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Folic Acid-Functionalized β-Cyclodextrin for Delivery of Organelle-Targeted Peptide Chemotherapeutics in Cancer.
- Source :
-
Molecular pharmaceutics [Mol Pharm] 2024 Sep 02; Vol. 21 (9), pp. 4498-4509. Date of Electronic Publication: 2024 Jul 28. - Publication Year :
- 2024
-
Abstract
- Recent emphasis on the design of drug delivery systems typically involves the effective transport of a pharmaceutical substance to the disease site with the desired therapeutic efficacy and minimal cytotoxicity. Organelle-targeted peptides have become an integral part of designing an important class of prodrug/prodrug assemblies for new supramolecular therapeutics owing to their favorable biocompatibility, synthetic ease, tunability of their aggregation behavior, and desired functionalization for site-specificity. However, it is still limited due to the low selectivity. We designed a folic acid-functionalized β-cyclodextrin (FA-CD) as a delivery platform for specific and selective delivery of organelle-targeted (such as microtubule, lysosome, and mitochondria) peptide chemotherapeutics to the folate receptor (FR) overexpressing cancer cell lines. Low toxicity was found for the FA-CD and organelle-targeted peptide inclusion complex in FR-negative normal cells, but superior inhibition of tumor growth with no in vivo toxicity was found for the inclusion complex in the xenograft tumor model.
- Subjects :
- Humans
Animals
Mice
Cell Line, Tumor
Organelles drug effects
Organelles metabolism
Antineoplastic Agents pharmacology
Antineoplastic Agents chemistry
Antineoplastic Agents administration & dosage
Mice, Nude
Neoplasms drug therapy
Neoplasms pathology
Neoplasms metabolism
Folate Receptors, GPI-Anchored metabolism
Prodrugs chemistry
Prodrugs pharmacology
Prodrugs administration & dosage
Mitochondria drug effects
Mitochondria metabolism
Female
Folic Acid chemistry
beta-Cyclodextrins chemistry
Drug Delivery Systems methods
Peptides chemistry
Peptides pharmacology
Xenograft Model Antitumor Assays
Subjects
Details
- Language :
- English
- ISSN :
- 1543-8392
- Volume :
- 21
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Molecular pharmaceutics
- Publication Type :
- Academic Journal
- Accession number :
- 39069731
- Full Text :
- https://doi.org/10.1021/acs.molpharmaceut.4c00400