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- Title
CD44-specific short peptide A6 boosts cellular uptake and anticancer efficacy of PEGylated liposomal doxorubicin in vitro and in vivo.
- Authors
Yazdian-Robati, Rezvan; Amiri, Ehsan; Kamali, Hossein; Khosravi, Aysun; Taghdisi, Seyed Mohammad; Jaafari, Mahmoud Reza; Mashreghi, Mohammad; Moosavian, Seyedeh Alia
- Abstract
Although liposomes have improved patient safety and the pharmacokinetic profile of free drugs, their therapeutic efficacy has only shown marginal improvement. The incorporation of active-targeted ligands to enhance cellular uptake has shown promise in preclinical studies. However, no active-targeted liposomes have successfully translated into clinical use thus far. This study aimed to evaluate the targeting ability and antitumor efficiency of A6, a specific short peptide (KPSSPPEE) when incorporated into PEGylated liposomal doxorubicin (PLD). The results revealed significantly enhanced cellular uptake. The cytotoxicity of the formulations was determined by 3 h and 6 h incubation of formulations with cells, followed by 48 h incubation to evaluate the targeted ability of the formulations and the results indicated the higher cytotoxicity of A6-PLD (IC50 of 7.52 µg/mL after 6 h incubation) in the CD44 overexpressing C26 cell line compared to non-targeted PLD (IC50 of 15.02 µg/mL after 6 h incubation). However, CD44-negative NIH-3T3 cells exhibited similar uptake and in vitro cytotoxicity for both A6-PLD (IC50 of 38.05 µg/mL) and PLD (IC50 of 34.87 µg/mL). In animal studies, A6-PLD demonstrated significantly higher tumor localization of doxorubicin (Dox) (~ 8 and 15 µg Dox/g tumor for 24 and 48 after injection) compared to PLD (~ 6 and 8 µg Dox/g tumor for 24 and 48 after injection), resulting in effective inhibition of tumor growth. The median survival time (MST) for Dextrose 5% was 10, PLD was 14 and A6-PLD was 22 days. In conclusion, A6-PLD, a simple and effective targeted liposome formulation, exhibits high potential for clinical translation. Its improved targetability and antitumor efficacy make it a promising candidate for future clinical applications.
- Subjects
PEPTIDES; ANTINEOPLASTIC agents; LIPOSOMES; CYTOTOXINS; TUMOR growth; SURVIVAL rate; DOXORUBICIN
- Publication
Cancer Nanotechnology (1868-6958), 2023, Vol 14, Issue 1, p1
- ISSN
1868-6958
- Publication type
Article
- DOI
10.1186/s12645-023-00236-0