JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
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2022
·
IF 3.682
Yongli Shi,Chunyan Li,Mingbo Yang,Xiaofei Pan,Jie Hu
In this study, novel redox-sensitive nanoparticles (NPs) were fabricated from the poly(caprolactone) conjugates with disulfide-linked poly(ethylene glycol) (DDMAT- mPEG-S-S-PCL, DPSP). The DPSP polymer was synthesized by ring-opening polymerization (ROP) and reversible addition-fragmentation chain transfer (RAFT) polymerization. The obtaining of the DPSP polymer was confirmed by the 1H nuclear magnetic resonance (1H NMR) and Fourier transform infrared spectroscopy (FTIR) spectra. The DPSP NPs were fabricated with the solvent-evaporation method. Docetaxel (DTX) was employed as a model drug and encapsulated into the DPSP NPs. The in vitro anti-tumor activity of the DTX-loaded DPSP NPs and free DTX against the breast cancer cells (4T1) were evaluated by MTT assay. The cargo-free DPSP NPs were in circular shapes with an average diameter of 107.8 ± 0.4 nm. These NPs displayed redox-responsive behavior in the presence of glutathione. Animal experiments indicated that the DPSP NPs showed excellent blood compatibility and good bio-security. Cell tests suggested that the DPSP NPs could be taken in by 4T1 cells, smoothly, which improved the anti-tumor activity of free DTX.
研究领域:
药剂学
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肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2016
·
IF 4.32
Ping Sun,Wei Huang,Mingji Jin,Qiming Wang,Bo Fan,Lin Kang,Zhonggao Gao
Nanoparticle-mediated small interfering RNA (siRNA) delivery is a promising therapeutic strategy in various cancers. However, it is difficult to deliver degradative siRNA to tumor tissue, and thus a safe and efficient vector for siRNA delivery is essential for cancer therapy. In this study, poly(ethylene glycol)-modified chitosan (PEG-CS) was synthesized successfully for delivering nucleic acid drug. We deemed that PEGylated CS could improve its solubility by forming a stable siRNA loaded in nanoparticles, and enhancing transfection efficiency of siRNA-loaded CS nanoparticles in cancer cell line. The research results showed that siRNA loaded in PEGylated CS (PEG-CS/siRNA) nanoparticles with smaller particle size had superior structural stability in the physical environment compared to CS nanoparticles. The data of in vitro antitumor activity revealed that 4T1 tumor cell growth was significantly inhibited and cellular uptake of PEG-CS/siRNA nanoparticles in 4T1 cells was dramatically enhanced compared to naked siRNA groups. The results from flow cytometry and confocal laser scanning microscopy showed that PEG-CS/siRNA nanoparticles were more easily taken up than naked siRNA. Importantly, PEG-CS/siRNA nanoparticles significantly reduced the growth of xenograft tumors of 4T1 cells in vivo. It has been demonstrated that the PEG-CS is a safe and efficient vector for siRNA delivery, and it can effectively reduce tumor growth and prevent metastasis.
研究领域:
癌症治疗
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药学
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纳米技术
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
STAR Protocols
·
2023
·
IF 0
Yunfei Yi,Chan Feng,Mian Yu,Lin Mei,Meiying Wu,Wei Tao
Summary Efficient gene delivery in an integrated drug delivery system is urgent for multimodal antitumor therapy. Herein, we describe a protocol for constructing a peptide-based siRNA delivery system to achieve tumor vascular normalization and gene silencing in 4T1 cells. We highlighted four major steps, including (1) synthesis of the chimeric peptide, (2) preparation and characterization of P A7R @siRNA micelleplexes, (3) in vitro tube formation assay and transwell cell migration assay, and (4) siRNA transfection in 4T1 cells. This delivery system is expected to be used to silence gene expression, normalize tumor vasculature, and perform other treatments based on the different peptide segments. For complete details on the use and execution of this protocol, please refer to Yi et al. (2022). 1
研究领域:
癌症生物学
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分子生物学
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药学
·
生物技术
✓ 已验证
DOI
PubMed
ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Yongfei Huang,Junping Liang,Wenbo Lu,Chenzhong Li,Zhefeng Fan
Cancer is a serious threat to human health, and it is essential to find effective methods for detecting and treating cancer. Diagnostic integration is a new strategy for cancer diagnosis and treatment that enables localized detection and treatment of tumors in a single administration and effectively reduces the toxic side effects on normal tissues. It remains a challenge for small-molecule probes to achieve multifunctionality in sensing, targeting, imaging, and therapy. Photodynamic therapy (PDT), which uses photosensitizers to generate reactive oxygen species under specific wavelengths of light to ablate tumor tissue, has demonstrated unique advantages in tumor treatment. However, the high expression of Cys/GSH in the tumor region will consume the reactive oxygen species generated by photosensitizers during PDT and reduce the therapeutic effect of the tumor. In this study, the highly expressed Cys/GSH in the tumor microenvironment was used as the activation source, and benzopyrylium salt and coumarin dyes were selected as fluorophores, with the ether bond and aldehyde group as recognition sites, to construct a near-infrared-activated Cys/GSH fluorescent probe (Bpl-O-Cou). Based on the intramolecular rearrangement mechanism and intramolecular cyclization mechanism, Bpl-O-Cou could discriminate the detection of Cys/GSH accompanied by different fluorescence emissions. Under near-infrared laser irradiation, Bpl-O-Cou + Cys/GSH could produce •OH and O2–•, leading to 4T1 cell death. In vivo experiments further illustrated the interventional role of Bpl-O-Cou in the PDT process. This study provides a new idea for the design of multifunctional probes for cancer diagnostics and therapeutics.
