Lysosome-targeting naphthalimide-based AIEE nanoaggregates as a dual inducer of autophagy and apoptosis in cancer therapy.

Authors

Sayantani Mukhopadhyay, Priyam Ghosh, Siddhartha Sankar Ghosh, Parameswar Krishnan Iyer

Published in

Nanoscale. Jul 20, 2026. Epub Jul 20, 2026.

Abstract

Hallmarks of cancer remain incompletely addressed due to the lack of efficient treatments. In translational healthcare, aggregation-induced emission/aggregation-induced enhanced emission luminogens (AIE/AIEEgens), which display strong photoluminescence upon aggregation, have broad applications in therapeutic imaging, selective organelle tracking, and biomolecular detection. Carefully designed AIE/AIEEgens can generate intracellular reactive oxygen species (ROS), thereby activating apoptotic pathways. Here, we report a novel naphthalimide-based fluorophore functionalized with morpholine and 6-hydroxyquinoline units. DFT studies confirmed a donor-acceptor framework, with morpholine as the electron donor and the naphthalimide core as the electron acceptor. The synthesized AIEEgen morpholinonaphthalimide-6-hydroxyquinoline (M6HQ) efficiently targeted lysosomes and exhibited cytotoxicity in IMR-32 and MCF-7 cells. M6HQ enhanced lysosomal activity that instigated increased LC3-II/LC3-I expression and decreased p62 expression, indicating autophagic induction. Additionally, M6HQ elevated intracellular ROS production, leading to mitochondrial depolarization, cell cycle arrest, reduced cell migration, and apoptosis in IMR-32 and MCF-7 cells. Elevated levels of apoptotic marker proteins (cleaved caspase-3 and -9) in treated cells further supported the apoptotic cell death pathway. These findings highlight lysosome-targeted naphthalimide-based AIEE nanoaggregates as multifunctional theranostic agents that induce both autophagy and apoptosis, offering a dual-pathway strategy to overcome drug resistance and improve cancer therapy.

PMID:
42475021
Bibliographic data and abstract were imported from PubMed on 20 Jul 2026.

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