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
RSC Advances
·
2016
·Vol. 6
·期 48
·42109-42119
·
IF 3.289
Gang Pan,Yi-jie Bao,Jie Xu,Tao Liu,Cheng Liu,Yan-yan Qiu,Xiao-jing Shi,Hui Yu,Ting-ting Jia,Xia Yuan,Ze-ting Yuan,Pei-hao Yin,Yi-jun Cao
We report on the fabrication of a multifunctional polymeric prodrug covalently linked with an anticancer drug (bufalin, BUF) and tumor-targeting peptide (RGD) and investigate its anticancer performance against colon cancer in mice. The polymerizable monomer, 3-((2-(methacryloyloxy)ethyl) thio)propanoic acid (BSMA), was synthesized first. Atom radical transfer polymerization (ATRP) of BSMA and oligo(ethylene glycol) monomethyl ether methacrylate (OEGMA) afforded random copolymers, P(OEGMA-co-BSMA). The polymeric prodrug of BUF, P(OEGMA-co-BUF), was obtained by an esterification reaction between the carboxyl groups of P(OEGMA-co-BSMA) and the hydroxyl group of BUF. Finally, a tumor-targeting polymeric prodrug, P(OEGMA-co-BUF-co-RGD), was obtained via an aminolysis reaction of P(OEGMA-co-BUF) in the presence of RGD and the final drug content was determined to be ∼32.9 wt%. In aqueous media, P(OEGMA-co-BUF-co-RGD) self-assembles into micelles and the hydrodynamic diameter (Dh) of the micelles was determined to be ∼33.0 (±2.5) nm by dynamic laser light scattering (LLS). It was demonstrated that the tumor-targeting polymeric prodrug showed improved anticancer performance both in vitro and in vivo in comparison with that of free BUF.
研究领域:
药学
·
肿瘤学
·
生物材料
✓ 已验证
产品关联
DOI
高影响因子
RSC Advances
·
2014
·Vol. 4
·期 106
·61948-61959
·
IF 3.708
Manhong Tan,Jia Luo,Ying Tian
As gemcitabine and curcumin have different targets in colon cancer cells, combination of them may bring benefits. Here, curcumin and gemcitabine were formulated into a biodegradable polymer platform for combination therapy for treatment of colon cancer. In doing so, a FDA approved biodegradable polymer mPEG-PLA (methoxyl-polyethylen glycol-block-polylactide) was chosen as a drug carrier. At first, a mPEG-PLA/Gem conjugate was designed. Thereafter, simply using this drug conjugate to encapsulate curcumin, polymeric micelles loaded with both curcumin and gemcitabine were obtained. Varying the feed ratio of the two drugs, a series of micelles with different ratios of curcumin and gemcitabine could be prepared. The as-prepared dual drug loaded nanoparticles showed spherical structures with mean diameters ranging from 118 nm to 149 nm by DLS. In vitro, M(Cur/Gem) almost showed greater synergy than free combination of curcumin/gemcitabine. In vivo, better antitumor effect and lower systemic toxicity of M(Cur/Gem) were observed on a murine xenograft model. The present study provides the possibility of combining curcumin and gemcitabine in a nanoparticle formulation, and translation of this combination may bring benefits for future clinical use.
研究领域:
药剂学
·
肿瘤学
✓ 已验证
DOI
高影响因子
CARBOHYDRATE RESEARCH
·
2014
·
IF 1.966
Rui-jian Jiang,Yu-lin Zhao,Yun-jian Chen,Dan Xiao,Fen Wang,Bin Han,Jian Yang,Xia-li Liao,Li-Juan Yang,Chuan-zhu Gao,Bo Yang
A novel series of artesunate-β-cyclodextrin (ATS-β-CD) conjugates, in which artesunate (ATS) was coupled covalently to one of the primary hydroxyl groups of β-cyclodextrin (β-CD) through amino bond formation, were synthesized and characterized by 1 H NMR, HRMS, 2D NMR (ROESY), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The results showed that the aqueous solubility of ATS-β-CD conjugates was 26–45 times better than that of free ATS. The cytotoxicity of the ATS-β-CD conjugates was evaluated on human colon cancer cell lines HCT116, LOVO, SW480, and HT-29, and the results indicated that ATS-2NβCD exhibited a very high cytotoxicity against HCT116, LOVO, and HT-29 with IC 50 values of 0.58, 1.62, and 5.18 μmol/L, respectively. In addition, the supposition of better cytotoxicity was further supported by the control experiment of fluorescent cyclodextrin .
