar celecoxib in NO inhibition, suggesting greater anti-inflammatory activity. These findings demonstrated that the prodrug folate-glycine-celecoxib had potential to treat inflammatory disease with low cytotoxicity and high targeting ability.
研究领域:
药理学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2018
·
IF 6.383
Jia Wen,Yinghua Lv,Yongqian Xu,Pengfei Zhang,Hongjuan Li,Xiaoxu Chen,Xueliang Li,Lingkai Zhang,Fengyu Liu,Wenxian Zeng,Shiguo Sun
A novel biodegradable versatile nanocarrier (FA-CM) was fabricated based on the self-assembly of delaminated CoAl-layered double hydroxides (LDHs) and manganese dioxide (MnO 2 ) for optional combination cancer therapy. Biodegradation, versatility, targeting, bioimaging, in vitro cytotoxicity and in vivo antitumor efficacy were evaluated. The results showed that FA-CM could not only be effectively degraded into Co 2+ , Al 3+ and Mn 2+ to overcome the long-term toxic side effects, but also successfully load any positive-charged, negative-charged, hydrophilic, and hydrophobic drug, meeting the critical requirement of versatile nanocarrier. Meanwhile, the presence of FA led to the higher uptake efficiency, cytotoxicity, and excellent fluorescence imaging of FA-CM toward cancerous cells. In particular, FA-CM exhibited glutathione and pH dual-response drug release, avoiding any premature leakage and side effects. The applicability of the FA-CM was determined by co-loading hydrophilic (doxorubicin (DOX)) and hydrophobic drug (paclitaxel (PTX)) for synergistic combination chemotherapy. In vitro cytotoxicity evaluation and a xenograft tumor model of hepatoma showed that this combination exhibited more efficient anticancer effects compared with either free drug alone or the corresponding cocktail solutions. Especially, the ratios of DOX and PTX loaded on FA-CM could be tuned as needed. A powerful approach is provided for the design and preparation of a biodegradable versatile nanocarrier with targeted ability and excellent biocompatibility, which can be potentially applied in clinical practice and medical imaging. Statement of Significance Drug delivery nanocarriers that can transport an effective dosage of drug molecules to targeted cells and tissues have been extensively designed to overcome the adverse side effects and low effectiveness of conventional chemotherapy. However, lack of biodegradability and versatility existing in majority of nanocarriers limit their further clinical applications. Thus, constructing a novel biodegradable versatile nanocarrier that can carry various types of drugs, is in urgent need and more suitable for commercial production and clinical use. In this study, we developed a novel biodegradable versatile nanocarrier (FA-CM) based on the self-assembly of delaminated CoAl-layered double hydroxides (LDHs) and manganese dioxide (MnO 2 ) for optional combination cancer therapy. This work provides a new strategy for constructing versatile biodegradable platform for targeted drug delivery, which would have broad applications in cancer theranostics.
研究领域:
药学
·
肿瘤学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Gaobing Ye,Shiyao Luo,Hajra Zafar,Honglei Ge,Binbin Liu,Nan Wang,Yu Jin,Miao Wang,Xu Chen,Xiaoming Ye
Esophageal cancer is one of the most common cancers in the world, ranking sixth in cancer-related mortality. Doxorubicin (DOX), as a classic broad-spectrum, non-specific small-molecular anti-tumor drug, has achieved widespread use, including in the treatment of esophageal cancer. However, due to its strong cardiotoxicity, poor tumor-targeting ability, and short half-life, the clinical application of DOX has been greatly limited. In this research, we designed and successfully synthesized a peptide sequence IEIIIK (IEK for short) with excellent pH responsiveness. Under physiological conditions (pH 7.4), the peptide can encapsulate DOX and self-assemble into a stable hydrogel (DOX-IEK) through hydrophobic and electrostatic interactions. After being injected into the acidic tumor microenvironment, the protonation degree of alkaline amino acid lysine increased and the negative charge of glutamate decreased, directly leading to enhanced electrostatic repulsion and subsequent hydrogel dissociation. Released DOX can accumulate in tumor tissue and achieve anti-tumor efficacy. More importantly, the hydrogel can act as a drug reservoir for sustained drug release, improving the drug targeting ability, prolonging the duration of drug administration to compensate for the short half-life of DOX, and reducing systemic toxicity. Ideal anti-tumor efficacy has been achieved in both the in vitro and in vivo experiments.
