RSC Advances
·
2017
·Vol. 7
·期 41
·25694-25701
·
IF 3.108
Xiaoju Shi,Guoyue Lv,Xiaodong Sun,Dianbo Cao,Guangyi Wang,Yulei Chang
Recently, several targeted drug delivery systems have shown promising antitumor activity towards different types of cancer. However, targeting the tumor microenvironment, cellular surface and/or only one organelle may not achieve the expected therapeutic effects. Herein, a targeted drug delivery with stepwise targeting and image-guided strategy was obtained for enhancing antitumor therapy and overcoming various problems caused by the random drug distribution of traditional medicine. In this design, a multifunctional nanoplatform, TPGS/PPG2L@IONPs@DOX/TPP–DOX, based on poly(ethylene glycol)-poly(ε-caprolactone)-poly(amidoamine)-lactose acid (mPEG-PCL-G2.0 PAMAM-LA, PPG2L) copolymer and D-α-tocopherol polyethylene glycol 1000 succinate (TPGS), as a co-carrier, incorporates iron oxide nanoparticles (IONPs) as imaging agents and loads a DOX/triphenylphosphonium (TPP)–DOX drug for chemotherapy. In this nanoplatform micelle, the LA as targeting moieties to hepatocarcinoma cells is the first targeting step. After the drug is released from the hybrid micelles, the incorporated DOX and TPP–DOX target delivery to nuclei and mitochondria for the next targeting step. Furthermore, with the help of MRI contrast agents of IONPs, the distribution of hybrid micelles was monitored. As a result, the hybrid micelles demonstrated enhanced antitumor cell activity in both HepG2 and HepG2/DOX cells. The results indicated that the multifunctional hybrid micelles showed great potential in enhancing antitumor activity under image-guided and stepwise targeted chemotherapy.
研究领域:
药学
·
癌症研究
·
纳米技术
·
医学影像
✓ 已验证
产品关联
DOI
高影响因子
Scientific Reports
·
2025
·Vol. 15
·期 1
·1-12
·
IF 3.9
Li Silong,Li Na,Yin Qiangqiang,Zhang Zhichen,Hu Haifeng,Hao Liguo
This project aims to construct cRGD functionalized mesoporous silica nanoparticles and cRGD modified mesoporous silica nanoparticles for the diagnosis and treatment of tumors, providing new ideas for targeted therapy of tumors. The mesoporous silica nanoparticles were doped with gadolinium in situ to provide excellent imaging; cRGD was coupled on the particle surface to confer particle targeting; and hyaluronic acid was loaded onto the particles by electrostatic adsorption, thereby improving the biocompatibility of the particles and prolonging their in vivo circulation time.Taking pancreatic cancer as a model, we studied its targeting ability to pancreatic cancer and its phagocytosis to cancer cells; Using methods such as cell growth experiments and flow cytometry, the anti-cancer effect and pro apoptotic effect of the system were studied. In vivo distribution, tumor targeting and therapeutic efficacy of nanoparticles evaluated in a mouse model of pancreatic cancer with loaded tumors.Evaluate the bioavailability and enrichment of nanoparticles in tumor tissue using MRI technology. Evaluate the therapeutic effect and safety through changes in tumor volume, histopathological examination, and prognosis. Characterization of the synthesis results proved that cRGD-HA-DOX-Gd 2 O 3 @MSN (cHDG@MSN) was successfully synthesized with a particle size of 230.83 ± 12.36 nm.In vitro drug release experiments of DOX were carried out at different pH values (5.5 and 7.4), where the release was only up to 22.65% at pH 7.4, whereas DOX release was increased up to 78.75% at pH = 5.5.The results confirm the pH responsiveness of this nanocarrier platform.The results of cytotoxicity studies showed that cHDG@MSN itself is not cytotoxic. Biosafety evaluation and hemolysis test results confirmed that the probe is highly biocompatible.Notably, Gd 3+ significantly enhanced the T 1 contrast of the system according to MR imaging results.The apoptosis rates of SW1990 cells treated with PBS, DOX and cHDG@MSN in flow cytometry were 13.97%, 18.38% and 29.02%, respectively, demonstrating the effectiveness of the nanoprobes at the cellular level. Animal experiments demonstrated the effectiveness of nanoprobes at the pathological level and imaging level.Cells and animals demonstrated that cHDG@MSN effectively inhibited the proliferation of pancreatic cancer cells. This research further verified the pH sensitivity of the constructed compound drug delivery system to achieve accurate diagnosis and treatment of pancreatic cancer tumor cells.
