4.6 Article

Lysosome-Targeting Strategy Using Polypeptides and Chimeric Molecules

Journal

ACS OMEGA
Volume 7, Issue 1, Pages 5-16

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsomega.1c04771

Keywords

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Funding

  1. CSIR, New Delhi
  2. KVPY
  3. Prime Minister's Research Fellows (PMRF) Scheme
  4. DST-Nano mission [DST/NM/NB/2018/16]

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This review discusses lysosomes and their impact on diseases, as well as strategies and therapeutic applications of synthesizing peptides/chimeric molecules. It also introduces the use of lysosome-targeting nanocarriers for molecular delivery and the development of chimeric architectures with cell-specific degradation capabilities.
Lysosomes are membranous compartments containing hydrolytic enzymes, where cellular degradation of proteins and enzymes among others occurs in a controlled manner. Lysosomal dysfunction results in various pathological situations, such as several lysosomal storage disorders, neuro-degeneration, infectious diseases, cancers, and aging. In this review, we have discussed different strategies for synthesizing peptides/chimeric molecules, their lysosome-targeting ability, and their ability to treat several lysosomal associated diseases, including lysosomal storage diseases and cancers. We have also discussed the delivery of cargo molecules into the lysosome using lysosometargeting ligand-decorated nanocarriers. The introduction of a protein-binding ligand along with a lysosome-targeting ligand to manufacture a chimeric architecture for cell-specific protein (extracellular and membrane protein) degradation ability has been discussed thoroughly. Finally, the future applications of these lysosome-targeting peptides, nanocarriers, and chimeric molecules have been pointed out.

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