研究领域:
生物医学工程
·
药剂学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2016
·
IF 3.42
Xu Cheng,Xin Wang,Zhipeng Cao,Weijing Yao,Jun Wang,Rupei Tang
Soy protein isolate (SPI) was hydrolyzed by compound enzymes to give water soluble low molecular soy protein (SP). SP and folic acid (FA) modified SP was polymerized with N-3- acrylamidophenylboronic acid (APBA) monomer in aqueous solution to give SP nanoparticles (SP NPs) and FA modified nanoparticles (FA-SP NPs), respectively. These NPs display excellent stability in different conditions, and have a uniform spherical shape with a diameter around of 200 nm. Doxorubicin (DOX) was then successfully loaded into SP and FA-SP NPs with a desirable loading content of 13.33% and 16.01%, respectively. The cellular uptake and cytotoxicity of DOX-loaded SP NPs and FA-SP NPs were investigated using the two-dimensional (2D) monolayer cell model and three-dimensional (3D) multicellular spheroids (MCs). In vivo, tumor accumulation and growth inhibitory were then examined using H22 tumor-bearing mice. All these results demonstrated that conjugation of FA can efficiently enhance SP-based NPs' tumor accumulation and antitumor effect.
研究领域:
药剂学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanomedicine-Nanotechnology Biology and Medicine
·
2018
·
IF 6.5
Xinyu Wang,Zhi Chang,Xin Nie,Yingying Li,ZhenPeng Hu,Jinlong Ma,Wei Wang,Teng Song,Pei Zhou,Huaqing Wang,Zhi Yuan
The clinical translation remains a major challenge for platinum drug loaded nanoparticle due to the complexity of composition and preparation. Here we employed only three ingredients to prepare Pt (IV) prodrug-loaded ligand-induced self-assembled nanoparticles (GA-ALG@Pt NPs) via facile one-pot route for liver tumor treatment . GA-ALG@Pt NPs were found equipped with intelligently ligand self-shielded property in which the internal GA could be induced to expose by initial cellular recognition, resulting in strengthened cellular uptake (20%-30%) and prolonged blood circulation time (3.43 times). Appreciable tumor targeting ability (2 times) and especially tumor selectivity (2.5 times) were obtained. Glutathione-triggered release of therapeutic agent generated satisfactory antitumor effect. Bio-safety is also a distinguishing feature of GA-ALG@Pt NPs that greatly relief the nephrotoxicity and systematic toxicity of cisplatin . This conveniently synthesized nanoparticle processes superior targeting capacity and biosecurity, supplying an effective approach to translational cancer therapy in the future.
研究领域:
药学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2025
·
IF 5.4
Yibiao Zhou,Xiaowei Yang,Chao Deng,Yongjie Xia,Shengping Tang,Hongwu Zeng,Bin Zhang,Xiaoyong Zhang,Guibing Fu,Chao You
Osteoporosis (OP) is a degenerative bone disease that commonly occurs in elderly people. It often manifests in bone pain and increased risk of fractures, significantly impacting the quality of life for middle-aged and elderly individuals. Several anti-osteoporosis drugs are currently available in clinical practice, their long-term use has shown limited efficacy and potential complications. The natural compound puerarin (Pue) has demonstrated to be promising for OP treatment via regulating osteoclast and osteoblast differentiation. However, its poor solubility, low bioavailability, and lack of bone-targeting severely impeded its clinical applications. To address the above issues, we reported herein the synthesis of Pue-based framework (HCCP-Pue-PEG-ALN, HPPA NPs) via conjugation of Pue, NH 2 -PEG, and alendronic acid (ALN) using hexachlorocyclotriphosphazene (HCCP) as the linkage. We demonstrated that the HPPA NPs display the features, including high water dispersibility, pH responsive drug release, low cytotoxicity, bone targeting feature, and positive effects on both osteoclasts and osteoblasts. Therefore, we believe this idea reported in this work will be of great interest in design natural compounds-based drug delivery systems and promotes clinic translation of natural compounds for OP treatment.
研究领域:
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）