研究领域:
肿瘤学
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纳米医学
·
影像医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Huixin Wang,Wenshen Wang,Chengpan Li,Ao Xu,Bensheng Qiu,Fenfen Li,Weiping Ding
Microneedles (MNs) are an attractive strategy for the efficient, painless transdermal delivery of drugs with low systemic toxicity. In this work, a novel near-infrared (NIR) light-triggered separable microneedle system was fabricated to supply controlled chemo-thermal therapy to superficial tumors by co-loading a self-developed NIR-II fluorescence fluorophore Flav7 and the antitumor drug doxorubicin (DOX) in phase-change polycaprolactone (PCL) arrowheads on a soluble base. For the MNs we proposed, Flav7 offers MNs with NIR light-triggered heating generation and drug release properties as well as a NIR-II imaging ability for guiding combined chemo-thermal therapy, and the soluble supporting base ensures that the needle arrows are embedded in the skin after insertion and endows the MNs with a separation ability to reduce the contact time of the MNs with the skin. In vitro studies showed that Flav7 + DOX-loaded MNs exhibited adequate insertion abilities, stable thermal properties, and desirable light-activated melting effects and drug release capabilities. In vivo studies showed that the Flav7 + DOX-loaded MNs presented a remarkable NIR-II imaging ability, a good biosafety to the major organs, and a strong tumor-killing ability. It is worth noting that all of the treated breast cancer mice survived for 50 days without tumor recurrences or major organ damage. This study presented a promising MN system loaded with the multipurpose small molecule Flav7 that can be used for high-efficiency light-activated drug release for chemotherapy and high-performance light-controlled thermotherapy of tumors and also for remarkable NIR-II fluorescence imaging to guide chemo-thermal therapy.
研究领域:
生物医学工程
·
肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2017
·Vol. 41
·期 15
·7292-7301
·
IF 3.269
Yuhua Chen,Ruihan Tong,Na An,Huiming Lin,Fengyu Qu
Currently, incorporating multiple therapeutic functions into one nanostructure has attracted more and more attention for the development of efficient anticancer agents. In this study, a uniform core–shell UCNPs@mSiO2 nanocomposite was prepared as the carrier to develop the NIR light-controlled chemotherapy associated with photodynamic therapy (PDT). In view of the novel UV emission, the semiconductor photosensitizer TiO2 was exploited due to its high efficiency and chemical stability. The host modification method was used to integrate TiO2 doping and mesoporous structure, which can store anticancer drug molecules (doxorubicin, DOX). To improve the utilization of emission, a photolabile o-nitrobenzyl derivative was incorporated to form a sensitive linker (NB linker) as a “gate” to make sure the few leak. Upon NIR irradiation, the UV emission can not only excite TiO2 to produce reactive oxygen species (ROS), but also induce the breaking of NB linker as well as drug release. The NIR-triggered performances were further demonstrated by the cell experiment using HeLa cells as the model cancer cell. The synergistic effect of chemotherapy and PDT induces enhanced cytotoxicity, which is more powerful than their simple effects added together. Therefore, the novel NIR light-controlled double-therapeutic nanocomposite should be a potential candidate for anticancer agents.
