title: Resveratrol-loaded folic acid-grafted dextran stearate submicron particles exhibits enhanced antitumor efficacy in non-small cell lung cancers.
abstract: In this study, we have aimed to prepare folic acid-conjugated dextran stearate (DF) polymeric micelles to target resveratrol in lung cancers. The polymeric micelle was nanosized and exhibited a controlled drug release pattern. The resveratrol (RSV)-loaded dextran stearate (RSV-DF) micelles exhibited an enhanced cellular uptake in A549 cells due to the folic acid-based receptor interactions. We have demonstrated that RSV-DF polymeric micelles retain the cytotoxic and metabolic effects of RSV on A549 cancer cells with potencies similar to that of the free compound. Furthermore, RSV-DF showed an enhanced cellular apoptosis of cancer cells compared to that of free RSV. We have found that apoptosis induced by RSV-DF was associated with the higher expression of p53, caspase-3, and BAX than the free RSV. The higher level of BAX and caspase-3 further indicates the involvement of mitochondria-dependent apoptosis in the anticancer efficacy of formulations. Based on these results, it can be concluded that natural compound like RSV could be an interesting prospect to treat lung cancers and the fact that folic acid-conjugated dextran stearate could be a potential carrier to deliver the drug in the cancer cells.
authors.affiliation: Department of Thoracic Surgery, Linyi People's Hospital, Linyi 276003, China.
authors.forename: Qing-Sheng
authors.initials: QS
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics and Gynecology, Linyi People's Hospital, Linyi 276003, China.
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Hu
authors.affiliation: Department of Thoracic Surgery, Linyi People's Hospital, Linyi 276003, China.
authors.forename: Zhi-Dong
authors.initials: ZD
authors.lastname: Wang
authors.affiliation: Department of Oncology, Shandong Provincial Hospital affiliated to Shandong University, Jinan 250021, China.
authors.forename: Zhao-Pei
authors.initials: ZP
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Lanling People's Hospital, Lanling 277700, China.
authors.forename: Ai-Wen
authors.initials: AW
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, The Second Hospital of Jilin University, Changchun 130041, China. Electronic address: jingliu1979@hotmail.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000737:chemistry / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D003911:Dextrans / Q000737:chemistry*; D065546:Drug Liberation; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010316:Particle Size; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry* / Q000633:toxicity; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D003911:Dextrans; D013267:Stilbenes; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D005492:Folic Acid; D053148:Caspase 3; D000077185:Resveratrol
keywords: Anticancer efficacy; Lung cancers; Polymeric micelles; Resveratrol