Artificial Cells Nanomedicine and Biotechnology
·
2019
·
IF 4.462
Chenghua Liang,Nan Li,Zikai Cai,Rongpu Liang,Xiaoming Zheng,Li Deng,Longbao Feng,Rui Guo,Bo Wei
At present, cancer is the first cause of death for humans, but early detection and treatment can help improve prognoses and reduce mortality. However, further development of carrier-assistant drug delivery systems (DDSs) is retarded by the aspects such as the low drug-carrying capacity, carrier-induced toxicity and immunogenicity, complex synthesis manipulation. The development of nanoscale drug delivery systems (NDDS) have been rapidly developed to address these issues. In this article, we used PLGA-PEG with good biocompatibility to encapsulate Fe3O4 nanoparticles (a magnetic resonance imaging contrast agent) and DOX (an antitumour drug) via the emulsion-solvent evaporation method, aimed at achieving a dual function of the early detection and the treatment of mammary cancer. The results showed that the Fe3O4/DOX/PLGA-PEG nanoparticles had a relatively uniform size, a high carrier rate of Fe3O4 and high encapsulation efficiency of DOX, and a relatively high activity of released DOX within 120 h. In addition, in vitro studies showed that the Fe3O4/DOX/PLGA-PEG nanoparticles were cytocompatibility in NIH 3T3 fibroblast cells culture study while had a special effect on destroying human breast cancer MCF-7 cells compared with pure DOX solution. In vitro studies revealed that the Fe3O4/DOX/PLGA-PEG enabled enhanced T2 contrast magnetic resonance. Overall, our multifunctional Fe3O4/DOX/PLGA-PEG nanoparticles, composed of biocompatible substances and therapeutic/imaging materials, have great potential for the early detection of cancer and accurate drug delivery via the dynamic monitoring using MRI.
研究领域:
生物医学工程
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纳米医学
·
肿瘤学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2025
·Vol. 15
·期 3
·1507-1513
·
IF 4.6
Wei Li,Yan Wang,Hongkun Miao,Maohui Yan,Chen Liu,Yu Wang,Jianjun Zhang,Zhiguang Fu
Oral squamous cell carcinoma is one of the most common types of cancer. Surgical resection is one of the most important treatments at present. However, patients often suffer from regional recurrence after surgery. Therefore, new strategies for combination therapy need to be investigated. This work identified a smart injectable hydrogel system co-delivering DOX and sunitinib nanoparticles. The nano drugs are continuously released from the hydrogels and effectively taken up by cells. The nano drugs in the hydrogel can inhibit tumor cell viability and induce cancer cell apoptosis in vitro. The drug-loaded hydrogel could control the recurrence of subcutaneous xenograft tumors, prolong the survival time, and have no obvious toxicity in nude mice. These findings suggest that this smart injectable hydrogel system may provide new ideas for the comprehensive treatment of oral squamous cell carcinoma.
研究领域:
肿瘤学
·
药剂学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LANGMUIR
·
2023
·
IF 3.9
Hailiang Chen,Chenyu Liu,Simiao Yu,Hengjun Zhou,Farishta Shafiq,Weihong Qiao
The resistance of cancer cells to anticancer drugs has been recognized as one of the main reasons for chemotherapy failure. Multidrug combination therapy is one of the most effective ways to solve this problem. Therefore, in this article, we designed and synthesized a pH/GSH dual-responsive camptothecin/doxorubicin (CPT/DOX) dual pro-drug synergistic treatment system with the aim of overcoming the resistance of non-small cell lung cancer A549/ADR cells to DOX. The pro-drug cRGD-PEOz-S-S-CPT (cPzT) was obtained by linking CPT to poly(2-ethyl-2-oxazoline) (PEOz) with endosomal escape properties through a GSH-responsive disulfide bond and modifying it with the targeted peptide cRGD. The pro-drug mPEG–NH–N=C-DOX (mPX) was synthesized by attaching DOX to polyethylene glycol (PEG) through acid-sensitive hydrazone bonds. The dual pro-drug micelles cPzT/mPX configured according to the CPT/DOX mass ratio of 3:1 showed a strong synergistic therapeutic effect at IC50 with a combined therapy index CI = 0.49, far less than 1. Moreover, with the further improvement of the inhibition rate, the 3:1 ratio showed a stronger synergistic therapeutic effect than other ratios. The cPzT/mPX micelles not only had better targeted uptake ability but also showed a better therapeutic effect in both 2D and 3D tumor suppression assays relative to free CPT/DOX and significantly enhanced the penetration ability into solid tumors. In addition, the results of confocal laser scanning microscopy (CLSM) showed that cPzT/mPX could effectively overcome the resistance of A549/ADR cells to DOX by delivering DOX into the nucleus to exert its effect. Thus, this dual pro-drug synergistic therapy system combining targeting and endosomal escape ability provides a possible strategy to overcome tumor drug resistance.