研究领域:
肿瘤学
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生物化学
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药理学
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分子成像
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诊疗一体化
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光医学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Yadong Liu,Yifan Xue,Junjie Tang,Peng Zhang,Changjiang Liu,Dalin Wu,Jie Liu
Porphyrin-based photosensitizers are extensively utilized in the realm of photodynamic therapy, capitalizing on their advantageous optical, chemical, and electronic properties. Nonetheless, their application is often constrained by their pronounced hydrophobicity. Structures with a high load capacity and excellent biocompatibility are preferred options to circumvent this obstacle. Herein, we constructed a novel porphyrin–camptothecin (CPT) polymer, which is composed of amphiphilic oxazoline segments, and the drug monomers containing disulfide bonds are modified on the hydrophobic chain of polyoxazoline. The polyoxazoline–porphyrin–CPT (OPC) polymer can self-assemble into nanoparticles in the aqueous phase, possesses excellent stability, and generates abundant singlet oxygen (1O2) under laser irradiation. Additionally, the OPC nanoparticles exhibit satisfactory biocompatibility and high light toxicity against 4T1 cells. In the microenvironment of the tumor, drugs were released from the OPC nanoparticles owing to the high concentration of GSH, causing direct damage to the tumor cell, achieving the combination of photo-chemotherapy. The findings of this research indicate that polyoxazoline porphyrin demonstrates adaptability as a nanoplatform for cancer treatment.
研究领域:
药学
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纳米技术
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生物医学工程
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Arabian Journal of Chemistry
·
2023
·
IF 6
Xue Wang,Mengli Zhao,Jianmin Feng,Dejun Li
In this paper, polycrystalline molybdenum disulfide (MoS 2 ) nanoflowers were prepared by mixing ammonium molybdate tetrahydrate [(NH 4 ) 6 Mo 7 O 24 ·4H 2 O] and potassium thiocyanate (KSCN) at 300 °C for 2 h via molten salt sintering method. Under scanning electron microscope (SEM) and high-resolution transmission electron microscope (HRTEM), MoS 2 showed popcorn-like shape, which surface distribution defects were easy to be further modified. MoS 2 as a nano-enzyme was used to inhibit the proliferation of mouse breast cancer cells (4 T1), which had 69.8 % inhibitory effect on 4 T1 cell proliferation. Electron spin resonance (ESR) analysis showed that MoS 2 could produce a large number of stable hydroxyl radicals (–OH). The disulfide bond in MoS 2 was highly sensitive to reactive oxygen species (ROS). High ROS level leads to the death of cancer cells under oxidative stress and inhibits the proliferation of 4 T1. This work demonstrates that MoS 2 is a potential anticancer drug or carrier for cancer treatment.
研究领域:
材料科学
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纳米技术
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癌症研究
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生物医学工程
✓ 已验证
DOI
高影响因子
POWDER TECHNOLOGY
·
2018
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IF 3.23
Chao Qin,Xin Yang,Yubing Wu,Yaqi Lv,Li Zhang,Xiaofei Xin,Lei Yang,Wei He,Xiaopeng Han,Lifang Yin,Chunyong Wu
ABSTRACT A matrix metalloproteinases (MMPs) triggered multifunctional micellar system loading traditional chemotherapeutic agent paclitaxel (PTX) and marimastat (MATT), an inhibition of matrix metalloproteinases, was established to prevent tumor growth and metastasis. The micelles were self-assembled by the conjugate synthesized with an MMPs sensitive peptide as the bridge between PTX and poly(ethylene glycol) (PEG). 4T1 cell line derived from a murine breast tumor was selected as the cell model due to its high metastasis. The cytotoxicity assay and cell apoptosis analysis revealed that the sensitive micelles increased the toxicity and cell apoptosis compared with the insensitive micelles. In addition, this system also exhibited high penetration ability in tumor spheroids and significant invasion inhibition with the method of Transwell invasion assay. In the BALB/c mice bearing 4T1 tumors, this system inhibited the growth of the metastatic tumor and prevented the incidence of lung metastasis with low systemic toxicity. And the expression of MMP-2 and MMP-9, which are important in the process of tumor metastasis, was down-regulated. Generally, the data obtained from the in vitro and in vivo studies confirmed that the codelivery of PTX and MATT by the MMPs sensitive micelles achieved not only significant antitumor effect but also obvious inhibition effect of tumor metastasis, which are the leading cause of cancer deaths. This functional particle system may provide a promising strategy for metastatic breast cancer therapy.
