Journal Article

Precision‐Guided Stealth Missiles in Biomedicine: Biological Carrier‐Mediated Nanomedicine Hitchhiking Strategy

Yang, Qiusheng, Liu, Chao, Wang, Dong, Qiu, Zhiwei, Wan, Dongling, Wu, Wencheng, Xu, Xuefeng, Cui, Hanxiao, Yang, Zhenghui, Zhang, Lizhihong, Li, Wenhao, Tian, Xiaorong, Yang, Zhicheng, Zhang, Deyu, Wang, Xinyue, Du, Wei, Huang, Haojie, Zhou, Yuyan

2025

Overview

Nanodrug delivery systems (NDDS) have demonstrated broad application prospects in disease treatment, prevention, and diagnosis due to several advantages, including functionalization capability, high drug‐loading capacity, drug stability protection, and the enhanced permeability and retention (EPR) effect. However, their clinical translation still faces multiple challenges, including rapid clearance by the reticuloendothelial system (RES), poor targeting specificity, and insufficient efficiency in crossing biological barriers. To address these limitations, researchers have developed the biological carrier‐mediated nanomedicine hitchhiking strategy (BCM‐NHS), which leverages circulating cells, proteins, or bacteria as natural “mobile carriers” to enhance drug delivery. This approach enables nanocarriers to inherit the intrinsic biological properties, endowing them with immune evasion, prolonged circulation, dynamic targeting, biocompatibility, biodegradability, and naturally optimized biological interfaces. Here, a systematic overview of the BCM‐NHS is provided. First, the review delves into the methods of nanoparticles (NPs) binding and immobilization, encompassing both the surface‐attachment‐mediated “backpack” strategy and the encapsulation‐based “Trojan horse” strategy. Second, the classification of biological carriers, including both cell‐based and non‐cell‐based carriers, is elucidated. Third, the physical properties and release mechanisms of these nanomaterials are thoroughly described. Finally, the latest applications of BCM‐NHS in therapeutic and diagnostic contexts across various disease models including tumor, ischemic stroke, and pneumonia are highlighted. Diagram illustrating the binding methods of NPs and biological barriers. The biological carrier‐mediated nanomedicine hitchhiking strategy (BCM‐NHS) utilizes two distinct techniques: the surface‐based “Backpack” method, which relies on ligand‐receptor binding, covalent conjugation, and non‐covalent binding, and the encapsulated “Trojan horse” approach, which employs neutrophils and monocytes/macrophages as natural delivery vehicles. Created with Biorender (Agreement number: GW2854RTK7).

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
• Subject: Animals / biological carrier‐mediated nanomedicine hitchhiking strategy (BCM‐NHS) / Blood / Blood platelets / Blood-brain barrier / Cells / covalent conjugation / Disease / Drug Carriers / Drug delivery systems / Drug Delivery Systems - methods / Efficiency / encapsulation / Hemoglobin / Humans / Leukocytes / Ligands / ligand–receptor interactions / Lymphocytes / Nanomaterials / Nanomedicine - methods / Nanoparticles / Nanoparticles - chemistry / Neutrophils / non‐covalent conjugation / Peptides / Physiology / Precision Medicine - methods / Proteins / Review / Toxicity