研究领域:
药学
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肿瘤学
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2020
·
IF 0
Weijun Fang,Wenjuan Zhu,Hu Chen,Hanyuan Zhang,Shi Hong,Wenmei Wei,Tingting Zhao
Developing of multifunctional nanoplateforms for simultaneous accurate cancer detection and target therapy is essential in cancer treatment. Herein, we present a facile synthesis of DOX/MNPs-FA nanocomposites for high-performance MRI and tumor-targeted drug delivery. In such core–shell structured DOX/MNPs-FA nanocomposite, the high magnetism of iron oxide core can be tuned and achieved by controlling the Zn2+ dopant amount, making them suitable as excellent contrasts in T2-weighted MR imaging. The outer porous silica shell with large pores about 5.4 nm in diameter possesses high surface area and pore volume. Anticancer drug (DOX molecules) can be stored in the large pore channels and is triggered to be released under acidic condition (pH 4–6). Importantly, the presence of folic acid on the surface of DOX/MNPs-FA allows the targeted delivery of the DOX to tumor cells, and therefore improves tumor chemotherapy efficiency. Our in vitro studies also demonstrated that DOX/MNPs-FA could be efficiently internalized into HeLa cells via the folate receptor-mediated endocytosis, and generate a greater cytotoxicity toward cancer cells compared to free DOX and DOX/MNPs. Therefore, these DOX/MNPs-FA multifunctional nanocomposites have great potential applications for simultaneous tumor diagnosis and targeted chemotherapy.
研究领域:
生物医学工程
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癌症治疗
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材料科学
✓ 已验证
产品关联
DOI
PubMed
RSC Advances
·
2017
·Vol. 7
·期 63
·39641-39650
·
IF 3.108
Yanhong Duo,Yang Li,Changke Chen,Baiyun Liu,Xinyu Wang,Xiaowei Zeng,Hongbo Chen
The development of multifunctional nano drug delivery carriers has been one of the most effective and prevailing approaches to overcome drug non-selectivity, low cell uptake efficiency and various side effects of traditional chemotherapy drugs. Herein, we report a novel doxorubicin (DOX)-loaded mesoporous silica nanoparticle (MSN) coated with polydopamine (PDA) and polyethylene glycol (PEG) (MSNs-DOX@PDA-PEG) for the treatment of breast cancer. In this system, PDA functions as a pH-sensitive gatekeeper to control the release of DOX from MSNs in response to pH-stimulus and PEG was further grafted on the surface of PDA to increase the stability and biocompatibility under physiological conditions. The in vitro release results suggested that MSNs-DOX@PDA-PEG exhibits a high sensitivity to low pH. A cellular uptake assay showed a high cellular uptake efficiency of MSNs-DOX@PDA-PEG compared to free DOX. Furthermore, MSNs-DOX@PDA-PEG also demonstrated an improved anti-cancer efficacy compared to free DOX both in vivo and vitro breast cancer experiments. Mechanistic studies revealed that MSNs-DOX@PDA-PEG causes a stronger pro-death autophagy compared to free DOX via inhibition of the AKT-mTOR-p70S6K signaling pathway. Taken in concert, our results suggest that the novel material MSNs-DOX@PDA-PEG may represent a promising nanoformulation for breast cancer treatment.
