Asian Journal of Pharmaceutical Sciences
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2024
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IF 10.7
Xianglei Fu,Yanbin Shi,Zili Gu,Hengchang Zang,Lian Li,Qingjie Wang,Yongjun Wang,Xiaogang Zhao,Hang Wu,Shengnan Qiu,Yankun Zhang,Jiamin Zhou,Xiangqin Chen,Hua Shen,Guimei Lin
Despite standard treatment for non-small cell lung cancer (NSCLC) being surgical resection, cancer recurrence and complications, such as induction of malignant pleural effusion (MPE) and significant postoperative pain, usually result in treatment failure. In this study, an alginate-based hybrid hydrogel (SOG) is developed that can be injected into the resection surface of the lungs during surgery. Briefly, endoplasmic reticulum-modified liposomes (MSLs) pre-loaded with the signal transducer and activator of transcription 3 (STAT3) small interfering RNA and lidocaine hydrochloride are encapsulated in SOG. Once applied, MSLs strongly downregulated STAT3 expression in the tumor microenvironment, resulting in the apoptosis of lung cancer cells and polarization of tumor-associated macrophages towards the M1-like phenotype. Meanwhile, the release of lidocaine hydrochloride (LID) was beneficial for pain relief and natural killer cell activation. Our data demonstrated MSL@LID@SOG not only efficiently inhibited tumor growth but also potently improved the quality of life, including reduced MPE volume and pain relief in orthotopic NSCLC mouse models, even with a single administration. MSL@LID@SOG shows potential for comprehensive clinical management upon tumor resection in NSCLC, and may alter the treatment paradigms for other cancers.
研究领域:
肿瘤学
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药理学
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生物医学工程
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免疫疗法
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
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2021
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IF 8.947
Kaipei Luo,Yi Gao,Shaoping Yin,Yawen Yao,Hua Yu,Guangji Wang,Juan Li
Metastasis is one of the major causes of mortality in patients suffering from breast cancer. The signal transducer and activator of transcription 3 (STAT3) is closely related to cancer metastasis. Herein, a multifunctional nanocomplex was developed to simultaneously deliver paclitaxel (PTX) and STAT3 siRNA (siSTAT3) to inhibit tumor growth and prevent metastasis of breast cancer cells. PTX was encapsulated into the synthesized polyethyleneimine-polylactic acid-lipoic acid (PPL) micelle through hydrophobic interaction, while siSTAT3 was condensed onto polyethyleneimine through electrostatic interaction . The surface charge of the drug-loaded nanocomplex ( siSTAT3 PPL PTX ) was then converted to negative by coating with hyaluronic acid (HA). The multifunctional nanocomplex (HA/ siSTAT3 PPL PTX ) effectively entered CD44-overexpressed 4T1 cells via an active targeting mechanism. HA shell was degraded by the concentrated hyaluronidase in the endo/lysosome and the rapid drug release was triggered by the redox micro-environment of cytoplasm. Moreover, HA/ siSTAT3 PPL PTX showed enhanced cytotoxicity against tumor cells due to a synergistic effect of PTX and siSTAT3. The effective inhibition of tumor metastasis was confirmed by in vitro cell migration and invasion in 4T1 cells. More importantly, a superior antitumor efficacy was observed in orthotopic 4T1 tumor-bearing mice, with no side effects in major organs, and the lung metastasis was strongly inhibited in 4T1 metastasis model. In conclusion, the multifunctional nanocomplex provides a versatile platform for efficient treatment of metastatic cancer through tumor-targeted chemo-gene combined therapy. Statement of significance Metastasis is one of the major causes of mortality in patients suffering from breast cancer. The signal transducer and activator of transcription 3 (STAT3) is closely related to cancer metastasis. In this study, a multifunctional nanocomplex co-loaded with paclitaxel (PTX) and STAT3 siRNA was constructed and characterized. The co-delivery system exhibited active tumor targeting, effective endo/lysosomal escape, and rapid intracellular drug release. Both in vitro and in vivo studies indicated that the nanocomplex could lead to superior tumor growth inhibition, as well as metastasis suppression by silencing expression of STAT3 and p-STAT3. This present study implies that the nanocomplex could be a potential platform for targeted treatment of metastatic cancer through chemo-gene combined therapy.
研究领域:
癌症研究
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纳米技术
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药学
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分子生物学
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Biomaterials Science
·
2023
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IF 6.6
Zixu Liu,Linxuan Zhao,Yupeng Feng,Qingqing Wang,Nan Dong,Yu Zhang,Tian Yin,Haibing He,Xing Tang,Jingxin Gou,Li Yang
Cancer vaccine-based immunotherapy has great potential; however, vaccine has been hindered by the immunosuppressive tumor microenvironment (TME). In this study, dual-responsive PEG-lipid polyester nanoparticles (PEG BR647-NP) for tumor-targeted delivery were proposed. PEG BR647-NP containing model tumor associated antigen (TAA) OVA and signal transduction and activator of transcription 3 (STAT3) siRNA were delivered to tumor. PEG BR647-NP was internalized by tumor associated dendritic cells (TADCs), where TAA and siRNA were released into cytoplasm via endo/lysosome escape effect. The released OVA was presented by the major histocompatibility complex class I to activate T cells, the released STAT3 siRNA acted to relieve TADCs dysfunction, promote TADCs maturation, improve antigen-presenting ability, and enhance anticancer T cell immunity. Meanwhile, PEG BR647-NP was ingested by tumor cells, and could kill tumor cells by the pro-apoptosis effect of STAT3 siRNA. Moreover, PEG BR647-NP could reduce the proportion of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in tumors and abrogate immunosuppression. The integration of relieved TADCs dysfunction, promoted TADCs maturation, enhanced antigen cross-presentation, abrogated immunosuppression, and improved pro-apoptosis effect can boost the vaccination for tumor immunotherapy. Thus, PEG BR647-NP efficiently delivered vaccine and STAT3 siRNA to tumor, and modulated immunosuppressive TME, provided better antitumor effects.
研究领域:
癌症免疫疗法
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纳米技术
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分子生物学
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免疫学
✓ 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）