研究领域:
药物化学
·
肿瘤学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Ya-Hui Yu,Kouadio Jean Eric-Parfait Kouame,Xiaozhen Liu,Xiangying Yu,Ming-Yu Jin,Long-Qing Li,Fengyuan Liu,Yuting Li,Jing-Kun Yan,Bing Li
The combination of selenium nanoparticles (SeNPs) with natural polysaccharides represents an effective strategy to address the limitations of SeNPs and providing a stable, highly bioactive form of Se. In this study, we explored the potential of longan polysaccharides (LP) in the preparation and stabilization of SeNPs. The morphology, stability, stabilization mechanism, and cytotoxicity of LP-SeNPs were investigated. The results showed that the LP-SeNPs were uniform spherical nanoparticles with a mean particle size of 100.4 ± 1.1 nm, and demonstrated excellent stability over a 14-day storage period, which was attributed to the interaction between the SeNPs and the hydroxyl groups present on the surface of LP. Meanwhile, LP-SeNPs have no toxic effect on rat intestinal epithelial (IEC-6) cells, while they are cytotoxic to human colon cancer (HCT-116 and HT-29) cells, including growth inhibition, morphological alteration, and the promotion of reactive oxygen species and mitochondrial membrane potential loss in a dose-dependent manner. LP-SeNPs induced apoptosis in HCT-116 and HT-29 cells by regulation of the apoptosis-related proteins including Bax, Bcl-2, caspase-3, and cytochrome c . Therefore, our results provide a theoretical basis for the development and application of LP and indicate the potential promise of LP-SeNPs as dietary Se supplements and health-promoting food ingredients.
研究领域:
食品科学
·
生物医学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Heliyon
·
2022
·
IF 3.776
Xiaotao Qian,Yongxin Zhao,Tengyue Zhang,Pingsheng Fan
The aim of this study is to investigate the reversal effect of verapamil (VER) on chemoresistance to irinotecan (CPT-11) in human colon cancer cells and relevant mechanisms. Cell counting kit-8 (CCK-8) test and colony-forming unit (CFU) experiment results show that VER strengthens the sensitivity of human colon cancer cell line HT29 to CPT-11 but has a small effect on SW480 cells. High-throughput transcriptome sequencing, RT-PCR, and Western blot results show that the inhibition of metastasis-associated in colon cancer-1 (MACC1) expression by VER is the key factor for reversal effect on chemoresistance to CPT-11. Transfection experiments further show that VER can reverse the resistance of human colon cancer cells to SN-38, the active metabolite of CPT-11, when MACC1 is overexpressed. The nude mouse transplantation tumor experiment provides an in vivo proof that VER can strengthen sensitivity to CPT-11 in drug-resistant human colon cancer cells, and the effect might be related to the inhibited expression of MACC1. In summary, VER might strengthen the reversal effect of VER on chemoresistance to CPT-11 in human colon cancer cells and facilitate the apoptosis of human colon cancer cells by downregulating MACC1 expression.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2021
·
IF 5.89
Xie Dengchao,Ma Panpan,Ding Xin,Yang Xiao,Duan Lian,Xiao Bo,Yi Shixiong
Colon cancer ranks as the third most common malignancy in the world. Combination chemotherapy, resorting to electrospun fibrous technology, has been considered as a promising strategy to exert synergistic effects in colon cancer treatment. Herein, we manufactured various pluronic F127 (PF127)-modified electrospun fibrous meshes with different weight ratios of camptothecin (CPT) and curcumin (CUR). The fluorescence characterization of the obtained PF127-CPT-meshes, PF127-CUR-meshes, and PF127-CPT/CUR-meshes (2:1) showed that CPT and CUR were evenly distributed within individual fibers of these meshes. Drug release experiments revealed that both types of drugs could be released from fibrous meshes simultaneously and sustainably. Importantly, these meshes exhibited strong in vitro anti-colon cancer activities, compared with the control meshes without drugs. Moreover, the combination index values of the PF127-CPT/CUR-meshes (CPT/CUR weight ratio = 5:1, 3:1, or 2:1) were <0.5 after incubation for respective 24 and 36 h, indicating the synergistic anti-colon cancer effects of CPT and CUR in fibrous meshes. Collectively, these results demonstrate that PF127-CPT/CUR-meshes can be developed as an efficient implantable system for effective synergistic treatment of colon cancer.
