Breaking barriers: targeted delivery of resveratrol in lung cancer using folate-integrated and pH-responsive hybrid nanocarriers
Abstract Background Targeting lung cancer while sparing healthy cells is the cornerstone of chemotherapy; however, bioavailability issues and complex biological barriers prevent their accumulation in the tumor sites. Working on this rationale, the present study was aimed to develop novel and afforda...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SpringerOpen
2025-07-01
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| Series: | Future Journal of Pharmaceutical Sciences |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s43094-025-00850-2 |
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| Summary: | Abstract Background Targeting lung cancer while sparing healthy cells is the cornerstone of chemotherapy; however, bioavailability issues and complex biological barriers prevent their accumulation in the tumor sites. Working on this rationale, the present study was aimed to develop novel and affordable hybrid nanocarriers combined with folate and pH-responsive functionalities for targeted delivery of Resveratrol (FOL-RSV-LPHNCs). Methods The developed FOL-RSV-LPHNCs were first optimized by the design of experiment with Box–Behnken design and then characterized for physicochemical properties, cytotoxicity, in vivo pharmacokinetic behavior and anticancer efficacy in the xenograft mouse model. Results Results showed that optimized FOL-RSV-LPHNCs had a monodisperse spherical size of 247.86 ± 0.30 nm, entrapment efficiency of 93.72 ± 0.10% and drug loading of 4.16 ± 0.02%, respectively. The amount of RSV released from FOL-RSV-LPHNCs was 96.53 ± 2.16% at pH 5.8 and 23.21 ± 2.01% at pH 7.4, indicative of a pH-responsive release pattern and good physiological stability. In vitro cytotoxicity study revealed that FOL-RSV-LPHNCs remarkably inhibited the viability of A549 cells and produced negligible toxic effect on Wi-38 healthy cells. The single-dose intravenous administration of FOL-RSV-LPHNCs displayed 3.79-fold longer AUC0-∞, 3.54-fold greater t1/2 and 4.16-fold higher MRT0-∞ than free RSV. Finally, in vivo targeting and anticancer studies demonstrated that FOL-RSV-LPHNCs selectively internalized to the cancerous region and suppressed the tumor volume with an 8.66-fold higher rate in the xenograft mouse model. The folate receptor-mediated uptake mainly facilitates this superior therapeutic response which was further confirmed by in silico molecular docking and dynamic simulation. Conclusions Our findings suggested that FOL-RSV-LPHNCs might serve as an auspicious nanoplatform for targeted drug delivery and treatment of lung cancer. Graphical Abstract |
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| ISSN: | 2314-7253 |