研究领域:
纳米技术
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药学
·
肿瘤学
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生物医学工程
✓ 已验证
DOI
高影响因子
DRUG DELIVERY
·
2025
·
IF 8.1
Jinguo Li,Yuhao Zhang,Changyu Shao,Yining Bai,Puxiu Wang,Tianyang Ren
Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer and is characterized by high invasiveness, rapid recurrence, and poor prognosis. To date, the ferroptosis-combined therapies have exerted their potential in the TNBC treatments via multi-mechanisms. Here, we reported a doxorubicin (DOX)–Fe complex and RSL3 co-loaded liposomes (DOX–Fe/RSL3@LIPs) for ferroptosis-enhanced chemotherapy on TNBC tumors. This nanoformulation performed a uniform spherical structure with a mean particle size of 126.9 nm, a zeta potential of −3.56 mV, and high colloidal stability. The pH-responsive dissociation of DOX–Fe and release of DOX were conducive to drug accumulation in the tumor microenvironment and tumor cells, meanwhile efficiently suppressed free DOX leakage in the blood circulation, potentially reducing the cardiotoxicity of DOX. In vitro cell and in vivo pharmacodynamic studies demonstrated a favorable anticancer effect of the DOX–Fe/RSL3@LIPs on 4T1 tumors by synchronously delivering biologically active DOX, Fe2+, and RSL3 to the tumor sites. DOX induced tumor cell death through a dual pathway of apoptosis/ferroptosis, and promoted the H2O2 generation. The tumor cell ferroptosis was observably enhanced via supplements of the ferrous ions and H2O2, and RSL3-derived GPX4 inhibition to severely destroy the oxidation balance in cells. In this paper, the DOX–Fe/RSL3@LIPs have exerted a synergistic anticancer effect on TNBC by combining ferroptosis and conventional chemotherapy, and made a meaningful exploration of new strategies for TNBC therapy.
研究领域:
肿瘤学
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纳米医学
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癌症治疗
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细胞死亡机制
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药物递送系统
✓ 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
Yaning Li,Yue Wang,Hongchao Ma
The tumor microenvironment (TME), characterized by hypoxia, limited H 2 O 2 availability, and elevated glutathione (GSH) concentrations, challenges reactive oxygen species (ROS)-based therapies. To address these, we developed a GOx@Cu-ZIF-8/DOX (GCZD) nanoplatform combining chemotherapy (CT), chemodynamic therapy (CDT), and starvation therapy (ST). This system utilizes Cu-incorporated ZIF-8 (Cu-ZIF-8) as a versatile carrier to load glucose oxidase (GOx) and doxorubicin (DOX). Under acidic TME conditions, GCZD disintegrates, releasing GOx, Cu 2+ , and DOX. GOx catalyzes intratumoral glucose oxidation, producing gluconic acid and H 2 O 2 to achieve a triple-therapeutic effect. Gluconic acid maintains a weakly acidic environment for continuous GCZD degradation. Glucose depletion induces metabolic starvation. Generated H₂O₂ serves as substrate for Cu 2+ -mediated Fenton-like reactions, boosting ROS production. Cu 2+ exhibits catalytic activity, efficiently converting TME and GOx-generated H 2 O 2 into cytotoxic ·OH. Increased ROS concentration enhances biological macromolecule oxidation damage, intensifying CDT. Additionally, Cu 2+ oxidizes GSH to form GSSH and Cu + . This inhibits GSH-mediated ROS degradation and leverages excellent Fenton-like activity of Cu + to further enhance CDT. Simultaneously, DOX exerts chemotherapeutic effects by intercalating into DNA and inhibiting topoisomerase II, blocking tumor cell proliferation. This integrated approach, combining enhanced ROS generation, tumor cell metabolic intervention, and DNA damage, demonstrates enhanced antitumor efficacy by simultaneously targeting multiple cancer cell vulnerabilities.
