LASERS IN MEDICAL SCIENCE
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2025
·Vol. 40
·期 1
·1-11
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IF 2.4
Ma Dan,Lu Huixiang,Zhang Hai,Liao Anru,Peng Qianrong,Yang Min
Hypoxia poses a significant challenge to the efficacy of photodynamic therapy (PDT) for cancer treatment. This study aims to design and synthesize PEGylated liposomes encapsulating MnO₂, indocyanine green (ICG), and H-chain ferritin (HFn) to potentially address hypoxia and enhance the therapeutic outcomes of PDT. PEGylated liposomes (ICG/MnO₂-HFn-mPEG-DSPE-Lip) were constructed with a rod-like structure, incorporating MnO₂ as a hypoxia-modulating agent and ICG as a photosensitizer. The drug loading capacity, stability and safety of liposomes were characterized. Singlet oxygen quantum yield (Φ Δ ) was measured under simulated tumor microenvironment conditions. In vitro phototoxicity was evaluated using A549 human lung adenocarcinoma cells. Liposomes have a high drug loading capacity, good biocompatibility and good long-term stability. Under tumor-simulated conditions, Φ Δ was significantly improved, increasing from 0.210 for free ICG to 0.507. The liposomes demonstrated remarkable phototoxic effects on A549 cells (90.5% cell death under combined PDT/PTT vs. 15% for free ICG). This nanoplatform proposes a novel strategy to overcome hypoxia-induced PDT resistance, and the enhanced efficacy may be attributed to the increased oxygen supply mediated by MnO 2 carried by HFn. These findings provide important insights for the development of next-generation therapeutic systems targeting tumor hypoxia.
研究领域:
药学
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肿瘤学
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生物医学工程
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF REFRACTORY METALS & HARD MATERIALS
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2025
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IF 4.6
Zhongyou Que,Xingyu Li,Lin Zhang,En Mei,Chenguang Guo,Haishen Sun,Junming Liu,Mingli Qin,Gang Chen,Xuanhui Qu
The in-situ synthesis of finely dispersed second phases with high melting points and thermal stability is an effective strategy to address the high cost, inadequate high-temperature performance, and reduced thermal conductivity of tungsten‑rhenium (W Re) alloys. In this study, we employed a novel nitridation-denitridation (NDN) process to synthesize W-10Re-HfN nano powder, in-situ synthesizing nano HfN particles to strengthen and toughen the W Re alloy. Compared to W 10Re, the hardness of W-10Re-2HfN increased significantly from 604 HV to 977 HV, the compressive strength was improved from 1366 MPa to 2181 MPa, and fracture strain increased from 3.6 % to 32 %. Statistical results indicate that HfN particles within the grains or with sizes below ∼36 nm exhibit completely coherent interfaces with the W Re matrix. By combining in-situ synthesis of nitrides with a two-step sintering process, we successfully retained 63 % of HfN particles within the grains and controlled the average particle size of HfN particles at the grain boundaries to be 36 nm, thereby enhancing grain boundary strengthening and coherent interface strengthening. This study innovatively incorporates finely dispersed and highly stable nitrides into W Re alloys through in-situ doping, offering a novel strategy for reinforcing refractory metals.
研究领域:
材料科学
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机械工程
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DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2025
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IF 5.6
Yuan Fan,Yuxiang Liu,Liujiao Wang,Huashan Xu,Lele Yu,Yue Lang,Huafei Li,Fuxue Chen,Shini Feng
Protein hydrolysis-targeted chimeras (PROTACs) are heterobifunctional molecules designed for the selective degradation of target proteins. MS4078, a novel PROTAC, shows promise for treating ALK-positive non-small cell lung cancer (NSCLC), yet its clinical efficacy is hindered by suboptimal tumor targeting and off-target toxicities. To enhance its therapeutic profile, we developed human heavy chain ferritin (HFN) as a targeted delivery system, leading to the creation of HFN@MS4078 nanocages. Prepared via passive loading, HFN@MS4078 achieved a drug loading capacity of 178 molecules per nanocage with a HFN recovery rate of 70.1 %. The nanocages exhibited a rapid release profile under lysosomal conditions (pH 5.0), with approximately 80 % drug release after 60 h, while maintaining over 80 % stability at physiological pH 7.4. In vitro, HFN@MS4078 was actively internalized into lysosomes via TfR1 receptor binding, resulting in a 2.7–2.8 times reduction in IC 50 values compared to free MS4078. Furthermore, HFN@MS4078 significantly decreased the expression levels of ALK, p-ALK, p-AKT, and p-ERK in NCI-H2228 and NCI-H3122 cell lines. In vivo, HFN@MS4078 substantially reduced tumor volume and prolonged survival while exhibiting negligible systemic toxicity. These results suggest that HFN@MS4078 represents a promising strategy for targeted therapy in ALK-positive NSCLC, enhancing therapeutic efficacy while minimizing systemic toxicity.
