title: Investigating the optimal size of anticancer nanomedicine.
abstract: Nanomedicines (NMs) offer new solutions for cancer diagnosis and therapy. However, extension of progression-free interval and overall survival time achieved by Food and Drug Administration-approved NMs remain modest. To develop next generation NMs to achieve superior anticancer activities, it is crucial to investigate and understand the correlation between the physicochemical properties of NMs (particle size in particular) and their interactions with biological systems to establish criteria for NM optimization. Here, we systematically evaluated the size-dependent biological profiles of three monodisperse drug-silica nanoconjugates (NCs; 20, 50, and 200 nm) through both experiments and mathematical modeling and aimed to identify the optimal size for the most effective anticancer drug delivery. Among the three NCs investigated, the 50-nm NC shows the highest tumor tissue retention integrated over time, which is the collective outcome of deep tumor tissue penetration and efficient cancer cell internalization as well as slow tumor clearance, and thus, the highest efficacy against both primary and metastatic tumors in vivo.
authors.affiliation: Departments of Materials Science and Engineering.
authors.forename: Li
authors.initials: L
authors.lastname: Tang
authors.affiliation: Food Science and Human Nutrition.
authors.forename: Xujuan
authors.initials: X
authors.lastname: Yang
authors.affiliation: Departments of Materials Science and Engineering.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yin
authors.affiliation: Departments of Materials Science and Engineering.
authors.forename: Kaimin
authors.initials: K
authors.lastname: Cai
authors.affiliation: Departments of Materials Science and Engineering.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Departments of Materials Science and Engineering.
authors.forename: Isthier
authors.initials: I
authors.lastname: Chaudhury
authors.affiliation: Departments of Materials Science and Engineering.
authors.forename: Catherine
authors.initials: C
authors.lastname: Yao
authors.affiliation: Department of Pharmaceutical Science, Guangdong Pharmaceutical College, Guangzhou, Guangdong, 510006, China; and.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Departments of Materials Science and Engineering.
authors.forename: Mincheol
authors.initials: M
authors.lastname: Kwon
authors.affiliation: Food Science and Human Nutrition.
authors.forename: James A
authors.initials: JA
authors.lastname: Hartman
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801;
authors.forename: Iwona T
authors.initials: IT
authors.lastname: Dobrucki
authors.affiliation: Bioengineering.
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Dobrucki
authors.affiliation: Department of Population Health and Pathobiology, North Carolina State University, Raleigh, NC 27606.
authors.forename: Luke B
authors.initials: LB
authors.lastname: Borst
authors.affiliation: Pathobiology, and.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Lezmi
authors.affiliation: Food Science and Human Nutrition, jianjunc@illinois.edu t-fan@illinois.edu alf@illinois.edu helferic@illinois.edu.
authors.forename: William G
authors.initials: WG
authors.lastname: Helferich
authors.affiliation: Departments of Materials Science and Engineering, jianjunc@illinois.edu t-fan@illinois.edu alf@illinois.edu helferic@illinois.edu.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Ferguson
authors.affiliation: Veterinary Clinical Medicine, and jianjunc@illinois.edu t-fan@illinois.edu alf@illinois.edu helferic@illinois.edu.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Fan
authors.affiliation: Departments of Materials Science and Engineering, Bioengineering, jianjunc@illinois.edu t-fan@illinois.edu alf@illinois.edu helferic@illinois.edu.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Cheng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000627:therapeutic use; D006801:Humans; D061986:MCF-7 Cells; D008819:Mice, Nude; D058726:Nanoconjugates; D050997:Nanomedicine; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy; D010316:Particle Size; D012822:Silicon Dioxide / Q000737:chemistry; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D058726:Nanoconjugates; D012822:Silicon Dioxide
keywords: drug delivery; mathematical model; nanomedicine; silica nanoparticle; size effect