研究领域:
生物医学工程
·
肿瘤治疗学
·
纳米医学
✓ 已验证
DOI
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2023
·
IF 3.6
Jie Yang,Xiao-Jie Wang,Si-Mei Li,Dong-Xue Jiang,Yu-Xin Liu,Yan Huang,Di-Di Dong,Wei Hu,Bo Liu
Nowadays, chemotherapy is a common clinical treatment for cancer, but it still faces many limitations and challenges. Therefore, the combination of chemotherapy and other treatments often enhances the effectiveness of treatments. Herein, an injectable hydrogel of PC10ARGD/Cu2+/DOX based on Cu2+, hydrophilic doxorubicin (DOX), and genetically engineered polypeptide PC10ARGD was prepared. First, Cu2+ was attached to the histidines in the PC10ARGD polypeptide by the coordination reaction to form PC10ARGD/Cu2+ hydrogel, then the PC10ARGD/Cu2+/DOX hydrogel was prepared by encapsulating the DOX into the PC10ARGD/Cu2+ hydrogel. The results of scanning electron microscopy showed that the PC10ARGD/Cu2+/DOX hydrogel displayed loose porous morphology. In vitro, reactive oxygen species production results showed that the PC10ARGD/Cu2+/DOX hydrogel could continuously produce ·OH in the presence of H2O2. In vitro MTT results showed that the PC10ARGD/Cu2+/DOX hydrogel had a good inhibitory effect on cell activity. Flow cytometry further confirmed the antitumor effect of the PC10ARGD/Cu2+/DOX hydrogel. In vivo experiment results showed that the tumor volume of mice treated with the PC10ARGD/Cu2+/DOX hydrogel was significantly inhibited compared with control groups, which was due to the combination of chemodynamic and chemotherapy. The results of body weight and blood analysis of mice showed that the PC10ARGD/Cu2+/DOX hydrogel possessed good biocompatibility.
研究领域:
生物材料
·
肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2011
·
IF 4.304
Lihong Zhang,Saijie Zhu,Lili Qian,Yuanying Pei,Yongming Qiu,Yanyan Jiang
This work was based on our recent studies that a promising conjugate, RGD-modified PEGylated polyamidoamine (PAMAM) dendrimer with doxorubicin (DOX) conjugated by acid-sensitive cis -aconityl linkage (RGD-PPCD), could increase tumor targeting by binding with the integrin receptors overexpressed on tumor cells and control release of free DOX in weakly acidic lysosomes. To explore the application of RGD-PPCD to glioma therapy, the effects of the conjugate were further evaluated in glioma model. For comparative studies, DOX was also conjugated to PEG–PAMAM by acid-insensitive succinic linkage to produce the PPSD conjugates, which was further modified by RGD to form RGD-PPSD. In vitro cytotoxicity of the acid-sensitive conjugates against C6 cells was higher than that of the acid-insensitive ones, and further the modification of RGD enhanced the cytotoxicity of the DOX-polymer conjugates as a result of the increased cellular uptake of the RGD-modified conjugates by C6 cells. In vivo pharmacokinetics, biodistribution and antitumor activity were investigated in an orthotopic murine model of C6 glioma by i.v. administration of DOX-polymer conjugates. In comparison with DOX solution, all the conjugates showed significantly prolonged half-life and increased AUC and exhibited higher accumulation in brain tumor than normal brain tissue. Although RGD-PPCD was more than 2-fold lower tumor accumulation than RGD-PPSD, it exhibited the longest survival times among all treatment groups, and therefore, RGD-PPCD conjugate provide a desirable candidate for targeted therapy of glioma.