研究领域:
肿瘤学
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药学
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纳米技术
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分子生物学
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药物递送
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生物医学工程
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-17
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IF 10.2
Wu Xinzhou,Jiao Zhouguang,Zhang Junying,Li Feng,Li Yuhua
Background Currently, high doses of cytarabine arabinoside (Ara-C)-based combined chemotherapy are commonly used in acute myeloid leukemia (AML) therapy, but severe adverse effects and poor suppression effects in leukemia cells limit the clinical therapeutic efficiency of Ara-C-based chemotherapy due to a lack of targeting selectivity. To improve the therapeutic effect of Ara-C in AML, here, since we confirmed that transferrin receptor 1 (TFRC) expression in AML cells was constant, we generated Ara-C@HFn by encapsulating free Ara-C into self-assembled heavy ferritin chain (HFn, the ligand of TFRC) nanocages.Results The analysis of clinically relevant data suggested that the high expression levels of TFRC from AML cells would not decrease significantly after treatment with Ara-C. Ara-C@HFn can be efficiently internalized by leukemia cells, showing stronger cytotoxic effects in vitro and reducing the burden of leukemia in AML mice more effectively in vivo than free Ara-C. Ara-C@HFn treatment showed no acute toxicity in visceral organs of mice. Moreover, the analysis of clinically relevant data also suggested that there are several drugs (such as tamibarotene and ABT199) that would not cause significant expression down-regulation of TFRC in AML cells (after treatment).Conclusion The above results suggested that TFRC can be used as a constant and effective target for drug targeting delivery of AML cells. Thus Ara-C@HFn treatment can become a safe and efficient strategy for AML therapy by specifically delivering Ara-C to AML cells. Besides, the HFn nanocages are promising for improving antineoplastic effect of other AML-related therapy drugs that do not cause downregulated expression of TFRC in AML cells.Graphical Abstract
研究领域:
肿瘤学
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药理学
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分子生物学
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血液学
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DOI
PubMed
高影响因子
Nanoscale
·
2022
·Vol. 14
·期 17
·6449-6464
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IF 8.307
Ziwei Yuan,Bin Wang,Yilong Teng,William Ho,Bin Hu,Kofi Oti Boakye-Yiadom,Xiaoyang Xu,Xue-Qing Zhang
Gene therapy holds tremendous potential for the treatment of incurable brain diseases including Alzheimer's disease (AD), stroke, glioma, and Parkinson's disease. The main challenge is the lack of effective gene delivery systems traversing the blood–brain barrier (BBB), due to the complex microvessels present in the brain which restrict substances from the circulating blood passing through. Recently, increasing efforts have been made to develop promising gene carriers for brain-related disease therapies. One such development is the self-assembled heavy chain ferritin (HFn) nanoparticles (NPs). HFn NPs have a unique hollow spherical structure that can encapsulate nucleic acid drugs (NADs) and specifically bind to cancer cells and BBB endothelial cells (BBB ECs) via interactions with the transferrin receptor 1 (TfR1) overexpressed on their surfaces, which increases uptake through the BBB. However, the gene-loading capacity of HFn is restricted by its limited interior volume and negatively charged inner surface; therefore, these drawbacks have prompted the demand for strategies to remould the structure of HFn. In this work, we analyzed the three-dimensional (3D) structure of HFn using Chimera software (v 1.14) and developed a class of internally cationic HFn variants (HFn+ NPs) through arginine mutation on the lumenal surface of HFn. These HFn+ NPs presented powerful electrostatic forces in their cavities, and exhibited higher gene encapsulation efficacy than naive HFn. The top-performing candidate, HFn2, effectively delivered siRNA to glioma cells after traversing the BBB and achieved the highest silencing efficacy among HFn+ NPs. Overall, our findings demonstrate that HFn+ NPs obtained by this genetic engineering method provide critical insights into the future development of nucleic acid delivery carriers with BBB-crossing ability.
研究领域:
生物医学工程
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分子生物学
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神经科学
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药学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Liqiao Zhang,Xinyu Cao,Jiayi Chen,Yanyan Dong,Wenwen Chen,Yu Gao,Jingjing Guo,Haiqin Huang
Multidrug resistance (MDR) poses a significant impediment to the efficacy of chemotherapy in clinical settings. Despite Paclitaxel (PTX) being designated as the primary pharmaceutical agent for treating recurrent and metastatic breast cancer, the emergence of PTX resistance frequently results in therapeutic shortcomings, representing a substantial obstacle in clinical breast cancer management. In response, we developed a delivery system exhibiting dual specificity for both tumors and mitochondria. This system facilitated the sequential administration of small interfering B-cell lymphoma-2 (siBcl-2) and PTX to the tumor cytoplasm and mitochondria, respectively, with the aim of surmounting PTX resistance in tumor cells through the activation of the mitochondrial apoptosis pathway. Notably, we employed genetic engineering techniques to fabricate a recombinant ferritin containing the H-subunit (HFn), known for its tumor-targeting capabilities, for loading siBcl-2. This HFn-siBcl-2 complex was then combined with positively charged Triphenylphosphine-Liposome@PTX (TL@PTX) nanoparticles (NPs) to formulate HFn/siBcl-2@TL/PTX. Guided by HFn, these nanoparticles efficiently entered cells and released siBcl-2 through the action of triphenylphosphine (TPP)-mediated “proton sponge,” thereby precisely modulating the expression of Bcl-2 protein. Simultaneously, PTX was directed to the mitochondria through the accurate targeting of TL@PTX, synergistically initiating the mitochondrial apoptosis pathway and effectively suppressing PTX resistance both in vitro and in vivo . In conclusion, the development of this dual-targeting delivery system presents a promising therapeutic strategy for overcoming PTX resistance in the clinical treatment of breast cancer.
研究领域:
肿瘤学
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药学
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分子生物学
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纳米技术
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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）