CHEMICAL ENGINEERING JOURNAL
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2024
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IF 13.3
Faisal Raza,Liangdi Jiang,Shulei Zhang,Hajra Zafar,Yujiao Qiu,Jing Su,Mingfeng Qiu
The efficient eradication of tumor cells remains a critical challenge in the realm of liver cancer therapies. The combination of chemotherapy and immunotherapy holds more significant potential for improving treatment efficacy. However, the effectiveness of immunotherapy is mainly impeded by the high activity of indoleamine 2,3-dioxygenase (IDO), which creates an immunosuppressive tumor microenvironment via robust proliferation of immunosuppressive T regulatory cells (T regs ) and inhibition of cytotoxic T lymphocytes (CTLs). Herein, we developed SR-ATO-ASIV@NS, a liver cancer-targeting peptide (SP94) modified RBCM-coated biomimetic nanosuspension. This innovative formulation incorporates the chemotherapeutic agent arsenic trioxide (ATO) and the immunomodulator astragaloside IV (AS-IV) as IDO inhibitor for the combined chemoimmunotherapy of liver cancer. The SR-ATO-ASIV@NS increased the solubility of both ATO and AS-IV and displayed excellent stability and exhibited high drug-loading efficiency, rendering it suitable for efficient dual drug delivery. Furthermore, this biomimetic nanosuspension efficiently evaded immune response and showed specific uptake in liver cancer cells via SP94 receptor-mediated endocytosis. The remarkable pharmacokinetic profile, characterized by prolonged blood circulation, enhanced the in vivo anti-tumor efficacy in H22 tumor bearing mice through the synergistic action of the dual drugs. On one hand, the released ATO resulted in excessive reactive oxygen species (ROS) generation, which stimulated the induction of apoptosis pathways via Bax/Bcl-2 and caspase mechanism. While on the other hand, AS-IV effectively blocked the IDO activity and hinders the production of T regs within the tumor microenvironment. Consequently, the reduced T regs population fosters the proliferation of CTLs, alleviating ITM and intensifying the immunotherapeutic response for the efficient killing of cancer cells. Additionally, the successful inhibition of liver cancer metastasis to the lungs and robust increase in T memory cells further boosted the anti-tumor therapeutic efficacy of SR-ATO-ASIV@NS. In summary, SR-ATO-ASIV@NS represents a novel and scientifically sophisticated strategy in targeted biomimetic nanotherapeutics. This approach not only enhances site-specific drug delivery but also showcases promising potential for advancing the field of combined chemoimmunotherapy for liver cancer.
研究领域:
癌症研究
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药学
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纳米技术
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免疫疗法
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化疗
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药物递送系统
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产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
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2022
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IF 5.589
Wenyuan Zhang,Bo Han,Chuya Gao,Xiaoying Liu,Yanbo Peng,Chen Gong,Dandan Hu,Na Wang,Shukun Tang,Beining Zhang,Man Zhao,Haisheng Peng
Hepatocellular carcinoma (HCC) is a most common primary liver cancer among the most deadly malignancies. Selectively killing the cancer cells within the liver urgently requires the novel treatment strategies. The combination of sonodynamic therapy (SDT) and chemotherapy based on the nanotechnology have achieved some achievements in the HCC treatments. However, off-targeting drug delivery to healthy cells and the hypoxic microenvironment in the solid tumors frustrate the efforts to the combined strategy. The hypoxic microenvironment restrains the generation of ROS , leading to the decreased effects of SDT. To improve the clinical outcomes of chemo/SDT strategy, we created a novel oxygen self-enriched active targeted nanovesicle (ICG-DOX NPs/ [email protected] ). SP94 peptide could enhance the selectivity of the nanovesicles to liver tumor cells rather than normal liver cells. Besides, an oxygen carrier, perfluorohexanes (PFH), was co-loaded into liposomes to increase the oxygen level in tumor tissue, thus improving the effects of SDT. The in vivo studies showed that the ICG-DOX NPs/ [email protected] combined with the external US stimulation significantly inhibited effects on tumor growth. Therefore, this novel oxygen self-enriched chemo/SDT nanocomposites represents a proof-of-concept liver tumor treatment strategy.