研究领域:
肿瘤学
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药学
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
Pharmaceutics
·
2024
·Vol. 16
·期 5
·632
·
IF 4.9
Weixiang Fang,Kailing Yu,Songhan Zhang,Lai Jiang,Hongyue Zheng,Qiaoling Huang,Fanzhu Li
A nanoparticle’s shape is a critical determinant of its biological interactions and therapeutic effectiveness. This study investigates the influence of shape on the performance of mesoporous silica nanoparticles (MSNs) in anticancer therapy. MSNs with spherical, rod-like, and hexagonal-plate-like shapes were synthesized, with particle sizes of around 240 nm, and their other surface properties were characterized. The drug loading capacities of the three shapes were controlled to be 47.46%, 49.41%, and 46.65%, respectively. The effects of shape on the release behaviors, cellular uptake mechanisms, and pharmacological behaviors of MSNs were systematically investigated. Through a series of in vitro studies using 4T1 cells and in vivo evaluations in 4T1 tumor-bearing mice, the release kinetics, cellular behaviors, pharmacological effects, circulation profiles, and therapeutic efficacy of MSNs were comprehensively assessed. Notably, hexagonal-plate-shaped MSNs loaded with PTX exhibited a prolonged circulation time (t1/2= 13.59 ± 0.96 h), which was approximately 1.3 times that of spherical MSNs (t1/2= 10.16 ± 0.38 h) and 1.5 times that of rod-shaped MSNs (t1/2= 8.76 ± 1.37 h). This research underscores the significance of nanoparticles’ shapes in dictating their biological interactions and therapeutic outcomes, providing valuable insights for the rational design of targeted drug delivery systems in cancer therapy.
研究领域:
纳米技术
·
癌症治疗
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2019
·Vol. 8
·期 1
·325-332
·
IF 5.251
Haiyang Yu,Na Shen,Yanli Bao,Li Chen,Zhaohui Tang
Although the polymeric vascular disrupting agent (poly(L-glutamic acid)-graft-methoxy poly(ethylene glycol)/combretastatin A4) nanoparticles (CA4-NPs) has great potential to inhibit cancer growth, it is still a challenge to avert tumor recurrence and metastasis after treatment. It is mainly tightly associated with hypoxia induced by CA4-NPs, which can activate many downstream genes regulating tumor growth and metastasis. Herein, to relieve a tumor hypoxia microenvironment, the mTOR inhibitor temsirolimus was employed to modulate the tumor microenvironment when treated with CA4-NPs. In vitro MTT experiments strongly verified that the combination of temsirolimus with polymeric CA4-NPs exhibited an additive toxicity to 4T1 cells. An in vivo study with the 4T1 mammary adenocarcinoma model revealed that consistent with the proposed scenario, combination therapy with CA4-NPs plus temsirolimus suppressed tumor growth significantly more strongly compared to either CA4-NPs or temsirolimus monotherapy, and the inhibition rate to 4T1 tumor with a volume of 300 mm3 was 71%. The mechanism underling combination treatment was confirmed by western blotting and immunofluorescence staining, and the results demonstrated that temsirolimus could inhibit HIF1α expression. Thus, this work provides a mechanistic rationale for the use of VDAs in combination with the mTOR inhibitor to enhance anticancer efficacy, delaying tumor recurrence and inhibiting tumor metastasis.