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Nanomedicine
·
2025
·
IF 6.5
Size Wu,Chengfang Wang
Purpose: To investigate whether multi-focused acoustic radiation force impulse (MF-ARFI) applied to murine xenograft liver tumors prior to intravenous administration of doxorubicin-loaded PEGylated liposomes (DOX@Lip) can enhance drug delivery efficiency through modulating the enhanced permeation and retention effect of the tumor, reduce side effects, and improve antitumor effect.Materials and Methods: DOX@Lip and tumor-mimetic matrices were synthesized and characterized. Huh-7 cells and DOX@Lip were exposed to MF-ARFI and observed. MF-ARFI was applied to both tumor-mimetic matrices and saline with DOX@Lip to assess displacement effects. Subsequently, murine xenograft models were established and underwent MF-ARFI preconditioning before DOX@Lip injection. Tumor volume dynamics and body weight changes were longitudinally monitored. Terminal assessments included histopathology (H&E), apoptosis (TUNEL), and molecular profiling (BCL-2 and BAX by Western blot) of tumors and major organs.Results: There was no significant difference in the live/dead cell staining results between the Huh7 cells with and without MF-ARFI. There was no significant difference in cell apoptosis rates of Huh7 cells between DOX@Lip and DOX@Lip+MF-ARFI. MF-ARFI exposure induced measurable displacement of DOX@Lip in both tumor-mimetic matrices and saline. Mice receiving combined DOX@Lip and MF-ARFI treatment exhibited significantly attenuated tumor growth (p< 0.05) and slight weight loss, which were significantly different from DOX and DOX+MF-ARFI treatments. Cardiac histopathology revealed no significant differences in myocardial toxicity between DOX@Lip and DOX@Lip+MF-ARFI groups relative to PBS controls. Conversely, tumors from the DOX@Lip+MF-ARFI group demonstrated distinct histopathological alterations compared to other groups. TUNEL staining results indicated a relatively higher level of cell apoptosis in mice treated with DOX@Lip+MF-ARFI. Molecular analyses showed MF-ARFI pretreatment significantly reduced BCL-2 expression (p< 0.05) while elevating the BAX/BCL-2 ratio versus DOX@Lip monotherapy.Conclusion: Preconditioning xenograft tumors with MF-ARFI prior to DOX@Lip administration faciliates DOX@Lip delivery and significantly enhances antitumor effect while reducing cardiotoxicity. This combinatorial strategy demonstrates translational potential for optimizing liposomal chemotherapeutic delivery and effect.Plain Language Summary: Doxorubicin (DOX) can be used for the therapy of some liver cancers ineligible for surgery. However, DOX has severe side effects in high concentration. Using liposomes to encapsulate DOX to form nanoscale DOX@Lip can control the release of DOX in the blood circulation and reduce side effects. DOX@Lip can pass the tumor capillary and accumulate in the tumor stroma and release sustainably. However, its release efficiency can be impacted by the tumor stroma status. If the tumor stroma becomes stasis due to necrotic tumor and other cellular debris after previous treatments, the subsequently administrated drug will be difficult to pass the capillaries to accumulate in the tumor stroma. Multi-focused acoustic radiation force impulse (MF-ARFI) is a kind of low-intensity ultrasound, with it irradiation of liver tumor, the structures of tumor stroma can occur push, pull, and displacement, facilitating the drug leak out the capillaries, promoting the waste substances in the stroma moving away. Therefore, using MF-ARFI before nanoscale drug administration can facilitate the drug delivery and distribution in the tumor. The results of this study showed that using MF-ARFI irradiated xenograft liver tumor of mice followed by intravenous infusion of DOX@Lip significantly enhanced anti-cancer effect and reduce side effects.
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产品关联
DOI
PubMed
高影响因子
International Journal of Polymeric Materials and Polymeric Biomaterials
·
2017
·
IF 1.515
Yan-Ling Luo,Xue-Yin Zhang,Jing-Yu Fu,Feng Xu,Ya-Shao Chen
Novel poly(N-isopropylacrylamide)/carboxymethyl chitosan/multiwalled carbon nanotube semi-interpenetrating nanohybrid hydrogels were prepared, and the chemical structure and morphology were characterized. The prepared hydrogels showed temperature and pH dual-responsiveness, and the one containing multiwalled carbon nanotubes (MWCNTs)–COOH possessed high maximal swelling ratios. The phase transition produced at pH of 6.8–7.4 and temperature of 35–40°C, hinging on the system compositions and charge ratios. The hydrogels were used to load hydrophilic anticancer drug, with high entrapped efficiency of about 44%. The drug release changed with temperature, pH, and MWCNTs–COOH contents. The designed hydrogels can be used for site-specific target delivery of protein or hydrophilic anticancer drug.