研究领域:
癌症生物学
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纳米医学
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治疗递送
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生物医学工程
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DOI
PubMed
高影响因子
Current Drug Delivery
·
2026
·Vol. 23
·期 6
·681-697
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IF 3.1
Lin Jing,Simei Luo,Ye Gan,Lili Li,Haotian Wu,Jiajia Zhang,Xu Liu,Mingqing Yuan
Introduction The toxicity of nontargeted chemotherapy hinders liver cancer treatment. This study developed dual-peptide (SP94/TAT) co-modified liposomes (SP94/TAT-DOX/DTX-LPs) for enhanced targeting and efficacy. Methods Liposomes encapsulating docetaxel (DTX) and doxorubicin (DOX) were prepared via film dispersion/ammonium sulfate gradient using DSPE-PEG, lecithin, and cholesterol. SP94 (targeting) and TAT (penetrating) peptides were conjugated via organic phase reaction/insertion. Their physicochemical properties, encapsulation efficiency, stability, drug release, and in vitro antitumor activity were evaluated. Results Optimized SP94/TAT-DOX/DTX-LPs were spherical (119.6 ± 4.1 nm; PDI 0.161 ± 0.006; zeta -9.84 ± 1.54 mV), and their encapsulation efficiency was high (DOX: 92.97 ± 1.73%; DTX: 80.33 ± 0.96%). Stability was confirmed at 4 °C for 30 days (PDI < 0.2, size change < 10%) and in 50% fetal bovine serum (FBS) for 24 hours (transmittance > 90%). Sustained release showed 68.2 ± 3.5% (DTX) and 74.8 ± 2.9% (DOX) cumulative release at 48h (PBS pH 7.4). In vitro, SP94/TAT-DOX-LPs showed 2.3-fold higher HepG2 cellular uptake versus single-modified liposomes (p<0.001), with minimal LO2 uptake. Cytotoxicity assays revealed a 3.11-fold lower IC50 (0.096 ± 0.026 μg/mL) versus unmodified liposomes (0.299 ± 0.103 μg/mL). Apoptosis was significantly higher (39.5% in HepG2) than in single-modified formulations (20.55–26.74%). Discussion SP94/TAT-LPs enable dual-stage targeting: SP94 targets liver cancer cells, and TAT enhances penetration, significantly improving in vitro antitumor activity. Study limitations include sole in vitro validation (HepG2/LO2), small sample size (n=3), parameter variability, and lack of in vivo data on targeting, pharmacokinetics, and toxicity. Conclusion SP94/TAT-DOX/DTX-LPs achieved effective dual-stage targeting and synergistic cytotoxicity. High encapsulation, stability, and sustained release support their potential as a targeted platform for liver cancer therapy, reducing off-target toxicity.
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DOI
高影响因子
Journal of Materials Chemistry B
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2024
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IF 6.1
Wangbo Jiao,Nana Wen,Siyao Wang,Guxiang Zhou,Qiaoyi Lu,Zijun Su,Xinxin Wang,Shuwei Hu,Youbang Xie,Nan Zhang,Xiaoli Liu
Magnetic nanomaterial-mediated magnetic hyperthermia is a localized heating treatment modality that has been applied to treat aggressive cancer in clinic. In addition to being taken up by tumor cells to function in cancer therapy, magnetic nanomaterials can also be internalized by immune cells in the tumor microenvironment, which may contribute to regulating the anti-tumor immune effects. However, there exists little studies for the distribution of magnetic nanomaterials in different types of cells within tumor tissue. Herein, ferrimagnetic vortex-domain iron oxide nanorings (FVIOs) with or without the liver-cancer-targeting peptide SP94 have been successfully synthesized as a model system to investigate the effect of surface modification of FVIOs (with or without SP94) on the distribution of tumor cells and different immune cells in hepatocellular carcinoma (HCC) microenvironment of mouse. The distribution ratio of FVIO-SP94s in tumor cells was 1.3 times more than that of FVIOs. Immune cells in the liver tumor microenvironment took up fewer FVIO-SP94s than FVIOs. In addition, myeloid cells were found to be much more amenable than lymphoid cells in terms of their ability to phagocytose nanoparticles. Specifically, the distributions of FVIOs/FVIO-SP94s in tumor-associated macrophages, dendritic cells, and myeloid-derived suppressor cells were 13.8%/12%, 3.7%/0.9%, and 6.3%/1.2%, respectively. While the distributions of FVIOs/FVIO-SP94s in T cells, B cells, and natural killer cells were 5.5%/0.7%, 3.0%/0.7%, and 0.4%/0.3%, respectively. The results described in this article enhances our understanding of the distribution of nanomaterials in the tumor microenvironment and provides a strategy to rational design magnetic hyperthermia agent for effectively regulating anti-tumor immune effects.
