INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2025
·
IF 5.2
Xiaoyu Hu,Jun Liu,Qingrong Wang,Qiongkun Hu,Hao Sun,Shi Wang,Yu Zhao,Liwei Gu,Jianying Shen,Qinghe Zhao,Feng Sui,Hai Ma
Gemcitabine, a chemotherapeutic agent widely approved for treating various cancers, faces significant clinical challenges, including drug resistance and poor tumor selectivity. To address the limitation of inadequate tumor targeting, a peptide chain was developed to specifically bind to colon cancer cells and conjugated to gemcitabine via aldehyde–amine condensation. This study aimed to exploit the oncogenic activity of the multifunctional protein α-Enolase (ENO1). The therapeutic efficacy of gemcitabine conjugated with the ENO1-targeting peptide (GCB-P) was evaluated through in vitro and in vivo experiments. Cytotoxicity assays and protein blotting analyses were performed on cell lines, including NCM-460, HCT116 and SW620. GCB-P exhibited significantly enhanced selectivity and potency against colon cancer cells compared to gemcitabine alone, with minimal cytotoxicity to normal colorectal cells. In addition, GCB-P demonstrated superior tumor-selective accumulation and release at the tumor site, as evidenced by in vivo metabolic analyses. These findings underscore the potential of GCB-P as an effective colon cancer treatment with reduced off-target toxicity. Furthermore, GCB-P displayed acid-responsive properties, facilitating precise delivery to tumor sites with the aid of homing peptides. These results highlight the promise of ENO1-targeted peptide modification for gemcitabine in developing targeted drug delivery systems for colon cancer.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2020
·
IF 4.902
Renna Qiu,Denghua Sun,Yuzhuo Bai,Jiannan Li,Lizhe Wang
Osteosarcoma is the most common primary malignant bone tumor in childhood and adolescence. Currently, surgery combined with chemotherapy is the main treatment for osteosarcoma. However, the long-term survival of patients with metastatic osteosarcoma is unsatisfactory. Therefore, new treatment methods to improve the prognosis of patients with osteosarcoma are required. The present study aimed to develop nanocarriers with both tumor targeting and reduction responsiveness abilities, and to improve the therapeutic effect and reduce toxicity by loading traditional small molecule antitumor drugs. The tumor targeting peptide-decorated, doxorubicin (DOX)-loaded mPEG-P(Phe-co-Cys) nanoparticles were developed successfully through the ring-opening polymerization of amino acids. The peptide VATANST (STP) can specifically bind with vimentin, which is highly expressed on the osteosarcoma cell surface, resulting in tumor targeting effects. The nanoparticle is core–shell structured to protect the loaded DOX during blood flow. The disulfide bonds within the nanoparticles are sensitive to the osteosarcoma microenvironment, which has high glutathione (GSH) levels. Under the enhanced permeability and retention and active tumor targeting effects, the STP-decorated DOX-loaded nanoparticles accumulated in tumor tissues. High GSH levels can rupture disulfide bonds, resulting in the controlled release of DOX, which will cause necrosis of tumor cells. The characteristics of the synthesized nanoparticles, DOX release profiles in vitro and in vivo, cytotoxicity analysis, animal study, and safety evaluation were performed. The nanoparticles could increase the tumor inhibition efficiency against osteosarcoma and reduce the side effects of DOX to major organs. The STP-decorated mPEG-P(Phe-co-Cys) nanoparticles might be a suitable drug delivery system for DOX to treat osteosarcoma.
研究领域:
药学
·
肿瘤学
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生物材料学
✓ 已验证
DOI
PubMed
高影响因子
CHINESE CHEMICAL LETTERS
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2019
·
IF 3.839
Yanhui Sun,Aiyan Zhan,Shuang Zhou,Xiao Kuang,Hongyan Shen,Hongzhuo Liu,Youjun Xu
Mitochondrial dysfunction is associated with the emergence of several neurological and cardiovascular diseases. Hence, mitochondria-targeting delivery strategies are highly significant and critically needed. In this study, we developed a small library of peptides simulating the mitochondria-targeting peptide SS-31, a promising tetra-peptide with antioxidant character, and subsequently evaluated the toxicity, antioxidant ability and mitochondrial delivery of nanoparticles. Among the designed peptides, RF-2 ( d -Arg-Dmt-Arg-Phe-NH 2 ) showed controlled toxicity and excellent protection against gentamicin-induced hair cell damage, as compared with SS-31. More importantly, RF-2-modified PLGA nanoparticles demonstrated high colocalization with mitochondria and comparable specific subcellular accumulation, when compared with SS-31. Taken together, the obtained results supported RF-2 as a mitochondria-targeting peptide with high potential as a targeted carrier.
