title: Amphiphilic dendritic nanomicelle-mediated co-delivery of 5-fluorouracil and doxorubicin for enhanced therapeutic efficacy.
abstract: Combination cancer therapy has attracted considerable attention due to its enhanced antitumor efficacy and reduced toxicity granted by synergistic effects over monotherapy. The application of nanotechnology is expected to achieve coencapsulation of multiple anticancer agents with enhanced therapeutic efficacy. Herein, a unique nanomicelle based on amphiphilic dendrimer (AmD) consisting of a hydrophilic polyamidoamine dendritic shell and a hydrophobic polylactide core is developed for effectively loading and shuttling 5-fluorouracil (5-Fu) and doxorubicin (Dox). The yielded drug-encapsulated dendritic nanomicelle (5-Fu/Dox-DNM) has a modest average size of 68.6 ± 3.3 nm and shows pH-sensitive drug release manner. The parallel activity of 5-Fu and Dox show synergistic anticancer efficacy. The IC50value of 5-Fu/Dox-DNM toward human breast cancer (MDA-MB-231) cells was 0.25 μg/mL, presenting an 11.2-fold and 6.1-fold increase in cytotoxicity compared to Dox-DNM and 5-Fu-DNM, respectively. Furthermore, 5-Fu/Dox-DNM significantly inhibits the progression of tumor growth in the MDA-MB-231 xenograft tumor mice model. In conclusion, we have demonstrated that our AmD-based combination therapeutic system has promising potential to open an avenue for coencapsulation of multiple chemotherapeutic agents to promote superior anticancer effect.
authors.affiliation: a Department of Pharmacy , The First People's Hospital of Changzhou , Changzhou , China.
authors.forename: Rui
authors.initials: R
authors.lastname: Han
authors.affiliation: b Department of Chemistry and Biochemistry , The Ohio State University , Columbus, OH , USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: c Division of Pharmacology, College of Pharmacy , The Ohio State University , Columbus, OH , USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Kang
authors.affiliation: d Nanjing Haiguang Applied Chemistry Research Institute, Aosaikang Pharmaceutical Co., Ltd , Nanjing , China.
authors.forename: Huijing
authors.initials: H
authors.lastname: Sun
authors.affiliation: e Department of Acupuncture , The First People's Hospital of Changzhou , Changzhou , China.
authors.forename: Wenguang
authors.initials: W
authors.lastname: Wei
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004304:Dosage Forms; D004317:Doxorubicin / Q000737:chemistry* / Q000494:pharmacology*; D016503:Drug Delivery Systems; D005260:Female; D005472:Fluorouracil / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D015394:Molecular Structure; D049329:Nanostructures; D009374:Neoplasms, Experimental / Q000188:drug therapy*
chemical_list: D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D004304:Dosage Forms; D008823:Micelles; D004317:Doxorubicin; D005472:Fluorouracil
keywords: 5-fluorouracil; Amphiphilic dendrimer; anticancer nanomicelle; doxorubicin; drug delivery; synergistic effects