Fluorinated Polyethylenimine and Fluorinated Choline Phosphate Lipids Complex System for Efficient mRNA Delivery to Deep-Seated Tumor Tissues

IF 5.5 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Biomacromolecules Pub Date : 2024-08-12 DOI:10.1021/acs.biomac.4c00625

Shengran Li , Meiying Lv , Weikang Mei , Xifei Yu

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Abstract

Efficiently delivering mRNA to the deep-seated cells of diseased tissues for therapeutic purposes remains a significant challenge. To address this, we leveraged the dual hydrophobic properties of fluorine atoms to conjugate fluorinated polyethylenimine (FPEI) with fluorinated choline phosphate (FCP) lipids. When one adjusted the ratio of N/F atoms to 2/1 and a 15% FCP content, the mRNA@FPEI-FCP carrier was optimized, achieving significant circulation and accumulation in deep tumor regions. Compared to control carriers lacking FCP or FPEI, mRNA@FPEI-FCP exhibited a 3.94-fold increase in tumor targeting and a 3.0-fold increase in deep delivery. Delivery of IL-2 mRNA to 4T1 breast tumors resulted in a tumor inhibition rate of 91.9%, with IL-2 levels reaching 149.2 pg/mL and 12.1% of CD4⁺ cells throughout the tumor, with no abnormal blood indexes. This FPEI and FCP composite delivery system demonstrates potent targeting of mRNA delivery to deep tumor tissues.

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氟化聚乙烯亚胺和氟化磷酸胆碱脂质复合物系统用于向深部肿瘤组织高效递送 mRNA。

如何高效地将 mRNA 运送到病变组织的深层细胞以达到治疗目的，仍然是一项重大挑战。为了解决这个问题，我们利用氟原子的双重疏水特性，将氟化聚乙烯亚胺（FPEI）与氟化磷酸胆碱（FCP）脂质共轭。当调整N/F原子的比例至2/1和15%的FCP含量时，mRNA@FPEI-FCP载体得到了优化，在肿瘤深部区域实现了显著的循环和积累。与缺乏 FCP 或 FPEI 的对照载体相比，mRNA@FPEI-FCP 的肿瘤靶向性提高了 3.94 倍，深部递送提高了 3.0 倍。向4T1乳腺肿瘤递送IL-2 mRNA后，肿瘤抑制率达到91.9%，IL-2水平达到149.2 pg/mL，整个肿瘤中CD4+细胞占12.1%，血液指标无异常。这种 FPEI 和 FCP 复合递送系统展示了向深部肿瘤组织递送 mRNA 的强效靶向性。

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来源期刊

Biomacromolecules 化学-高分子科学

CiteScore

10.60

自引率

4.80%

发文量

417

审稿时长

1.6 months

期刊介绍： Biomacromolecules is a leading forum for the dissemination of cutting-edge research at the interface of polymer science and biology. Submissions to Biomacromolecules should contain strong elements of innovation in terms of macromolecular design, synthesis and characterization, or in the application of polymer materials to biology and medicine. Topics covered by Biomacromolecules include, but are not exclusively limited to: sustainable polymers, polymers based on natural and renewable resources, degradable polymers, polymer conjugates, polymeric drugs, polymers in biocatalysis, biomacromolecular assembly, biomimetic polymers, polymer-biomineral hybrids, biomimetic-polymer processing, polymer recycling, bioactive polymer surfaces, original polymer design for biomedical applications such as immunotherapy, drug delivery, gene delivery, antimicrobial applications, diagnostic imaging and biosensing, polymers in tissue engineering and regenerative medicine, polymeric scaffolds and hydrogels for cell culture and delivery.