研究领域:
肿瘤学
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药理学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Ping Ji,Xin-Chen Deng,Xiao-Kang Jin,Shi-Man Zhang,Jia-Wei Wang,Jun Feng,Wei-Hai Chen,Xian-Zheng Zhang
Tumor immunotherapy is commonly hindered by inefficient delivery and presentation of tumor antigens as well as immunosuppressive tumor microenvironment. To overcome these barriers, a tumor-specific nanovaccine capable of delivering tumor antigens and adjuvants to antigen-presenting cells and modulating the immune microenvironment to elicit strong antitumor immunity is reported. This nanovaccine, named FCM@4RM, is designed by coating the nanocore (FCM) with a bioreconstituted cytomembrane (4RM). The 4RM, which is derived from fused cells of tumorous 4T1 cells and RAW264.7 macrophages, enables effective antigen presentation and stimulation of effector T cells. FCM is self-assembled from Fe(II), unmethylated cytosine-phosphate-guanine oligodeoxynucleotide (CpG), and metformin (MET). CpG, as the stimulator of toll-like receptor 9, induces the production of pro-inflammatory cytokine and the maturation of cytotoxic T lymphocytes (CTLs), thereby enhancing antitumor immunity. Meanwhile, MET functions as the programmed cell death ligand 1 inhibitor and can restore the immune responses of T cells against tumor cells. Therefore, FCM@4RM exhibits high targeting capabilities toward homologous tumors that develop from 4T1 cells. This work offers a paradigm for developing a nanovaccine that systematically regulates multiple immune-related processes to achieve optimal antitumor immunotherapy.
研究领域:
癌症免疫学
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纳米技术
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药学
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免疫治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2022
·
IF 6.51
Yanzhi Wang,Cancan Sun,Leaf Huang,Mengqian Liu,Lu Li,Xiping Wang,Linchao Wang,Shanshan Sun,Haiwei Xu,Gege Ma,Lei Zhang,Jiaxin Zheng,Hongmin Liu
The potential of combination therapy using nanoparticle delivery systems in improving triple-negative breast cancer treatment efficacy remains to be explored. Here, we report a novel nanoparticle system using a cholesterol biguanide conjugate hydrochloride (CBH) as both a drug and carrier to load magnolol (MAG). Poly(ethylene glycol)-poly(lactic-co-glycolic acid) (mPEG-PLGA) and aminoethyl anisamide-poly(ethylene glycol)-poly(lactic-co-glycolic acid) (AEAA-PEG-PLGA) were added to form nanoparticles. Nanoparticles accumulated most in tumor tissues when the weight ratio of AEAA-PEG-PLGA to mPEG-PLGA was 4:1. MAG and CBH exerted a synergistic inhibitory effect on 4 T1 cells. An in vitro study showed that nanoparticles displayed the highest tumor cell uptake rate, highest apoptosis rate, and strongest inhibitory effect on tumor cell migration and monoclonal formation. CBH might promote nanoparticle uptake by cells and lysosomal escape. After intravenous administration to mice with 4 T1 breast tumors in situ , the nanoparticles inhibited tumor growth without obvious toxicity. Western blot results showed that nanoparticles altered the levels of p53, p-AKT, and p-AMPK in the tumor tissue. Moreover, cell apoptosis was found in the same area of H&E-stained and TUNEL-stained tumors treated with the nanoparticles. Collectively, this nanoparticle system provides a novel combination drug delivery strategy for treating triple-negative breast cancer.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Therapeutics
·
2023
·Vol. 6
·期 4
·2200304
·
IF 4.6
Dan Zhao,Min Wu,Yanan Tian,Lu Gao,Fu Wang
With the advantages of ferroptosis therapy (FT) in solving the apoptotic resistance of tumors, a smart strategy based on the combination of glucose oxidase (GOx) and ferroptosis-inducing nanoagents is proposed to boost the FT. However, most of the nanoagents remain limited in complex synthesis, poor targeting specificity, and unclarified biological mechanisms. Herein, a multifunctional nanoplatform based on fluorescent apoferritin-gold nanoclusters combined with GOx (AFt-AuNCs@GOx) is designed for tumor-targeted imaging and FT. The results show that AFt-AuNCs@GOx catalyze the generation of toxic ·OH from H 2 O 2 supplied by GOx. Consequently, AFt-AuNCs@GOx induce the enhanced ferroptosis effect in 4T1 cells. Additionally, the transcriptome assay of 4T1 cells identifies the differential expression genes related to ferroptosis process after AFt-AuNCs@GOx treatment. Moreover, with the merit of intrinsic fluorescence, the biodistribution both in vitro and in vivo of AFt-AuNCs@GOx can be effectively visualized. In vivo evidences reveal that AFt-AuNCs@GOx have the desired efficacy of FT and excellent biosafety. Overall, the AFt-AuNCs@GOx nanoplatform offer remarkable advantages in simple architecture, fluorescent imaging, precise targeting, and tumor inhibition. The exploration of the ferroptosis effect and biological mechanisms of AFt-AuNCs@GOx, as well as its application in tumor therapy, can introduce a new insight into the field of ferroptotic nanomedicine.
研究领域:
纳米技术
·
癌症治疗
·
分子生物学
·
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）