Lysosomal targeting strategies for design and delivery of bioactive for therapeutic interventions

Abstract

Lysosomes are of particular interest for the design and delivery of pH-dependent pro-drugs, enhancing selectivity and developing strategies to inhibit drug degradation inside the cells. There is great potential to bring intracellular drug delivery and distribution using nanotherapeutic approaches to target lysosomes for therapeutic interventions. Lysosomal targeting strategies involve two contrasting facets. One aspect is to directly target therapeutics to the lysosome through receptor-mediated endocytosis and the other facet involves strategies, which ensure escape from the lysosome in order to prevent their degradation, so that therapeutics may remain intact and available in the cytosol for their further action. It provides a unique opportunity to explore novel treatment strategies and design future drugs for the effective treatment of lysosome-related diseases especially lysosomal storage disorders (LSD), cancer, inflammatory, neurodegenerative conditions (Parkinson's, Alzheimer's and Huntington's diseases) and autoimmune diseases. In this review, we illustrate the fundamentals of membrane trafficking, subcellular organisation, strategies to target lysosomes and its implications for the advance design of efficient drug delivery vectors for safe and effective therapies.

Keywords:

• Lysosomal targeting
• lysosomal escape
• autophagy
• drug design
• localised drug delivery

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The authors are thankful to Department of Science and Technology (DST), New Delhi, India, for providing financial support in the form of a major research grant (YSS/2014/000053). AS and KV acknowledge DST for fellowship.