Quinoxalinone-based, endoplasmic reticulum-targeting photosensitizer nanoparticles for tumor photodynamic therapy.

Authors

Chao Sun, Lici Wang, Tao Li, Lei Duan, Yan Dong, Ji Li

Published in

Bioengineering & translational medicine. Pages e70170. Aug 09, 2026. Epub Aug 09, 2026.

Abstract

The endoplasmic reticulum (ER) is an indispensable organelle responsible for the synthesis and transport of proteins and membrane lipids, playing a critical role in numerous physiological and pathological processes. Leveraging the properties of the ER, we developed novel quinoxalinone-based, ER-targeting photosensitizer nanoparticles (Qui-PS NPs) by conjugating an ER-specific targeting peptide(RACR) and evaluated their photodynamic therapy (PDT) efficacy. The size, morphology, cellular uptake, ER targeting capability, cell viability, biodistribution, and antitumor efficacy were assessed using dynamic light scattering, transmission electron microscopy, confocal microscopy, CCK-8 assay, ICP-Mass spectrometry, and tumor volume measurements, respectively. The results demonstrated that the synthesized Qui-PS NPs possessed an average diameter of $79.74\pm 9.4$ nm, a polydispersity index (PDI) of $0.23\pm 0.02$ , and a Zeta potential of $-11.63\pm 2.86$ mV. These nanoparticles exhibited near-infrared fluorescence emission centered at 830 nm and demonstrated superior singlet oxygen (¹O₂) generation capability. The NPs were readily internalized by MCF-7 cells, displayed specific ER targeting, and induced cytotoxic effects upon light irradiation, with an $I{C}_{50}$ value of $3.2\pm 0.06$ μg/mL. In tumor-bearing mice, Qui-PS NPs preferentially accumulated in tumor tissue and significantly suppressed tumor progression under light irradiation, with minimal impact on body weight. These findings suggest that these ER-targeted NPs represent a promising nanoplatform for potential application in tumor PDT.

PMID:
42577522
Bibliographic data and abstract were imported from PubMed on 16 Sep 2026.

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