研究领域:
生物医学工程
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细胞生物学
·
药理学
✓ 已验证
DOI
高影响因子
MATERIALS & DESIGN
·
2024
·
IF 7.6
Li-chen Ji,Jia-qing Huang,Xu-gang Zhong,Qi-hong Sun,Yong Fan,Li Yin,Qiong Zhang,Yu Cai,Zeju He
Osteosarcoma, as the most prevalent primary malignant bone tumor, has consistently shown suboptimal clinical treatment outcomes. In this manuscript, we proposed an efficacious and novel phototherapy strategy for osteosarcoma based on a photoresponsive near-infrared (NIR) material, CaCO 3 -ICG-DDP-PEG-PT (CIDP-PT), which contained calcium carbonate (CaCO 3 ) and Cisplatin (DDP) via the gas dispersion method, and indocyanine green (ICG) was encapsulated through a nanoprecipitation reaction by employing DSPE-PEG 2000 -COOH to enhance the stability and hydrophilicity. The targeting oligopeptide (PT) for osteosarcoma cells was inserted into the outer membrane of nanoparticles, thereby further enhancing the tumor-targeting capability through receptor-mediated binding. The prepared CIDP-PT nanoparticles exhibited high targeting efficiency and multifunctionality. In vitro and in vivo experiments demonstrated that CIDP-PT significantly enhanced the therapeutic efficacy for osteosarcoma via the NIR-II photoresponsive and tumor-targeting approach. It achieves efficient tumor cell eradication through multiple modalities while maintaining an exceptional level of biocompatibility. Hence, the CIDP-PT nanocarriers possess considerable practical value for future clinical applications in adjunct osteosarcoma phototherapy.
研究领域:
肿瘤学
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纳米医学
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生物材料学
✓ 已验证
产品关联
DOI
高影响因子
Small
·
2013
·Vol. 9
·期 24
·4183-4193
·
IF 7.823
Ming-Zhen Zhang,Yong Yu,Rong-Na Yu,Min Wan,Rong-Ying Zhang,Yuan-Di Zhao
Based on the multivalent binding capability of streptavidin (SA) to biotin, a multifunctional quantum dot probe (QD-(AS-ODN+p160)) coupled with antisense oligonucleotide (AS-ODN) and peptide p160 is designed for real-time tracking of targeted delivery of AS-ODN and regulation of folate receptor-α (hFR-α) in MCF-7 breast cancer cells. Fluorescence spectra, capillary electrophoresis (CE) and dynamic light scattering (DLS) are used to characterize the conjugation of AS-ODN and p160 with quantum dots (QDs), DLS results confirm the well stability of the probe in aqueous media. Confocal imaging and quantitative flow cytometry show that QD-(AS-ODN+p160) is able to specifically target human breast cancer MCF-7 cells. Low temperature and ATP depletion treatments reveal the cellular uptake of QD-(AS-ODN+p160) is energy-dependent, and the effects of inhibition agents and co-localization imaging further confirm the endocytic pathway is mainly receptor-mediated. Transmission electron microscopy (TEM) shows the intracellular delivery and endosomal escape of QD probe along with incubation time extended. Two transfection concentrations of QD probe (10 nM and 50 nM) below half inhibitory concentration (IC 50 ) value are chosen according to MTT assay. Real-time PCR shows at these two concentration cases the relative mRNA expression levels of hFR-α reduce to 72.5 ± 3.9% and 17.6 ± 1.0%, respectively. However, western blot and quantitative ELISA analysis show the expression level of hFR-α protein has a significant decrease only at 50 nM, indicating that gene silence is concentration-dependent. These results demonstrate that the QD-(AS-ODN+p160) probe not only achieves gene silence in a cell-specific manner but also achieves real-time tracking during AS-ODN intracellular delivery.
