Researchers in the Samit Guha Group at Jadavpur University, Kolkata, India, published in Bioconjugate Chemistry, report a groundbreaking approach to cancer imaging using a dual-targeted, near-infrared, NIR, fluorescent mechanically interlocked molecules, MIMs-peptide, bioconjugate. This innovative system integrates advanced photophysics with dual-targeting capabilities for cancer cell and mitochondrial imaging using super-resolution stimulated emission depletion, STED, microscopy.

The bioconjugate, named (RGDS)₂-Mito-MIMs-TPP⁺, is designed to overcome limitations of conventional NIR dyes, such as poor photostability and aggregation in aqueous environments. The system employs a dual-targeting mechanism, using αVβ3 integrin-binding RGDS peptides to target cancer cells and lipophilic TPP⁺ groups to selectively accumulate in hypernegative mitochondria.

Key Performance Features

• Exceptional photostability and thermal stability

• Ultrabright and narrow-band NIR fluorescence

• Resistance to photobleaching and nucleophilic attack

• Biocompatibility and noncytotoxicity

Using STED microscopy, the bioconjugate enables high-resolution imaging of mitochondrial ultrastructure, including cristae, with spatial resolution down to 45 nm. Time-lapse imaging also allows real-time tracking of mitochondrial dynamics in living carcinoma cells.

The (RGDS)₂-Mito-MIMs-TPP⁺ system represents a significant advance in STED microscopy, offering precise, targeted imaging of cancer cell submitochondrial structures. This research opens avenues for further applications in cellular biology, including studies of mitophagy and organelle cross-talk.