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Differences in the Intracellular Localization of Methylated β-Cyclodextrins-Threaded Polyrotaxanes Lead to Different
Yuma Yamada1,2, Shinnosuke Daikuhara1, Atsushi Tamura3
1Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Biomolecules
|June 28, 2023
Summary
Targeted delivery of methylated β-cyclodextrins-threaded polyrotaxane (Me-PRX) enhances autophagy induction. Specific organelle targeting influences Me-PRX efficacy and cellular response, optimizing therapeutic potential for protein-aggregation diseases.
Area of Science:
- Biochemistry
- Cell Biology
- Nanotechnology
Background:
- Autophagy activation is a therapeutic strategy for diseases involving protein and organelle accumulation.
- Methylated β-cyclodextrins-threaded polyrotaxane (Me-PRX) is a supramolecular polymer that induces autophagy.
- Previous studies showed enhanced autophagy with mitochondria-targeted Me-PRX via MITO-Porter nanocarrier.
Purpose of the Study:
- To quantitatively evaluate the intracellular organelle localization of naked Me-PRX and MITO-Porter (Me-PRX).
- To assess organelle injury and cell viability based on Me-PRX administration route.
- To determine the role of organelle targeting in autophagy induction efficacy.
Main Methods:
- Quantitative evaluation of intracellular organelle localization (mitochondria, endoplasmic reticulum, lysosomes).
- Organelle injury assays.
- Cell viability assays.
Main Results:
- Naked Me-PRX and MITO-Porter (Me-PRX) exhibited distinct intracellular organelle localization patterns.
- Organelle injury and autophagy induction varied depending on the administration route and targeted organelle.
- MITO-Porter (Me-PRX) achieved significant autophagy induction at a lower dosage compared to naked Me-PRX.
Conclusions:
- The specific organelle targeted by Me-PRX influences autophagy induction levels.
- Intracellular localization and subsequent organelle interactions are critical for the efficacy of autophagy-inducing molecules.
- Targeted delivery strategies can optimize Me-PRX for therapeutic applications in autophagy-related diseases.
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