研究领域:
分子生物学
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癌症研究
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
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2017
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IF 4.162
Linge Nian,Yue Hu,Caihong Fu,Chen Song,Jie Wang,Jianxi Xiao
The development of novel assays to detect collagen fragments is of utmost importance for diagnostic, prognostic and therapeutic decisions in various collagen-related diseases, and one essential question is to discover probe peptides that can specifically recognize target collagen sequences. Herein we have developed the fluorescence self-quenching assay as a convenient tool to screen the capability of a series of fluorescent probe peptides of variable lengths to bind with target collagen peptides. We have revealed that the targeting ability of probe peptides is length-dependent, and have discovered a relatively short probe peptide FAM-G(POG) 8 capable to identify the target peptide. We have further demonstrated that fluorescence self-quenching assay together with this short probe peptide can be applied to specifically detect the desired collagen fragment in complex biological media. Fluorescence self-quenching assay provides a powerful new tool to discover effective peptides for the recognition of collagen biomarkers, and it may have great potential to identify probe peptides for various protein biomarkers involved in pathological conditions.
研究领域:
生物化学
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分子生物学
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诊断学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
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2025
·
IF 26.8
Yuqiong Xia,Zhaoxu Chen,Xianghan Zhang,Peng Yang,Zhongliang Wang
Thrombotic cardiovascular diseases remain the leading cause of mortality worldwide. However, current thrombolytic therapeutics suffer from limited efficacy and a high risk of severe bleeding. Here, a phosphatidylcholine liposome accelerated platinum nanomachine (PLANE) for thrombus mechanotherapy is designed, constructed by encapsulating platinum nanomotors within isotropic, lubricating phosphatidylcholine (PC) liposomes. The precisely engineered PLANE exhibits superior lubricity and linear motion. Under laser irradiation and hydrogen peroxide treatment, PLANEs achieve significantly higher velocities than conventional platinum nanomotors, facilitating deep penetration into the thrombi. Further functionalization with thrombus-targeting peptides enables the cPLANEs to selectively accumulate at the thrombotic sites in vivo, demonstrating excellent thrombolytic efficacy. This work presents a novel surface modification strategy for optimizing the motion behavior of platinum nanomotors, offering a promising non-pharmaceutic approach for thrombotic disease treatment.
研究领域:
纳米医学
·
生物材料
·
心血管疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2021
·
IF 7.991
Kunyu Zhang,Zhong Wan,Huabo Jiang,Xiufeng Xiao,Qian Feng,Yanchun Meng,Yongsheng Yu
Breast cancer is one of the leading causes of cancer-related deaths in women. Chemotherapy remains one of the main clinical treatments for breast cancer. However, this therapy has appreciable side effects. Nanoscale carriers, such as metal nanoparticles and liposomes, are being widely utilized as drug delivery vehicles to achieve precise targeting of tumor cells. In this study, we designed a novel upconversion nanocarriers (UCNCs) host-guest complexation system based on a photolabile capping-like molecule. UCNCs containing epirubicin (EPI) were grafted with a dimer-targeting peptide via cyclodextrin-adamantine host-guest complexation. After entering breast tumor cells with the guidance of the dimer-targeting peptide, the core of the UCNCs upconverted near-infrared light to ultraviolet light which subsequently triggered the intracellular on-demand release of epirubicin. The precise and efficient delivery and release of epirubicin inside breast cancer cells significantly inhibited cancer cells proliferation, migration, and invasion in vitro and decreased the tumor size in vivo . We believe that this UCNCs system is a promising platform for the precise and controllable delivery of various chemotherapy drugs for clinical cancer treatments.
研究领域:
肿瘤学
·
药剂学
·
纳米医学
✓ 已验证
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2016
·
IF 3.902
Yin-Jia Cheng,Xuan Zeng,Dong-Bing Cheng,Xiao-Ding Xu,Xian-Zheng Zhang,Ren-Xi Zhuo,Feng He
Synergistic therapy involving two or more therapeutic agents with different anticancer mechanisms represents a promising approach to eradicate chemotherapy-refractory cancers. However, the preparation of a synergistic therapy platform generally involves complicated procedures to encapsulate different therapeutic agents and thereby increases the purification difficulty. In this work, we reported a simple but robust strategy to prepare a highly controllable drug delivery system (DDS) for synergistic cancer therapy. To construct this robust DDS, mesoporous silica nanoparticles (MSNs) were employed as a nanoplatform to encapsulate anticancer drug doxorubicin (DOX). After using a tumor-targeting cellular membrane-penetrating peptide (TCPP) and a mitochondria-targeting therapeutic peptide (TPP) to seal the surface pores via disulfide bonds, these newly developed MSNs can target cancer cells, penetrate cell membrane and rapidly release anticancer drug and mitochondria-targeted peptide in cytoplasm, inducing a remarkable synergistic anticancer effect. The new design concept reported here will promote the development of targeted and smart DDSs for synergistic cancer therapy.
