CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Yichen Li,Yi Cao,Hao Bai,Luwei Zhang,Baiqiu Chen,Chengfan Wu,Qi Shuai,Yunfeng Yan
The application of mRNA-based therapies has gained significant attention in recent years, with lipid nanoparticles (LNPs) emerging as key delivery vehicles. However, challenges remain in optimizing delivery efficiency and targeting tissues beyond the liver, particularly for immunotherapy. In this study, we constructed novel lipids with disulfide bonds in the linkers and utilized the redox responsiveness of these bonds in the reductive microenvironment of tumor or immune cells to enable robust splenic mRNA delivery and potent cancer immunotherapy. A library of 119 lipids was synthesized by conjugating hydrophilic amines, disulfide-containing linkers, and hydrophobic amines via sequential aza-Michael addition. In vitro screening identified lipids with longer, branched hydrophobic tails, particularly 2C10, as leading carriers for mRNA delivery. Compared to conventional LNPs without disulfide linkers, disulfide-containing LNPs showed smaller size, higher mRNA binding, and enhanced mRNA release in the presence of GSH, with predominantly spleen-targeted in vivo delivery. Encapsulation with OVA mRNA promoted CD4 + and CD8 + T cell differentiation, leading to significant tumor regression in a melanoma mouse model. These findings highlight the potential of redox-responsive LNPs for targeted mRNA delivery and cancer immunotherapies.
研究领域:
生物技术
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药理学
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免疫学
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
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2023
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IF 9.5
Ping Chen,Xi He,Yue Hu,Xiao-Li Tian,Xiao-Qi Yu,Ji Zhang
In recent years, the application of mRNA vaccine-based tumor immunotherapy invigorated anti-tumor therapy. However, the low efficiency of mRNA delivery and the lack of targeting ability in vivo are the major obstacles to achieving highly efficient immunotherapy. In this work, we report a chemical library of amphiphilic carbon dots (ACDs) and the synthesized ACDs were applied to mRNA delivery, bio-imaging, and tumor immunotherapy. The ACDs can smoothly bind with mRNA to form ACDs@mRNA nanocomplexes, and the fluorescent properties of the ACDs afforded the nanoparticles with bio-imaging ability. By screening of the ACDs, O12-Tta-CDs were found to have optimal mRNA transfection efficiency and the ability of spleen-targeted delivery. In addition, O12-Tta-CDs can well transfect the immune cells and promote the maturation and antigen presentation of bone marrow-derived dendritic cells (BMDCs). Furthermore, O12-Tta-CDs@OVA-mRNA was successfully applied to inhibit tumor growth, and more specific T-cell infiltration was observed in spleen and tumors of mice after treatment in the E.G7-OVA tumor model. Besides, O12-Tta-CDs@OVA-mRNA also achieved a good therapeutic effect in tumor recurrence inhibition and tumor prophylactic experiments. This study provided a new direction for the design of mRNA vectors, which is promising in tumor immunotherapy.
研究领域:
生物医学工程
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免疫学
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
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2016
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IF 5.228
Yufei Ma,Haiming Wang,Dan Yan,Yanquan Wei,Yuhua Cao,Peiwei Yi,Hailu Zhang,Zongwu Deng,Jianwu Dai,Xiangtao Liu,Jianxun Luo,Zhijun Zhang,Shiqi Sun,Huichen Guo
Canine parvovirus (CPV) is a highly contagious infectious virus, whose infectious mechanism remains unclear because of acute gastroenteritis and the lack of an efficient tool to visualize the virus in real time during virology research. In this study, we developed an iron oxide nanoparticle supported by graphene quantum dots (GQD), namely, FeGQD. In this composite material, GQD acts as a stabilizer; thus, vacancies are retained on the surface for further physical adsorption of the CPV VP2 protein. The FeGQD@VP2 nanocomposite product showed largely enhanced colloidal stability in comparison with bare FeGQD, as well as negligible toxicity both in vitro and in vivo. The composite displayed high uptake into transferrin receptor (TfR) positive cells, which are distinguishable from FeGQD or TfR negative cells. In addition, the composite developed a significant accumulation in spleen rather than in liver, where bare FeGQD or most iron oxide nanoparticles gather. As these evident targeting abilities of FeGQD@VP2 strongly suggested, the biological activity of CPV VP2 was retained in our study, and its biological functions might correspond to CPV when the rare splenic targeting ability is considered. This approach can be applied to numerous other biomedical studies that require a simple yet efficient approach to track proteins in vivo while retaining biological function and may facilitate virus-related research.
