1. Curcumin analogue AC17-loaded dissolvable microneedles activate FOXO3 and enhance localized drug delivery for oral squamous cell carcinoma treatment.
- Author
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Ma T, Wang X, Wang Y, Hao Y, Yang X, Yan X, Huang Q, Li Z, Cong B, and Li D
- Subjects
- Humans, Animals, Cell Line, Tumor, Cell Proliferation drug effects, Antineoplastic Agents administration & dosage, Antineoplastic Agents pharmacology, Antineoplastic Agents pharmacokinetics, Antineoplastic Agents chemistry, Apoptosis drug effects, Mice, Inbred BALB C, Mice, Mice, Nude, Male, Curcumin administration & dosage, Curcumin pharmacology, Curcumin pharmacokinetics, Curcumin chemistry, Mouth Neoplasms drug therapy, Forkhead Box Protein O3 metabolism, Drug Delivery Systems, Needles, Carcinoma, Squamous Cell drug therapy
- Abstract
Curcumin, a polyphenol extracted from turmeric, is a potential alternative for the treatment of oral squamous cell carcinoma (OSCC) due to its remarkable anticancer activity and low systemic toxicity. To further enhance the anticancer activity and bioavailability of curcumin, we synthesized a curcumin analogue, AC17, by modifying the benzene ring and methylene group of curcumin. A soluble hyaluronic acid microneedle patch (AC17@HAMN) was developed to ensure accurate and safe delivery of AC17 to tumor tissues. The inhibitory effect of AC17 on OSCC cells was stronger than that of curcumin and some common analogues. Transcriptome sequencing showed that the target genes of AC17 were mainly concentrated in apoptosis, cell cycle and cell senescence pathways. Among them, AC17 induces cell cycle arrest and inhibits cell proliferation mainly by activating FOXO3 signaling. With good penetration and dissolution properties, microneedles can deliver AC17 directly to the tumor site and show good anti-tumor effect. Moreover, AC17@HAMN showed good biosafety. In summary, AC17@HAMN offers high efficiency, minimal invasiveness, and few adverse reactions. This microneedle patch holds great promise for potential clinical applications, especially for the treatment of OSCC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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