研究领域:
纳米技术
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癌症研究
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免疫学
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材料科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
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2026
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IF 4.9
Gan Qiu,Xinting Zhao,Yu Long,Lisheng Wang
In this study, we developed a multifunctional nanodelivery system to achieve precise treatment of hepatocellular carcinoma (HCC). Previous work by our group synthesized a matrine derivative A6, which exhibits potent antitumor activity; however, its further development and application have been limited by issues such as poor solubility and stability. Meanwhile, the clinical use of the chemotherapeutic agent doxorubicin (DOX) is restricted by its cardiotoxicity. To address these challenges, we designed a dual-drug-loaded liposomal system (SP94/BR2–A6/DOX–LP) that encapsulates both A6 and DOX, demonstrating high drug loading capacity and encapsulation efficiency. Furthermore, by functionalizing the liposome surface with SP94 and BR2 peptides enhanced tumor their targeting and therapeutic efficacy. Our findings indicate that A6 and DOX act synergistically against HCC. The dual-targeting strategy mediated by SP94 and BR2 promotes precise accumulation of the liposomes in hepatocellular carcinoma cells, significantly improving antitumor outcomes. This multifunctional nanodelivery system significantly enhances both the targeting efficiency and therapeutic efficacy of the loaded drugs, thereby paving the way for a promising new strategy in the precision treatment of hepatocellular carcinoma.
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高影响因子
ACS Applied Materials & Interfaces
·
2024
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IF 8.3
Hongyu Tang,Zhijie Wang,Haoyang Hao,Weixian Luo,Jingru Yang,Mengyao Li,Mingxin Yang,Ziteng Chen,Ruyu Yan,Hao Li,Fan Hu,Haojun Liang,Qiuyang Liu,Linwen Lv,Junhui Zhang,Wenxi Su,Ranran Chen,Kui Chen,Ya-nan Chang,Meng Wang,Lingna Zheng,Xuesong Feng,Juan Li,Gengmei Xing
Nanocarriers have been researched comprehensively for the development of novel boron-containing agents in boron neutron capture therapy (BNCT). We designed and synthesized a multifunctional mesoporous silica nanoparticle (MSN)-based boron-containing agent. The latter was coated with a lipid bilayer (LB) and decorated with SP94 peptide (SFSIIHTPILPL) on the surface as SP94-LB@BA-MSN. The latter incorporated boric acid (BA) into hydrophobic mesopores, coated with an LB, and modified with SP94 peptide on the LB. SP94-LB@BA-MSN enhanced nano interface tumor-targeting ability but also prevented the premature release of drugs, which is crucial for BNCT because adequate boron content in tumor sites is required. SP94-LB@BA-MSN showed excellent efficacy in the BNCT treatment of HepG-2 cells. In animal studies with tumor-bearing mice, SP94-LB@BA-MSN exhibited a satisfactory accumulation at the tumor site. The boron content reached 40.18 ± 5.41 ppm in the tumor site 4 h after injection, which was 8.12 and 15.51 times higher than those in mice treated with boronated phenylalanine and those treated with BA. For boron, the tumor-to-normal tissue ratio was 4.41 ± 1.13 and the tumor-to-blood ratio was 5.92 ± 0.45. These results indicated that nanoparticles delivered boron to the tumor site effectively while minimizing accumulation in normal tissues. In conclusion, this composite (SP94-LB@BA-MSN) shows great promise as a boron-containing delivery agent for the treatment of hepatocellular carcinoma using BNCT. These findings highlight the potential of MSNs in the field of BNCT.
研究领域:
纳米技术
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癌症治疗
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材料科学
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药学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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