研究领域:
肿瘤学
·
药剂学
·
生物材料学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Guodong Ren,Xuewei Wang,Jianbo Cao,Haolin Pu,Jinyao Li,Lili Yan,Sufang Ma,Lihong Li,Lixia Guo,Boye Zhang,Haojiang Wang,Bin Wang,Haipeng Diao,Wen Liu,Chengwu Zhang
Colon cancer is one kind of malignant digestive tract tumor with high morbidity and mortality worldwide, treatments for which still face great challenges. Recently emerged intervention strategies such as phototherapy and gas therapy have displayed promising effects in the treatment of colon cancer, but their application are still hindered due to insufficient tumor targeting and deeper tissue penetrating capacity. Herein, in the present study, we developed one theranostic nanoplatform Cet-CDs-SNO (CCS) to realize multimodal imaging-guided synergistic colon cancer therapy. Among the CCS, Cetuximab (Cet), one first-line clinical drugs for colorectal cancer, endowed CCS with tumor-targeting capacity and enhanced drug accumulation in tumor cells; CDs doped by Ni2+ and Mn2+ served as NIR-II photothermal therapy (PTT), chemodynamic therapy (CDT), and photothermal/magnetic resonance/fluorescence imaging (PTI/MRI/FLI) agents; SNO, a nitric oxide (NO) donor, exerted gas therapeutic (GT) effects under thermal stimulation derived from PTT. In vitro and in vivo experiments proved that CCS had excellent colon cancer-targeting ability. Proliferation of colon cancer cells and tumor growth were significantly inhibited by the administration of CCS without detectable cytotoxicity. This study presented one strategy for developing a multifunctional nanoplatform to be applied in imaging-guided precise tumor therapy.
研究领域:
肿瘤学
·
纳米医学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-20
·
IF 12.6
Wu Can,Zhang Xiao Wei,Wang Manman,Sun Jinpan,Chen Jianfei,Guan Yanbin,Pang Xin
Chemotherapy remains an effective treatment for colon cancer but is hampered by its limited response rate. Bioactive peptides, marked with intracellular transformations, have been reported as an effective approach to boosting chemotherapeutic activity. Herein, a promising trypsin-responsive bioactive peptide-based nanodrug is constructed, which could significantly prolong the drug retention time in vivo by cascading transformations and improve chemotherapeutic efficacy. Initially, 1-Pept co-assembles with Dox into a few nanofibers called 1-Pept/Dox NFs, inducing an enhanced cellular uptake via caveolae-mediated endocytosis by avoiding lysosomal degradation and further promoting perinuclear transportation, thus enlarging the drug efficacy in target areas. After nanofiber disassembly, the released 1-Pept converts into Pept under the catalysis of intracellular overexpressed trypsin, which then reassembles into denser Pept NFs, inducing a cascade of effects including disruption of the cytoskeleton, mitochondrial dysfunction, and activation of caspase-3. By the synergism of Pept NFs and Dox, caspase-3 can be further activated, and cause greater damage to nuclear, thereby leading to tumor ablation. As the first example of employing trypsin-mediated nanodrugs with cascading transformations to promote chemotherapeutic activity, this work promises a strategy for novel therapies for efficiently combating colon cancer. Graphical
研究领域:
药理学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Qiao Qiao,Jie Li,Chunying Tao,Meiyang Yang,Weijun Chen,Lipeng Qiu,Huiming Tu
Studies have shown that inflammation is closely linked to the cancer development, and the patients with inflammatory bowel disease (IBD) have a higher risk of colon cancer. Celecoxib (CXB) and camptothecin (CPT) showed potential treatment for IBD and colon cancers, respectively. However, their applications are limited by synchronous delivery, water insolubility, and off-target side effects. Herein, a glutathione (GSH) responsive chondroitin sulfate A (CSA)-SS-CXB micelle loaded with CPT (CSA-SS-CXB@CPT) was prepared as a targeted system to treat colon cancer by anti-inflammatory and antitumor synergistic effect. Specifically, CSA had tumor tumor-targeting effect due to colon cancer lesion-high expression of CD44 receptors. In vitro results verified that CSA-SS-CXB@CPT selectively internalized into colon cancer HT-29 cells and had strong reactive oxygen species (ROS) elimination ability. The CSA-SS-CXB@CPT could rapidly release CXB and CPT in the tumor microenvironment for playing an anti-tumor role. In vivo experiments illustrated that CSA-SS-CXB@CPT significantly targeted tumor tissues and suppressed tumor growth without producing serious side effects in tumor-bearing nude mice. Therefore, this work provides an opportunity for targeted co-delivery of anti-inflammatory and chemotherapy drugs to treat colon cancer.
