脂质体凭借其生物相容性和作为载体的多功能性，在药物输送领域中扮演着重要角色。通过在表面装饰親水性聚乙二醇（PEG）分子，得到的隐形脂质体在脂质体技术方面代表了一个重要转折点，与裸露脂质体相比，在药物代谢动力学特征方面取得了显著改进。然而，有效靶向脂质体的产生，即癌症治疗的核心问题，面临着多个困难和临床阶段的失败。主动靶向仍然是脂质体所面临的挑战。在这方面，我们设计了一种新型的超隐形免疫脂质体(SSIL2)，由稳定聚合物覆蓋脂质体的PEG-两亲性磷脂衍生物组成。此外，其对应物质，连接到曲妥珠单抗(Trastuzumab)的抗原结合片段(Fab'TRZ-PEG-两亲性磷脂)，牢固地锚定在脂质体表面，并正确定向靶向部分向外。通过本研究，我们评估并比较了SSIL2在体外细胞系和活体斑马鱼幼仔和啮齿动物模型研究中与经典隐形脂质体和隐形免疫脂质体的性能。总的来说，SSIL2显示出卓越的体外和体内结果，无论是在安全性还是抗癌有效性方面，从而在靶向癌症治疗中迈出了一步，并有助于未来的发展。此文章受版权保护。保留所有权利。

Liposomes play an important role in the field of drug delivery by virtue of their biocompatibility and versatility as carriers. Stealth liposomes, obtained by surface decoration with hydrophilic polyethylene glycol (PEG) molecules, represented an important turning point in liposome technology, leading to significant improvements in the pharmacokinetic profile compared to naked liposomes. Nevertheless, the generation of effective targeted liposomes - a central issue for cancer therapy - has faced several difficulties and clinical phase failures. Active targeting remains a challenge for liposomes. In this direction, we designed a new Super Stealth Immunoliposomes (SSIL2) composed of a PEG-bi-phospholipids derivative that stabilizes the polymer shielding over the liposomes. Furthermore, its counterpart, conjugated to the fragment antigen-binding of trastuzumab (Fab'TRZ -PEG-bi-phospholipids), is firmly anchored on the liposomes surface and correctly orients outward the targeting moiety. Throughout this study, the performances of SSIL2 are evaluated and compared to classic stealth liposomes and stealth immunoliposomes in vitro in a panel of cell lines and in vivo studies in zebrafish larvae and rodent models. Overall, SSIL2 shows superior in vitro and in vivo outcomes, both in terms of safety and anticancer efficacy, thus representing a step forward in targeted cancer therapy, and valuable for future development. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.