Mitochondria-targeting nanostructures from enzymatically degradable fluorescent amphiphilic polyesters
Subhendu Biswas1, Priya Rajdev1, Ankita Banerjee1
1School of Applied and Interdisciplinary Sciences, Indian Association for the Cultivation of Science (IACS), 2A and 2B Raja. S. C. Mullick Road, Jadavpur, Kolkata 700032, India. psuad2@iacs.res.in.
Nanoscale
|January 28, 2025
Summary
Researchers developed biodegradable fluorescent polyesters for biomedical imaging. Cationic polymers showed rapid uptake and targeted cancer cell mitochondria, while a pH-triggered polymer offered cell-selective targeting, paving the way for advanced drug delivery systems.
Area of Science:
- Polymer Chemistry
- Biomedical Engineering
- Materials Science
Background:
- Water-soluble fluorescent bioprobes are crucial in biomedical research but often non-biodegradable.
- Developing biodegradable alternatives with controlled targeting is essential for advanced applications.
Purpose of the Study:
- To synthesize and characterize novel biodegradable, amphiphilic fluorescent polyesters.
- To investigate the cellular uptake, biodistribution, and targeting capabilities of these polymers in cancer cells.
- To explore their potential as mitochondria-targeted drug delivery systems.
Main Methods:
- Synthesis of naphthalene monoimide (NMI)-functionalized polyesters (P1, P2, P3) via transesterification.
- Characterization of polymer properties, including charge and self-assembly in aqueous media.
- Evaluation of cellular uptake, endosomal escape, and mitochondria targeting in HeLa and NKE cells.
- Assessment of pH-dependent behavior for neutral P3.
Main Results:
- Polymers P1, P2, and P3 self-assembled into fluorescent nanoassemblies with varying cationic properties.
- Cationic polymers (P1, P2) exhibited rapid cellular uptake and efficient mitochondria targeting in HeLa cells.
- Neutral polymer P3 demonstrated pH-triggered cationic behavior and selective mitochondria targeting in cancer cells over non-cancerous cells.
- All polymers showed high cellular uptake (>85%) within 1 hour.
Conclusions:
- Biodegradable NMI-functionalized polyesters offer tunable properties for biomedical applications.
- Cationic and pH-responsive polymers show promise for targeted delivery to cancer cell mitochondria.
- These findings support the development of next-generation, cell-specific drug delivery systems.