研究领域:
材料科学
·
生物医药工程
·
药剂学
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Nanomedicine
·
2017
·
IF 4.3
Shengnan Huang,Chunming Li,Weiping Wang,Huanjie Li,Zhi Sun,Chengzhi Song,Benyi Li,Shaofeng Duan,Yurong Hu
The combination of photothermal therapy and chemotherapy (photothermal–chemotherapy) is a promising strategy for cancer therapy. Gold nanocages (AuNCs), with hollow and porous structures and unique optical properties, have become a rising star in the field of drug delivery. Here, we designed a novel targeted drug delivery system based on functionalized AuNCs and evaluated their therapeutic effects in vitro and in vivo. We then loaded doxorubicin into this promising system, designated as DHTPAuNCs consisting of hyaluronic acid-grafted and A54 peptide-targeted PEGylated AuNCs. Its formation was corroborated by ultraviolet–visible spectroscopy, transmission electron microscopy and dynamic light scattering. This delivery platform needed hyaluronidase to release encapsulated drugs, meanwhile the acidic pH and near-infrared irradiation could accelerate the release. In addition, the results of cellular uptake demonstrate that this system could bind specifically with BEL-7402 cells. In vitro, we evaluated therapeutic effects of the DHTPAuNCs in BEL-7402 cells by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide assay. Moreover, in BEL-7402 tumor-bearing nude mice, its therapy effect in vivo was also evaluated. As expected, DHTPAuNCs exhibited excellent therapeutic effect by photothermal–chemotherapy, both in vitro and in vivo. In short, DHTPAuNCs with low toxicity showed great potential as a drug delivery system for cancer therapy.
研究领域:
纳米技术
·
癌症治疗
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2015
·Vol. 3
·期 46
·8949-8962
·
IF 4.726
Lidi Chen,Yanan Xue,Xiaoyang Xia,Meifang Song,Juan Huang,Han Zhang,Bo Yu,Sihui Long,Yanping Liu,Lei Liu,Shiwen Huang,Faquan Yu
A reduction-triggered superparamagnetic nanogel was designed for enhancing targeting release but minimizing leakage of drug in the drug-transportation pathway. Doxorubicin (DOX) was first conjugated onto sodium alginate (SA) with a disulfide linker (SA-SS-DOX). SA-SS-DOX was then electrostatically assembled with aminated superparamagnetic iron oxide nanoparticles for the preparation of nanogel. The nanogel was estimated with a size of 122 ± 15 nm, a polydispersity index of 0.178, a surface charge of around −36.0 mV, a DOX loading of 7.2 wt%, and a saturation magnetization of 40.0 emu g−1 Fe. In vitro release profiles showed a significantly high accumulative release at pH 5.5/10 mM Glutathione (GSH) but pretty low release at pH 7.4/pH 5.5 without GSH, exhibiting apparent reduction responsiveness. In vitro cytotoxicity tests clearly illustrated that the effective selectivity of killing the human cervical cancer cells (HeLa) with a IC50 of 0.30 μg mL−1, significantly enhanced the cytotoxicity of the African green monkey Sv40-transformed kidney fibroblast cells (COS-7). Prussian blue staining and quantification of cellular iron and protein concentration revealed apparent iron uptake by HeLa cells. Confocal laser scanning microscopy observation demonstrated that DOX was efficiently internalized into HeLa cells, released into the cytoplasm, and then principally entered the nuclei. In vivo investigation exhibited that nanogel treatment induced obvious shrinkage in tumor volume but a stable growth in body weight and a healthy appearance. Hematoxylin-eosin (H&E) staining indicated remarkable necrosis in the tumor area and histologic examination revealed lower toxicity in vital organs. Thus this kind of nanogel expressed high targeted release but low systemic toxicity. It is thus believed that this nanogel will offer a promising candidate for highly effective cancer therapy.
研究领域:
药剂学
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肿瘤学
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生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2017
·
IF 3.887
Jilian Wu,Huiyuan Zhang,Xu Hu,Ruiling Liu,Wei Jiang,Zhonghao Li,Yuxia Luan
Clinically, codelivery of chemotherapeutics has been limited by poor water-solubility and severe systemic toxicity. In this work, we developed a new reduction-sensitive mixed micellar system for self-codelivery of doxorubicin (DOX) and docetaxel (DTX). Biodegradable methoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) was coupled with DOX and DTX by a reduction-sensitive disulfide bond, resulting in mPEG-PCL-SS-DOX and mPEG-PCL-SS-DTX, respectively. mPEG-PCL-SS-DOX was mixed with mPEG-PCL-SS-DTX at a mole ratio of 1:1 in water, forming a mixed micellar system. The mixed micelles had a diameter of 223.7 nm and a low critical micelle concentration. Reductive-triggered drug release revealed a “smart” characteristic of the mixed micelles. A cellular uptake and cytotoxicity assay in vitro showed that the mixed micelles could efficiently accumulate in MCF-7 cells and suppress the growth of tumour cells. The proposed reduction-sensitive mixed micelles assembled from amphiphilic prodrugs can be used as a promising drug codelivery system for cancer therapy.
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）