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 Nanomedicine
·
2025
·
IF 6.5
Wentao Xu,Jiajia Zheng,Jiaqi Zhang,Houhui Shi,Weili Peng,Yang Liu,Guodong Feng,Yuguang Wang,Yi-Jun Liang,Jun Chen
Background Liver cancer is one of the most prevalent cancers globally, with approximately 90% of primary liver cancers being hepatocellular carcinomas (HCC). However, current systemic treatment options (whether monotherapy or combination therapy) are limited and offer only modest survival benefits. The effectiveness of a drug is largely determined by its concentration at the target site. Therefore, an effective drug delivery system must enhance drug accumulation at the target site, enable selective drug release there, and facilitate escape from lysosomes.Methods cRGD-Lipo@Ce6/DOX was prepared by modifying c(RGDyK) onto the surface of drug-loaded liposomes containing Chlorin e6 (Ce6) and doxorubicin (DOX) through an amide reaction. The targeting capability and uptake mechanism of cRGD-Lipo@Ce6/DOX for HCC were analyzed using flow cytometry. To investigate drug release mechanisms and changes in subcellular distribution following ultrasound stimulation, further studies were conducted. The therapeutic efficacy and biosafety of this dual-modality therapy were then evaluated in an HCC subcutaneous tumor-bearing mouse model.Results The prepared nanocomplex exhibits a surface charge of −9.91 ± 2.94 mV and an apparent size of 118.07 ± 1.46 nm. Modification of the RGD cyclic peptide on the surface of the drug-carrying liposomes enhanced the targeting and penetration efficiency for HCC. In vitro experiments on drug uptake mechanisms and release demonstrated that reactive oxygen species (ROS) generated by sonodynamic therapy (SDT) promote effective drug release from the carrier into the non-lysosomal region. The combined SDT and chemotherapy treatment achieved a 94% tumor inhibition rate and showed excellent biosafety in HCC subcutaneous tumor-bearing mice.Conclusion Therefore, the effectiveness of the combination treatment strategy utilizing SDT in conjunction with chemotherapy provides additional treatment options for patients with HCC.
研究领域:
肿瘤学
·
药剂学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2017
·
IF 3.887
Yuhua Chen,Huiming Lin,Ruihan Tong,Na An,Fengyu Qu
Recently, incorporating multiple components into one nanoplatform for anticancer theranostics has attracted most attention. Herein, a rattle-structured nanocomposite by using UCNPs (NaYF 4 :Yb,Tm@NaYF 4 ) as core coated with hollow mesoporous TiO 2 (UCNPs@mHTiO 2 ) was constructed as the nanocarrier. First, UCNPs@SiO 2 @TiO 2 was prepared, by a selective etching method to remove SiO 2 shell, to make sure the hollow mesoporous structure and high surface area (347 m 2 g −1 ) of UCNPs@mHTiO 2 . Under near-infrared (NIR) light irradiation, the UV emission can excite TiO 2 to produce ROS and to realize photodynamic therapy (PDT). In addition, the hollow structure offers space to store antitumor drug molecules (doxorubicin, DOX) and this nanocomposite also exhibits the improved DOX release in mildly acidic environment, which could greatly promote chemotherapy efficiency. Moreover, the luminescence resonance energy transfer (LRET) from UCNPs to DOX, owing to the effective distance restricted by the cavity, can be used to monitor the intercellular drug release kinetics. HeLa cells were used as the model cancer cells and the detailed cell experiments show the enhanced cytotoxicity, ascribing to the synergistic effect of chemotherapy and PDT. Therefore, the novel multifunctional nanocomposite, combining with chemotherapy, PDT, and imaging, should be a potential candidate in anticancer field.
研究领域:
生物医学工程
·
肿瘤学
·
纳米医学
✓ 已验证
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2020
·
IF 5.88
Guoping Li,Mingliang Pei,Peng Liu
Carbon quantum dots (CQDs) show promising potential for tumor imaging owing to their unique superior fluorescent properties. However, the small particle size limits their practical application. Here, pH/reduction dual-responsive comet-shaped PEGylated CQD-DOX conjugate prodrug, DOX-Hy-CQD-SS-PEG with DOX content of 28.5%, was designed with the hydrophobic acid-labile DOX conjugated CQDs as comet nucleus and the few hydrophilic bioreducible detachable PEG brushes as comet tails. The comet-shaped DOX-Hy-CQD-SS-PEG prodrug could self-assemble into unique micelles with mean diameter of 127 nm. The DOX-Hy-CQD-SS-PEG micelles possessed excellent pH/reduction dual-responsive drug release with low drug leakage of 9% in 150 h. Furthermore, the fluorescent CQDs was recovered after DOX release and de-PEGylation, demonstrating their potential application for real-time response of therapy.