研究领域:
病毒学
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纳米医学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2025
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IF 8.2
Chao Liu,Yuhao Jiang,Wenliang Xue,Jinyu Liu,Zihao Wang,Jianhong Luo,Xinsong Li
Lipid nanoparticles (LNP) have shown great promise in clinical applications for delivering mRNA. Targeted delivery of mRNA to particular tissues or organs is essential for precise therapeutic outcomes and minimized side effects in various disease models. However, achieving targeted delivery beyond the liver is a challenge based on current LNP formulations. In this report, we synthesized four ionizable cholesterol analogs by attaching two tertiary amine groups onto the head of a cholesterol-like structure and incorporated them as a fifth component into conventional commercial LNPs based on ALC-0315 or SM-102. Selective targeting delivery of mRNA is achieved by adjusting the proportion of the fifth component in the LNP. Specifically, a spleen-targeted 0315-Ergo-40% formulation demonstrated an impressive 95% delivery efficiency, while a lung-targeted 102-Sito-40% formulation achieved up to 78%. Moreover, when this strategy is applied to a self-developed ionizable lipid named U-101 instead of ALC-0315 or SM-102, the targeting delivery efficiencies to the spleen and lungs reach 96 and 71%, respectively. Multiple assessments suggest that inclusion of the fifth component does not compromise LNP stability, as indicated by consistent particle size, polydispersity index (PDI), and encapsulation efficiency. Furthermore, the test results of liver and kidney function and immunogenicity reveal no increase of toxicity in vivo following the introduction of the fifth component. Additional studies on in vitro cytotoxicity, lysosomal escape, and cellular transfection efficiency confirm that the fifth component does not diminish delivery performance. Taken together, the incorporation of ionizable cholesterol analogs leads to targeting of LNP delivery, which features strong organ selectivity, high safety, and suitability for further evaluation.
研究领域:
纳米技术
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药学科学
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分子生物学
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治疗学
✓ 已验证
DOI
PubMed
高影响因子
ACS Nano
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2024
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IF 15.8
Zijin Luo,Yi Lin,Yanan Meng,Mengyao Li,Hongyu Ren,Haoping Shi,Qiang Cheng,Tuo Wei
The successful application of mRNA vaccines in preventing and treating infectious diseases highlights their potential as therapeutic vaccines for cancer treatment. However, unlike infectious diseases, effective antitumor therapy, particularly for solid tumors, necessitates the activation of more powerful cellular and humoral immunity to achieve clinical efficacy. Here, we report a spleen-targeted mRNA vaccine (Mn@mRNA-LNP) designed to deliver tumor antigen-encoding mRNA and manganese adjuvant (Mn2+) simultaneously to dendritic cells (DCs) in the spleen. This delivery system promotes DC maturation and surface antigen presentation and stimulates the production of cytotoxic T cells. Additionally, Mn2+ codelivered in the system serves as a safe and effective immune adjuvant, activating the stimulator of interferon genes (STING) signaling pathway and promoting the secretion of type I interferon, further enhancing the antigen-specific T cell responses. Mn@mRNA-LNP effectively inhibits tumor progression in established melanoma and colon tumor models as well as in a model of tumor recurrence after resection. Notably, the combination of Mn@mRNA-LNP with immune checkpoint inhibitors further enhances complete tumor suppression and prolonged the overall survival in mice. Overall, this “All-in-One” mRNA vaccine significantly boosts antitumor immunity responses by improving spleen targeting and immune activation, providing an attractive strategy for the future clinical translation of therapeutic mRNA vaccines.
研究领域:
癌症免疫治疗
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疫苗开发
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Yiming Wang,Chen Wang,Yuan Lu
Nucleic acids have attracted increasing attention as drugs due to their fascinating advantages, such as long-term efficacy and ease of preparation compared to proteins. The nucleic acid therapy relies heavily on delivery vectors, which can prevent the degradation of nucleic acids while assisting them in cellular internalization. However, commonly used nonviral vector liposomes easily accumulate in the liver, which can limit their application in extrahepatic diseases. Herein, a potential spleen targeting vector for nucleic acids is developed based on the metal–organic frameworks. The plasmids are encapsulated inside the nanoscale zeolitic imidazolate framework (ZIF) via coprecipitation. The co-encapsulation of the cationic polymer poly(ether imide) (PEI) and the stabilizer polyvinylpyrrolidone (PVP) can significantly improve particle dispersion and stability. The prepared nanoparticles allow efficient transfection in vitro, mainly through clathrin-mediated and caveolae-mediated endocytosis. The biodistribution in mice shows that 46% of the nanoparticles accumulate in the spleen, which is much higher than that of the liposomes. The vector can successfully deliver plasmids to extrahepatic organs for protein synthesis and even induce an immune response. The elaborate ZIF-based nanoparticle may offer a new route for extrahepatic, especially spleen targeting delivery for the nucleic acids.
研究领域:
药理学
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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
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