title: Doxorubicin and resveratrol co-delivery nanoparticle to overcome doxorubicin resistance.
abstract: With the extensive application of doxorubicin (DOX), DOX resistance has become one of the main obstacles to the effective treatment of breast cancer. In this paper, DOX and resveratrol (RES) were co-encapsulated in a modified PLGA nanoparticle (NPS) to overcome the DOX resistance. CLSM results indicated that DOX and RES were simultaneously delivered into the nucleus of DOX-resistant human breast cancer cells by DOX/RES-loaded NPS. Consequently, DOX/RES-loaded NPS showed significant cytotoxicity on MDA-MB-231/ADR cells and MCF-7/ADR cells. Furthermore, DOX/RES-loaded NPS could overcome DOX resistance by inhibiting the expression of drug resistance-related protein such as P-gp, MRP-1 and BCRP, and induce apoptosis through down-regulating the expression of NF-κB and BCL-2. In tumor-bearing mice, DOX/RES-loaded NPS mainly delivered DOX and RES to tumor tissue. Compared with free DOX, DOX/RES-loaded NPS significantly inhibited the DOX-resistant tumor growth in tumor-bearing mice without causing significant systemic toxicity. In a word, DOX/RES-loaded NPS could overcome the DOX resistance and had the potential in the treatment of DOX-resistant breast cancer.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Meng-Lei
authors.initials: ML
authors.lastname: Huan
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Key laboratory of gastrointestinal pharmacology of Chinese medicine, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Han
authors.initials: H
authors.lastname: Cui
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Dao-Zhou
authors.initials: DZ
authors.lastname: Liu
authors.affiliation: Key laboratory of gastrointestinal pharmacology of Chinese medicine, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Qi-Bing
authors.initials: QB
authors.lastname: Mei
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.|Key laboratory of gastrointestinal pharmacology of Chinese medicine, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Si-Yuan
authors.initials: SY
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage*; D004337:Drug Carriers; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage*
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D013267:Stilbenes; D004317:Doxorubicin; D000077185:Resveratrol