研究领域:
纳米医学
·
药物递送系统
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Lu Liu,Daiyong Chao,Qing Dong,Xianli Zhang,Kai Zhang,Zhenyu Ju
Doxorubicin (DOX), a potent anthracycline chemotherapeutic agent, is widely used in cancer treatment but is associated with significant adverse effects, particularly DOX-induced cardiomyopathy (DIC). DIC pathogenesis involves the generation of reactive oxygen species (ROS) and ferroptosis induction. Novel therapeutic strategies targeting antioxidant defenses and ferroptosis inhibition are essential for mitigating DIC. An innovative bimetallic metal-organic framework (MOF), NiCu-MOF (NCM), is developed, exhibiting multifaceted antioxidant enzyme-mimicking activities that effectively scavenge a broad spectrum of ROS. Additionally, the bimetallic NCM exhibits excellent iron-chelating ability. In vitro experiments demonstrate that NCM significantly reduces cardiomyocyte death by attenuating ROS levels and inhibiting ferroptosis. Furthermore, in a mouse model of DIC, NCM treatment results in substantial myocardial protection, evidenced by improved cardiac function and structural integrity. This protective effect is attributed to suppression of ferroptosis, preservation of mitochondrial function, and attenuation of inflammatory responses. Collectively, these findings highlight biocompatible NCM's potential as a novel cardioprotective agent and offer a promising therapeutic strategy for managing DIC.
研究领域:
药理学
·
心血管病学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 113
·112232-112240
·
IF 3.289
Xiangjie Luo,Ying Wang,Huiming Lin,Fengyu Qu
The integration of multiple therapies into one nanoplatform was considered to be the most efficient method to give an enhanced therapeutic effect for anti-cancer treatments. In this research, pH sensitive drug release and near-infrared (NIR)-induced photothermal therapy (PTT) were placed in one nanocomposite using iron(II,III) oxide@meso-silica (Fe3O4@mSiO2) NPs as the host. Then, a sensitive ketal modified silane coupling agent (PO linker) was prepared to encapsulate the anti-cancer drug, doxorubicin hydrochloride (DOX), into the mSiO2 shell, ensuring the few leakage. Based on the different pH conditions of normal and cancer cells, the DOX-Fe3O4@mSiO2-PO nanocomposite exhibits the specific drug release in cancer cells (acid conditions) before that the few leakage makes sure there are a low number of side effects. Furthermore, the release kinetics can also be easily adjusted by varying the amount of PO linker. Under NIR (808 nm) irradiation, the photothermal effect derived from magnetic Fe3O4 NPs can also induce the apoptosis of the cancer cells which is how PTT is achieved. HeLa cells (cervical cancer cell line) were used as the typical cancer cell and the detailed cell experiments further display the enhanced specific cytotoxicity of the method to HeLa cells. The multifunctional nanocomposite has great potential as an application for anti-cancer therapy.
研究领域:
生物医学工程
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2015
·Vol. 3
·期 27
·5478-5489
·
IF 4.726
Yong Sun,Yaning Wang,Yani Cui,Wen Zou,Yanfei Tan,Jie Liang,Yujiang Fan,Xingdong Zhang
Stimuli-responsive targeted polymeric micelles as drug delivery systems have recently attracted significant attention for the treatment of various cancers, which could improve delivery efficiency by tumor-specific recognition via active targeting strategies. In this research, DOX-incorporated bioreducible polymeric micelles based on PAA-g-PEG/PEG–Fa conjugated polymers were prepared and characterized as nanocarriers for promoting intracellular anti-tumor drug delivery efficiency via folate receptor-mediated endocytosis. The anti-proliferative activity on cancer cells, biodistribution, active-/passive-targeting efficiency, tumor growth inhibition efficiency, and biological toxicity were evaluated in vitro and in vivo. The MTT assay demonstrated that the DOX-encapsulated active-targeting PAA-g-PEG/PEG–Fa micelles had much greater growth inhibition effect against 4T1 and KB than passive-targeting micelles. These active-targeting micelles showed superior tumor accumulation and excellent tumor growth inhibition effect as revealed by the fluorescence optical imaging technique and tumor volume change investigation, as well as the survival study of the tumor-bearing Balb/c mice. Furthermore, the active targeting micelles greatly decreased the toxicity of DOX on the heart and other organs. These potential results encouraged us to further optimize the molecular structure to achieve more excellent targeted therapeutic effect.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）