title: Combined cancer therapy with hyaluronan-decorated fullerene-silica multifunctional nanoparticles to target cancer stem-like cells.
abstract: Cancer stem-like cells (CSCs) are resistant to chemotherapy and highly tumorigenic, which contributes to tumor occurrence and post-treatment relapse. We developed a novel C60 fullerene-silica nanoparticle system surface-decorated with hyaluronan (HA) to target the variant CD44 overexpressed on breast CSCs. Furthermore, doxorubicin hydrochloride (DOX) and indocyanine green (ICG) can be encapsulated in the nanoparticles with ultrahigh encapsulation efficiency (>90%) and loading content (e.g., 48.5% at a drug-to-nanoparticle feeding ratio of 1:1, compared to the commonly used drug-to-nanoparticle feeding ratio of 1:20 with a drug loading content of less than 5%). As a result, the DOX and ICG-laden nanoparticles can be used as a single nanoplatform to achieve combined chemo, photodynamic, and photothermal therapy under near infrared laser irradiation for effective destruction of the breast CSCs both in vitro and in vivo, with no evident systemic toxicity. Moreover, we found the nanoparticles with a higher drug loading content (e.g., 48.5 versus 4.6%) also have significantly higher antitumor efficacy, given the same total drug dose. These results demonstrate the great potential of the multifunctional hybrid nanoparticle system for augmenting cancer therapy by eliminating the CSCs.
authors.affiliation: Department of Biomedical Engineering, The Ohio State University, Columbus, OH 43210, USA; Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Biomedical Engineering, The Ohio State University, Columbus, OH 43210, USA; Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Pranay
authors.initials: P
authors.lastname: Agarwal
authors.affiliation: Department of Biomedical Engineering, The Ohio State University, Columbus, OH 43210, USA; Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Shuting
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA; Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Xiongbin
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Biomedical Engineering, The Ohio State University, Columbus, OH 43210, USA; Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA. Electronic address: he.429@osu.edu.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: He
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D002470:Cell Survival; D065546:Drug Liberation; D005260:Female; D037741:Fullerenes / Q000737:chemistry*; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D006979:Hyperthermia, Induced; D007259:Infrared Rays; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D014411:Neoplastic Stem Cells / Q000473:pathology*; D010778:Photochemotherapy; D010789:Phototherapy; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D037741:Fullerenes; D012822:Silicon Dioxide; D006820:Hyaluronic Acid; C069837:fullerene C60
keywords: CD44; CSC; Chemotherapy; Combination therapy; Photodynamic therapy; Photothermal therapy