PMID- 30102527 OWN - NLM STAT- MEDLINE DCOM- 20180914 LR - 20211204 IS - 1520-5118 (Electronic) IS - 0021-8561 (Linking) VI - 66 IP - 35 DP - 2018 Sep 5 TI - Biotin-Modified Polylactic- co-Glycolic Acid Nanoparticles with Improved Antiproliferative Activity of 15,16-Dihydrotanshinone I in Human Cervical Cancer Cells. PG - 9219-9230 LID - 10.1021/acs.jafc.8b02698 [doi] AB - 15,16-Dihydrotanshinone I (DI), a natural compound isolated from a traditional Asian functional food Salvia Miltiorrhiza Bunge, is known for its anticancer activity. However, poor solubility of DI limits its desirable anticancer application. Herein, polylactic- co-glycolic acid (PLGA) was functionalized with polyethylene glycol (PEG) and biotin to form copolymers PEG-PLGA (PPA) and biotin-PEG-PLGA (BPA). DI was encapsulated in copolymers PPA and BPA to obtain DI-PPA-NPs (NPs = nanoparticles) and DI-BPA-NPs, respectively. The particle size and its distribution, encapsulation efficiency, and in vitro releasing capacity of DI-BPA-NPs were characterized by biophysical methods. MTT assay was used to evaluate the antiproliferative activity of free DI, DI-PPA-NPs, and DI-BPA-NPs in human cervical cancer Hela cells. DI-BPA-NPs showed the highest cytotoxicity on Hela cells with an IC(50) value of 4.55 +/- 0.631 muM, while it was 8.20 +/- 0.849 and 6.14 +/- 0.312 muM for DI and DI-PPA-NPs in 72 h, respectively. The superior antiproliferative activity was supported by the fact that DI-BPA-NPs could be preferentially internalized by Hela cells, owing to their specific interaction between biotin and overexpressed biotin receptors. In addition, DI-BPA-NPs effectively inhibited Hela cell proliferation by inducing G2/M phase cycle arrest and decreasing the intracellular reactive oxygen species (ROS) level by 31.50 +/- 2.29% in 5 min. In summary, DI-BPA-NPs shows improved antiproliferative activity against human cervical cancer as comparing with free DI, demonstrating its application potential in cancer therapy. FAU - Luo, Jingjing AU - Luo J AD - School of Food Science and Engineering , South China University of Technology , Guangzhou 510640 , China. AD - Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety , Guangzhou 510640 , China. FAU - Meng, Xiaofeng AU - Meng X AD - School of Food Science and Engineering , South China University of Technology , Guangzhou 510640 , China. AD - Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety , Guangzhou 510640 , China. FAU - Su, Jianyu AU - Su J AUID- ORCID: 0000-0002-1662-0461 AD - School of Food Science and Engineering , South China University of Technology , Guangzhou 510640 , China. AD - Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety , Guangzhou 510640 , China. AD - Overseas Expertise Introduction Center for Discipline Innovation of Food Nutrition and Human Health (111 Center) , Guangzhou 510640 , China. FAU - Ma, Hang AU - Ma H AUID- ORCID: 0000-0001-7565-6889 AD - Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy , University of Rhode Island , Kingston , Rhode Island 02881 , United States. FAU - Wang, Wen AU - Wang W AD - School of Food Science and Engineering , South China University of Technology , Guangzhou 510640 , China. AD - Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety , Guangzhou 510640 , China. FAU - Fang, Liming AU - Fang L AD - Department of Materials Science and Engineering , South China University of Technology , Guangzhou 510640 , China. FAU - Zheng, Huade AU - Zheng H AD - Department of Materials Science and Engineering , South China University of Technology , Guangzhou 510640 , China. FAU - Qin, Yexia AU - Qin Y AD - Institute of Industrial Technology Research , South China University of Technology , Guangzhou 510640 , China. FAU - Chen, Tianfeng AU - Chen T AUID- ORCID: 0000-0001-6953-1342 AD - Department of Chemistry , Jinan University , Guangzhou , 510632 , China. LA - eng PT - Journal Article DEP - 20180822 PL - United States TA - J Agric Food Chem JT - Journal of agricultural and food chemistry JID - 0374755 RN - 0 (Antineoplastic Agents) RN - 0 (Drug Carriers) RN - 0 (Drugs, Chinese Herbal) RN - 0 (Furans) RN - 0 (Glycolates) RN - 0 (Phenanthrenes) RN - 0 (Polyesters) RN - 0 (Quinones) RN - 0 (Reactive Oxygen Species) RN - 0WT12SX38S (glycolic acid) RN - 459TN2L5F5 (poly(lactide)) RN - 562G9360V6 (dihydrotanshinone I) RN - 6SO6U10H04 (Biotin) SB - IM MH - Antineoplastic Agents/*chemistry/*pharmacology MH - Biotin/chemistry MH - Cell Cycle/drug effects MH - Cell Proliferation/drug effects MH - Drug Carriers/chemical synthesis/chemistry MH - Drug Compounding MH - Drug Delivery Systems MH - Drugs, Chinese Herbal/*chemistry/*pharmacology MH - Female MH - Furans MH - Glycolates/chemistry MH - HeLa Cells MH - Humans MH - Particle Size MH - Phenanthrenes/*chemistry/*pharmacology MH - Polyesters/chemistry MH - Quinones MH - Reactive Oxygen Species/metabolism MH - Salvia miltiorrhiza/*chemistry MH - Uterine Cervical Neoplasms/*drug therapy/metabolism/physiopathology OTO - NOTNLM OT - 15,16-dihydrotanshinone I OT - PLGA nanoparticles OT - antiproliferative OT - biotin OT - cervical cancer OT - targeted delivery EDAT- 2018/08/14 06:00 MHDA- 2018/09/15 06:00 CRDT- 2018/08/14 06:00 PHST- 2018/08/14 06:00 [pubmed] PHST- 2018/09/15 06:00 [medline] PHST- 2018/08/14 06:00 [entrez] AID - 10.1021/acs.jafc.8b02698 [doi] PST - ppublish SO - J Agric Food Chem. 2018 Sep 5;66(35):9219-9230. doi: 10.1021/acs.jafc.8b02698. Epub 2018 Aug 22.