title: Triple Hit with Drug Carriers: pH- and Temperature-Responsive Theranostics for Multimodal Chemo- and Photothermal Therapy and Diagnostic Applications.
abstract: Currently there is a strong need for new drug delivery systems, which enable targeted and controlled function in delivering drugs while satisfying highly sensitive imaging modality for early detection of the disease symptoms and damaged sites. To meet these criteria we develop a system that integrates therapeutic and diagnostic capabilities (theranostics). Importantly, therapeutic efficacy of the system is enhanced by exploiting synergies between nanoparticles, drug, and hyperthermia. At the core of our innovation is near-infrared (NIR) responsive gold nanorods (Au) coated with drug reservoirs--mesoporous silica shell (mSi)--that is capped with thermoresponsive polymer. Such design of theranostics allows the detection of the system using computed tomography (CT), while finely controlled release of the drug is achieved by external trigger, NIR light irradiation--ON/OFF switch. Doxorubicin (DOX) was loaded into mSi formed on the gold core (Au@mSi-DOX). Pores were then capped with the temperature-sensitive poly(N-isopropylacrylamide)-based N-butyl imidazolium copolymer (poly(NIPAAm-co-BVIm)) resulting in a hybrid system-Au@mSi-DOX@P. A 5 min exposure to NIR induces polymer transition, which triggers the drug release (pores opening), increases local temperature above 43 °C (hyperthermia), and upregulates particle uptake (polymer becomes hydrophilic). The DOX release is also triggered by drop in pH enabling localized drug release when particles are taken up by cancer cells. Importantly, the synergies between chemo- and photothermal therapy for DOX-loaded theranostics were confirmed. Furthermore, higher X-ray attenuation value of the theranostics was confirmed via X-ray CT test indicating that the nanoparticles act as contrast agent and can be detected by CT.
authors.affiliation: Faculty of Pharmacy, University of Sydney , NSW 2006, Australia.
authors.forename: Seonmi
authors.initials: S
authors.lastname: Baek
authors.affiliation: Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University , Cheonan 330-714, Republic of Korea.
authors.forename: Rajendra K
authors.initials: RK
authors.lastname: Singh
authors.affiliation: Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University , Cheonan 330-714, Republic of Korea.
authors.forename: Tae-Hyun
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University , Cheonan 330-714, Republic of Korea.
authors.forename: Jae-won
authors.initials: JW
authors.lastname: Seo
authors.affiliation: Department of Biomaterials Science, College of Dentistry, Dankook University , Cheonan 330-714, Republic of Korea.
authors.forename: Ueon Sang
authors.initials: US
authors.lastname: Shin
authors.affiliation: Faculty of Pharmacy, University of Sydney , NSW 2006, Australia.|Charles Perkins Centre, The University of Sydney , NSW 2006, Australia.|Australian Institute of Nanoscale Science and Technology, The University of Sydney , NSW 2006, Australia.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Chrzanowski
authors.affiliation: Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University , Cheonan 330-714, Republic of Korea.
authors.forename: Hae-Won
authors.initials: HW
authors.lastname: Kim
mesh_terms: D003287:Contrast Media / Q000737:chemistry / Q000627:therapeutic use; D016503:Drug Delivery Systems; D065546:Drug Liberation; D006046:Gold / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007259:Infrared Rays; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D043942:Nanotubes / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D012822:Silicon Dioxide / Q000737:chemistry; D013696:Temperature; D000068936:Theranostic Nanomedicine / Q000379:methods*; D014055:Tomography, Emission-Computed
chemical_list: D003287:Contrast Media; D011108:Polymers; D006046:Gold; D012822:Silicon Dioxide
keywords: CT-scannable; biocompatible materials; controlled drug delivery; drug carriers; gold nanorods; mesoporous silica; theranostics; thermoresponsive polymer