研究领域:
药学
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Kexin Cui,Zhang Fangming,Tianzi Shi,Siyu Zhao,Yixuan Zhou,Xiong Liu,Yong Hu,Zhaoyu Hu,Li Kong,Zhiping Zhang
Ionizable lipids are crucial for the effective delivery of mRNA by using lipid nanoparticles (LNPs). Endowing ionizable lipids with tailored biological properties could potentially augment the therapeutic efficacy of mRNA-based treatments. Herein, a functional vitamin E (VE)-based lipid library with distinct head groups was designed and synthesized. Due to the presence of VE, these lipids inherently exhibited immunomodulatory properties, including the promotion of cellular uptake, dendritic cells maturation, and antigen presentation. Through iterative optimization of the LNP components and the architecture of ionizable lipids, the correlation between the structure of ionizable lipids and their mRNA delivery efficiency has been established, leading to the finding of the most effective delivery formulation. Benefiting from the high mRNA delivery efficiency and the immunomodulatory function of LNPs themselves, VE-based LNPs have demonstrated complete remission in colon cancer by delivering mIL-12, which offered a beneficial combination with immune checkpoint blockade. The proposed functional LNPs were anticipated to furnish potential delivery systems for mRNA-based cancer treatments.
研究领域:
生物技术
·
肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR BIOCHEMISTRY
·
2024
·Vol. 479
·期 7
·1747-1766
·
IF 3.5
Wang Qun,Lu Weijun,Lu Li,Wu Ruopu,Wu Dongde
Receptor interacting protein serine/threonine kinase 4 (RIPK4) is widely involved in human cancer development. Nevertheless, its role in colon cancer (COAD) has not been elucidated till now. Our research aimed at exploring the function and underlying molecular mechanism of RIPK4 in COAD progression. Through bioinformatic analyses and RT-qPCR, RIPK4 was discovered to be increased in COAD cells and tissues, and its high level predicted poor prognosis. Loss-of-function assays revealed that RIPK4 silencing suppressed COAD cell growth, induced cell cycle arrest, and enhanced cell apoptosis. In vivo experiments also proved that tumor growth was inhibited by silencing of RIPK4. Luciferase reporter assay validated that RIPK4 was targeted and negatively regulated by miR-575. Western blotting demonstrated that Wnt3a, phosphorylated (p)-GSK-3β, and cytoplasmic and nuclear β-catenin protein levels, β-catenin nuclear translocation, and Cyclin D1, CDK4, Cyclin E, and c-Myc protein levels were reduced by RIPK4 knockdown, which however was reversed by treatment with LiCl, the Wnt/β-catenin pathway activator. LiCl also offset the influence of RIPK4 knockdown on COAD cell growth, cell cycle process, and apoptosis. Finally, RIPK4 downregulation reduced RUNX1 level, which was upregulated in COAD and its high level predicted poor prognosis. RIPK4 is positively associated with RUNX1 in COAD. Overexpressing RUNX1 antagonized the suppression of RIPK4 knockdown on RUNX1, Wnt3a, p-GSK-3β, cytoplasmic β-catenin, nuclear β-catenin, Cyclin D1, CDK4, Cyclin E, and c-Myc levels. Collectively, miR-575/RIPK4 axis repressed COAD progression via inactivating the Wnt/β-catenin pathway through downregulating RUNX1.
研究领域:
肿瘤学
·
分子生物学
·
生物信息学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）