Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, (China).
Department of Pharmaceutics, College of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, (China).
Sci Adv. 2024 Oct 25;10(43):eadq2072. doi: 10.1126/sciadv.adq2072. Epub 2024 Oct 23.
Ex vivo or in vivo cell-hitchhiking has emerged as a potential means for efficient drug delivery and various disease therapies. However, many challenges remain, such as the complicated engineering process and dependence on ligand-receptor interaction. Here, we present a simple in vivo platelet-hitchhiking strategy based on self-assembling peptides without ligand modification. The engineered peptide nanofibers can hitchhike ultrafast (<5 s) and efficiently on both resting and activated platelets in a receptor-independent and species-independent manner. Mechanistic studies showed that unique secondary structure of nanofibers, which lead to surface exposure of hydrophobic and hydrogen bond-forming groups, might primarily contribute to the selective and efficient platelet-hitchhiking behavior. After intravenous injection, these peptide nanofibers hitchhiked in situ on circulating platelets and achieved almost 20-fold lung accumulation. Our study provides not only a different paradigm of in vivo platelet-hitchhiking beyond ligand-receptor recognition but also a potential strategy for lung-targeted drug delivery and pulmonary disease therapy.
细胞搭便车（cell-hitchhiking）技术已成为高效药物输送和各种疾病治疗的一种潜在手段，无论是在体（in vivo）还是离体（ex vivo）。然而，该技术仍面临许多挑战，例如复杂的工程化过程和对配体-受体相互作用的依赖。在此，我们提出了一种基于无需配体修饰的自组装肽的简单体内血小板搭便车策略。该工程化的肽纳米纤维能够以受体非依赖性和物种非依赖性的方式，超快（<5 s）且高效地搭乘静止和激活的血小板。机制研究表明，纳米纤维独特的二级结构导致疏水性和亲氢键形成基团的表面暴露，可能主要促成了对血小板的选择性和高效搭乘行为。静脉注射后，这些肽纳米纤维在循环血小板上原位搭乘，并在肺部实现了近 20 倍的积累。我们的研究不仅提供了一种超越配体-受体识别的新型体内血小板搭便车范例，还为肺部靶向药物输送和肺部疾病治疗提供了一种潜在策略。
