RSC Advances
·
2025
·Vol. 15
·期 15
·11283-11292
·
IF 4.6
Zixin Liang,Xinyi Xu,Ning Wang,Xintao He,Xingzhi Han,Liuqi Sang,Jing Hu,Xiaoping Qian
Colorectal cancer (CRC) remains a major global health challenge, particularly in advanced stages where drug resistance leads to high recurrence rates and poor survival outcomes. This study investigates a novel therapeutic approach combining gambogic acid (GA) with manganese dioxide (MnO2) nanoparticles (MBG NPs) to enhance anti-tumor efficacy in the acidic and hypoxic tumor microenvironment (TME). The development of MBG NPs involved conjugating MnO2 nanosheets with bovine serum albumin (BSA) for effective GA encapsulation, optimizing the delivery of both components. We explored the potential of Mn2+ ions released from MnO2 to synergize with GA to alleviate tumor hypoxia and modulate the TME, thereby improving immune response. In vitro assays demonstrated significant cytotoxicity of MBG NPs against mouse colon cancer cells (CT26 cells), with enhanced apoptosis and elevated reactive oxygen species (ROS) levels. In vivo studies using BALB/c mice showed that treatment with MBG NPs significantly reduced tumor volumes and improved survival rates compared to controls. Additionally, MBG NPs combined with programmed death-1 inhibitor (aPD-1) further augmented therapeutic effects. Histological analyses confirmed tumor necrosis and changes in TME composition, indicating the potential of this synergistic strategy to overcome drug resistance in microsatellite stable (MSS) CRC, inhibit tumor growth and benefit patient survival. These findings highlight the promising application of nanoparticle-based platforms in enhancing immunotherapy outcomes for advanced colorectal cancer.
研究领域:
肿瘤学
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纳米医学
·
免疫学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2017
·
IF 3.649
Yingqi Xu,Shengpeng Wang,Hon Fai Chan,Yuling Liu,Hui Li,Chengwei He,Zeyong Li,Meiwan Chen
Mitochondria are important targets for the intracellular delivery of drugs and DNA. For mitochondria-targeted delivery, a mitochondriotropic molecule, triphenylphosphonium (TPP), was applied to the synthesis of amphiphilic TPP-poly(ethylene glycol)-poly(ε-caprolactone) (TPP-PEG-PCL) polymers. The TPP-PEG-PCL polymer was used to prepare micelles using a solvent evaporation method for the delivery of gambogic acid (GA) (GA-TPP). The micelles were obtained with a favorable particle size of 150.07 ± 11.71 nm and an encapsulation efficiency of 80.78 ± 1.36%, and they displayed homogeneous spherical shapes. The GA-TPP micelles exerted enhanced cytotoxic and pro-apoptotic effect against A549 cells compared to free GA and GA-loaded PEG-PCL (GA-PP) micelles, due to the inhibition of the expression of apoptosis-related proteins and promotion of caspase 3/7 and caspase 9 activity. Notably, the mitochondria-targeting GA-TPP micelles selectively accumulated in the mitochondria, inducing the loss of mitochondrial membrane potential and the release of cytochrome c , thereby achieving improved mitochondria-targeting effects. In conclusion, the GA-TPP micelle system shows great promise for lung cancer treatment by inducing an apoptotic effect via the mitochondrial signaling pathway.
研究领域:
药物学
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材料科学
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肿瘤学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2019
·Vol. 9
·期 47
·27136-27146
·
IF 3.049
Wei Fang,Ya Ji Dai,Ting Wang,Hai Tao Gao,Peng Huang,Juan Yu,He Ping Huang,Dian Lei Wang,Wei Lu Zong
Based on aminated β-cyclodextrin (6-NH2-β-CD)-grafted Fe3O4 and gambogic acid (GA) clathrate complexes, a nanoparticle delivery system was developed with the aim to achieve low irritation, strong targeting, and high bioavailability of a gambogic acid magnetic nanopreparation. 6-NH2-β-CD grafted onto Fe3O4 MNPs was demonstrated by high-resolution transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, zeta potential, and magnetic measurements. The average particle size of the Fe3O4@NH2-β-CD MNPs was 147.4 ± 0.28 nm and the PDI was 0.072 ± 0.013. The encapsulation efficiency, drug loading, zeta potential, and magnetic saturation values of the Fe3O4@NH2-β-CD MNPs were 85.71 ± 3.47%, 4.63 ± 0.04%, −29.3 ± 0.42 mV, and 46.68 emu g−1, respectively. Compared with free GA, the in vitro release profile of GA from Fe3O4@NH2-β-CD MNPs was characterized by two phases: an initial fast release and a delayed-release phase. The Fe3O4@NH2-β-CD MNPs displayed continuously increased cytotoxicity against HL-60 and HepG2 cell lines in 24 h, whereas the carrier Fe3O4@NH2-β-CD MNPs showed almost no cytotoxicity, indicating that the release of GA from the nanoparticles had a sustained profile and Fe3O4@NH2-β-CD MNPs as a tumor tissue-targeted drug delivery system have great potential. Besides, blood vessel irritation tests suggested that the vascular irritation could be reduced by the use of Fe3O4@NH2-β-CD MNPs encapsulation for GA. The t1/2 and the AUC of the Fe3O4@NH2-β-CD@GA MNPs were found to be higher than those for the GA solution by approximately 2.71-fold and 2.42-fold in a pharmacokinetic study, respectively. The better biocompatibility and the combined properties of specific targeting and complexation ability with hydrophobic drugs make the Fe3O4@NH2-β-CD MNPs an exciting prospect for the targeted delivery of GA.
研究领域:
纳米技术
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药学
·
生物医学工程
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癌症研究
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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）