研究领域:
生物医学工程
·
癌症治疗
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Chemistry
·
2022
·
IF 5.545
You Lijiao,Wang Qing,Ma Yuhui,Li Yunfeng,Ye Hui,Xu Lingli,Lei Ming
Myocardial infarction (MI) may cause irreversible damage or destroy to part of the heart muscle, affecting the heart’s ability and power to pump blood as efficiently as before, often resulting in heart failure (HF). Cardiomyocyte death and scar formation after MI may then trigger chronic neurohormonal activation and ventricular remodeling. We developed a biocompatible and mono-dispersed mesoporous silica nanoparticles (MSN) divergent porous channel for dapagliflozin (DAPA) loading. After surface modification of the cardiac-targeting peptides, the novel drug delivery system was successfully homed, and precisely released drugs for the hypoxic and weak acid damaged cardiomyocytes. Our biocompatible MSN- based nanocarriers for dapagliflozin delivery system could effective cardiac repair and regeneration in vivo, opening new opportunities for healing patients with ischemic heart disease in clinical.
研究领域:
药剂学
·
心血管医学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2016
·
IF 3.902
Yan Jiang,Lingyan Lv,Huihui Shi,Yabing Hua,Wei Lv,Xiuzhen Wang,Hongliang Xin,Qunwei Xu
Glioblastoma multiforme (GBM) is the most common and aggressive primary central nervous system (CNS) tumor with a short survival time. The failure of chemotherapy is ascribed to the low transport of chemotherapeutics across the Blood Brain Tumor Barrier (BBTB) and poor penetration into tumor tissue. In order to overcome the two barriers, small nanoparticles with active targeted capability are urgently needed for GBM drug delivery. In this study, we proposed PEGylated Polyamidoamine (PAMAM) dendrimer nanoparticles conjugated with glioma homing peptides (Pep-1) as potential glioma targeting delivery system (Pep-PEG-PAMAM), where PEGylated PAMAM dendrimer nanoparticle was utilized as carrier due to its small size and perfect penetration into tumor and Pep-1 was used to overcome BBTB via interleukin 13 receptor α2 (IL-13Rα2) mediated endocytosis. The preliminary availability and safety of Pep-PEG-PAMAM as a nanocarrier for glioma was evaluated. In vitro results indicated that a significantly higher amount of Pep-PEG-PAMAM was endocytosed by U87 MG cells. In vivo fluorescence imaging of U87MG tumor-bearing mice confirmed that the fluorescence intensity at glioma site of targeted group was 2.02 folds higher than that of untargeted group (**p < 0.01), and glioma distribution experiment further revealed that Pep-PEG-PAMAM exhibited a significantly enhanced accumulation and improved penetration at tumor site. In conclusion, Pep-1 modified PAMAM was a promising nanocarrier for targeted delivery of brain glioma.
研究领域:
医学
·
药学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Biomedical Engineering
·
2020
·Vol. 4
·期 7
·732-742
·
IF 18.952
Li Suping,Zhang Yinlong,Ho Shih-Hsin,Li Bozhao,Wang Meifang,Deng Xiongwei,Yang Na,Liu Guangna,Lu Zefang,Xu Junchao,Shi Quanwei,Han Jing-Yan,Zhang Lirong,Wu Yan,Zhao Yuliang,Nie Guangjun
Drugs that induce thrombosis in the tumour vasculature have not resulted in long-term tumour eradication owing to tumour regrowth from tissue in the surviving rim of the tumour, where tumour cells can derive nutrients from adjacent non-tumoral blood vessels and tissues. Here, we report the performance of a combination of tumour-infarction therapy and chemotherapy, delivered via chitosan-based nanoparticles decorated with a tumour-homing peptide targeting fibrin–fibronectin complexes overexpressed on tumour-vessel walls and in tumour stroma, and encapsulating the coagulation-inducing protease thrombin and the chemotherapeutic doxorubicin. Systemic administration of the nanoparticles into mice and rabbits bearing subcutaneous or orthotopic tumours resulted in higher tumour growth suppression and decreased tumour recurrence than nanoparticles delivering only thrombin or doxorubicin, with histological and haematological analyses indicating an absence of detectable toxicity. The co-administration of a cytotoxic payload and a protease to elicit vascular infarction in tumours with biodegradable tumour-targeted nanoparticles represents a promising strategy for improving the therapeutic index of coagulation-based tumour therapy.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）