title: Targeted Mesoporous Iron Oxide Nanoparticles-Encapsulated Perfluorohexane and a Hydrophobic Drug for Deep Tumor Penetration and Therapy.
abstract: A magneto-responsive energy/drug carrier that enhances deep tumor penetration with a porous nano-composite is constructed by using a tumor-targeted lactoferrin (Lf) bio-gate as a cap on mesoporous iron oxide nanoparticles (MIONs). With a large payload of a gas-generated molecule, perfluorohexane (PFH), and a hydrophobic anti-cancer drug, paclitaxel (PTX), Lf-MIONs can simultaneously perform bursting gas generation and on-demand drug release upon high-frequency magnetic field (MF) exposure. Biocompatible PFH was chosen and encapsulated in MIONs due to its favorable phase transition temperature (56 °C) and its hydrophobicity. After a short-duration MF treatment induces heat generation, the local pressure increase via the gasifying of the PFH embedded in MION can substantially rupture the three-dimensional tumor spheroids in vitro as well as enhance drug and carrier penetration. As the MF treatment duration increases, Lf-MIONs entering the tumor spheroids provide an intense heat and burst-like drug release, leading to superior drug delivery and deep tumor thermo-chemo-therapy. With their high efficiency for targeting tumors, Lf-MIONs/PTX-PFH suppressed subcutaneous tumors in 16 days after a single MF exposure. This work presents the first study of using MF-induced PFH gasification as a deep tumor-penetrating agent for drug delivery.
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu, Taiwan 30013.
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Su
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu, Taiwan 30013.
authors.forename: Jen-Hung
authors.initials: JH
authors.lastname: Fang
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu, Taiwan 30013.
authors.forename: Chia-Ying
authors.initials: CY
authors.lastname: Liao
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu, Taiwan 30013.
authors.forename: Chein-Ting
authors.initials: CT
authors.lastname: Lin
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu, Taiwan 30013.
authors.forename: Yun-Ting
authors.initials: YT
authors.lastname: Li
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu, Taiwan 30013.
authors.forename: Shang-Hsiu
authors.initials: SH
authors.lastname: Hu
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005290:Ferric Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005466:Fluorocarbons / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008280:Magnetics; D053758:Nanoparticles / Q000008:administration & dosage*; D009369:Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics; D013696:Temperature
chemical_list: D000970:Antineoplastic Agents; D005290:Ferric Compounds; D005466:Fluorocarbons; C000499:ferric oxide; C078626:perflexane; D017239:Paclitaxel
keywords: 3D tumor model.; Mesoporous particles; combinatorial therapy; drug delivery; magneto-responsive