title: The Role of Micelle Size in Tumor Accumulation, Penetration, and Treatment.
abstract: The specific sizes that determine optimal nanoparticle tumor accumulation, penetration, and treatment remain inconclusive because many studies compared nanoparticles with multiple physicochemical variables (e.g., chemical structures, shapes, and other physical properties) in addition to the size. In this study, we synthesized amphiphilic block copolymers of 7-ethyl-10-hydroxylcamptothecin (SN38) prodrug and fabricated micelles with sizes ranging from 20 to 300 nm from a single copolymer. The as-prepared micelles had exactly the same chemical structures and similar physical properties except for size, which provided an ideal platform for a systematic investigation of the size effects in cancer drug delivery. We found that the micelle's blood circulation time and tumor accumulation increased with the increase in their diameters, with optimal diameter range of 100 to 160 nm. However, the much higher tumor accumulation of the large micelles (100 nm) did not result in significantly improved therapeutic efficacy, because the large micelles had poorer tumor penetration than the small ones (30 nm). An optimal size that balances drug accumulation and penetration in tumors is critical for improving the therapeutic efficacy of nanoparticulate drugs.
authors.affiliation: †State Key Laboratory of Chemical Engineering and Center for Bionanoengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.
authors.forename: Jinqiang
authors.initials: J
authors.lastname: Wang
authors.affiliation: †State Key Laboratory of Chemical Engineering and Center for Bionanoengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Mao
authors.affiliation: §Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States.
authors.forename: Lye Lin
authors.initials: LL
authors.lastname: Lock
authors.affiliation: †State Key Laboratory of Chemical Engineering and Center for Bionanoengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.
authors.forename: Jianbin
authors.initials: J
authors.lastname: Tang
authors.affiliation: †State Key Laboratory of Chemical Engineering and Center for Bionanoengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.
authors.forename: Meihua
authors.initials: M
authors.lastname: Sui
authors.affiliation: ‡Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.
authors.forename: Weilin
authors.initials: W
authors.lastname: Sun
authors.affiliation: §Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States.
authors.forename: Honggang
authors.initials: H
authors.lastname: Cui
authors.affiliation: ⊥The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310027, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Xu
authors.affiliation: †State Key Laboratory of Chemical Engineering and Center for Bionanoengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.
authors.forename: Youqing
authors.initials: Y
authors.lastname: Shen
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D008823:Micelles
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008823:Micelles; D000077146:Irinotecan; D002166:Camptothecin
keywords: 7-ethyl-10-hydroxylcamptothecin; cancer drug delivery; polymeric micelle; size effect; tumor penetration