Abstract

Hybrid Liposomes of Nanoparticles Achieve Targeted Accumulation and Induce Apoptosis in TE-4 Esophageal Cancer Cells Without Antitumor Drugs

Junna Takai, Masaki Okumura, Koichi Goto, Yoko Matsumoto and Hideki Ichihara*

Nanoparticle Hybrid Liposomes (HL), composed of L-α-dimyristoylphosphatidylcholine (DMPC) vesicles and polyoxyethylene (25) dodecyl ether (C12 (EO)25 ) micelles, were prepared by ultrasonic irradiation in a 5% glucose solution. The HL remained stable for over one month, maintaining a hydrodynamic diameter below 100 nm. HL exhibited significant growth-inhibitory effects on esophageal cancer (TE-4) cells in the absence of antitumor drugs, as determined by the WST-8 assay. Flow cytometric analysis revealed an increase in apoptotic cells following HL treatment. Fluorescent substrate-based assays further demonstrated activation of caspase-3, -8, and -9, indicating that HL induced apoptosis via a caspase-dependent pathway in TE-4 cells. Accumulation of HL containing fluorescent probe (1-palmitoyl-2-[12-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]dodecanoyl]-glycero-3-phosphocholine (NBDPC); HL/NBDPC)) was observed by fluorescence microscopy in vitro. Selective accumulation of HL containing near infrared fluorescent probe (indocyanine green (ICG); HL/ICG) within tumors in liver metastasis mouse models of TE-4 esophageal cancer was demonstrated by in vivo imaging. These results suggest that HL exert a potent growth inhibitory effects on TE-4 cells via apoptosis, selectively accumulate in TE-4 cells both in vitro and in vivo, and hold great promise as a potential cancer therapeutic drug.

Published Date: 2026-01-12; Received Date: 2025-12-12