Detouring Self-Assembled 3-Methoxy-pyrrole-Based Nanoparticles into Mitochondria to Induce Apoptosis in Lung Cancer Cells

Lung cancer remains a lethal disease globally. Recently, the development and progression of lung cancer were strongly linked with mitochondrial dysfunction. Hence, targeting mitochondria in lung cancer can be an interesting alternative strategy for therapeutic applications. To address this, we have designed and synthesized a 3-methoxy-pyrrole-enamine-triphenylphosphonium cation-based library through a concise chemical strategy. Upon screening this library in cervical (HeLa), colon (HCT-116), breast (MCF7), and lung (A549) cancer cells, we identified a small molecule that self-assembled into nanoscale spherical particles with a positive surface charge. This nanoparticle was confined to the mitochondria to induce mitochondrial damage and produced reactive superoxide in A549 cells. This small molecule self-assembled nanoparticle-mediated mitochondrial damage triggered apoptosis leading to the remarkable killing of A549 cells. These 3-methoxy-pyrrole-enamine-triphenylphosphonium nanoparticles can be used as a tool to understand the chemical biology of mitochondria in lung cancer for chemotherapeutic applications.