Phospholipid‐Drug Conjugates Self‐Organized into Well‐Defined Supramolecular Nanotubes for Efficient Drug Delivery

Z Zhiguo Gao (State Key Laboratory of Natural Medicines Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases and Jiangsu Key Laboratory of Drug Design and Optimization Center of Advanced Pharmaceuticals and Biomaterials, School of Life Science and Technology China Pharmaceutical University Nanjing 211198 China) W Wei He K Ke Qin J Jiaqi Xing (State Key Laboratory of Natural Medicines Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases and Jiangsu Key Laboratory of Drug Design and Optimization Center of Advanced Pharmaceuticals and Biomaterials, School of Life Science and Technology China Pharmaceutical University Nanjing 211198 China) Y Yi Liang (Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering) Y Yinan Zhang (Stoddart Institute of Molecular Science, Department of Chemistry, Zhejiang Key Laboratory of Excited-State Energy Conversion and Energy Storage, State Key Laboratory of Silicon and Advanced Semiconductor Materials) B Baiwang Sun (School of Chemistry and Chemical Engineering Southeast University Nanjing 210096 China) R Ran Mo

Abstract

AbstractControlled self‐organization of amphiphilic phospholipid camptothecin (CPT) conjugates (named PCCs) selectively forms supramolecular nanotubes with varying lengths and polydispersity. Our study elucidates the underlying mechanisms governing PCC assembly, demonstrating that π–π stacking interactions derived from the planar, conjugated structure of CPT play a pivotal role in nanotube formation. Precise modulation of the hydrophobic characteristics of PCC linkers enables fine‐tuning of π‐stacking strength, thereby controlling the length of the nanotubes, ranging from the nano‐ to micro‐scale. With exceptionally high drug‐loading efficiencies (43.9% to 52.3%) and stimulus‐responsive release properties, the optimized PCC nanotubes exhibit tumor‐selective cytotoxicity of 20‐ to 50‐fold greater potency against tumor cells compared to normal cells. Furthermore, PCC nanotubes of intermediate length (0.3–0.5 µm) display prolonged circulation times than conventional liposomes, resulting in enhanced tumor‐targeting and therapeutic efficacy.

Article Details

Volume / Issue Vol. 64, Issue 41
Published October 06, 2025
ISSN 1433-7851
Publisher Wiley

Journal Info

Angewandte Chemie International Edition

Wiley

ISSN: 1433-7851 Physical Sciences

Authors (8)

Z

Zhiguo Gao

State Key Laboratory of Natural Medicines Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases and Jiangsu Key Laboratory of Drug Design and Optimization Center of Advanced Pharmaceuticals and Biomaterials, School of Life Science and Technology China Pharmaceutical University Nanjing 211198 China

W

Wei He

K

Ke Qin

J

Jiaqi Xing

State Key Laboratory of Natural Medicines Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases and Jiangsu Key Laboratory of Drug Design and Optimization Center of Advanced Pharmaceuticals and Biomaterials, School of Life Science and Technology China Pharmaceutical University Nanjing 211198 China

Y

Yi Liang

Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering

Y

Yinan Zhang

Stoddart Institute of Molecular Science, Department of Chemistry, Zhejiang Key Laboratory of Excited-State Energy Conversion and Energy Storage, State Key Laboratory of Silicon and Advanced Semiconductor Materials

B

Baiwang Sun

School of Chemistry and Chemical Engineering Southeast University Nanjing 210096 China

R

Ran Mo