title: Optical imaging and anticancer chemotherapy through carbon dot created hollow mesoporous silica nanoparticles.
abstract: Multifunctional nanocarrier-based theranostics is currently considered to solve some key unmet challenges in cancer treatment. Here we report a nanocarrier platform, named carbon dot (CD) created mesoporous hollow organosilica (C-hMOS) nanoparticles, to deliver anticancer drug and to enable optical imaging. The hollow structure was formed by the removal of a nanorod core template, and at the same time, the fluorescent signal was endowed from the heat-treated organosilica network. Thanks to the hollow and mesoporous structure, the C-hMOS effectively loaded doxorubicin (DOX) for cancer chemotherapy. The DOX was released from C-hMOS highly sustainably (over 12days) and pH-dependently (pH 5.0 >pH 7.4). The DOX-loading C-hMOS internalized cancer cells efficiently (>90%), and induced cellular apoptosis including the expression of caspase-3. The treatment of C-hMOS to cancer cells enabled multi-color visualization in vitro, suggesting the possibility of cell tracing. Moreover, when injected intratumorally in mice, the C-hMOS exhibited strong optical signals in vivo along with a high optical stability (over a week). The injected C-hMOS were distributed only a fraction in liver but not in heart, lung, spleen or kidney and displayed good biocompatibility. The DOX-delivering C-hMOS significantly suppressed the in vivo tumor growth associated with apoptotic functions. Taken together, the developed C-hMOS nanoparticles can be a promising nanoplatform for drug delivery and in vivo imaging in cancer treatment.
  
  
  
  Multifunctional nanoparticles that combine chemotherapeutic ability with imaging modality comprise promising platform for cancer theranostics. Here we developed a novel theranostic nanoparticle, i.e., carbon-dot created mesoporous hollow silica nanoparticle, to offer unique merit for this purpose. The in vitro and in vivo findings to support this include: i) carbon dots with 1-2nm size in situ generated discretely and uniformly within silica network, ii) hollow and mesoporous structure effective for loading of DOX at high content, iii) release behavior of DOX in a sustainable and pH-dependent manner, iv) chemotherapeutic efficacy in killing cancer cells and suppressing tumor growth through DOX delivery, and v) carbon dot induced multi-color fluorescence imaging within cells and tumor tissues. These collective multifaceted properties may facilitate the novel carbon dot nanocarriers to be a potential candidate for delivering anticancer drug and non-invasive imaging in cancer treatment.
authors.affiliation: Institute of Tissue Regeneration Engineering, Dankook University, Cheonan 330-714, Republic of Korea; Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714, Republic of Korea.
authors.forename: Min Sil
authors.initials: MS
authors.lastname: Kang
authors.affiliation: Institute of Tissue Regeneration Engineering, Dankook University, Cheonan 330-714, Republic of Korea; Department of Nanobiomedical Science and 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: Institute of Tissue Regeneration Engineering, Dankook University, Cheonan 330-714, Republic of Korea; Department of Nanobiomedical Science and 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: Institute of Tissue Regeneration Engineering, Dankook University, Cheonan 330-714, Republic of Korea; Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714, Republic of Korea.
authors.forename: Joong-Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Institute of Tissue Regeneration Engineering, Dankook University, Cheonan 330-714, Republic of Korea; Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714, Republic of Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan 330-714, Republic of Korea.
authors.forename: Kapil D
authors.initials: KD
authors.lastname: Patel
authors.affiliation: Institute of Tissue Regeneration Engineering, Dankook University, Cheonan 330-714, Republic of Korea; Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714, Republic of Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan 330-714, Republic of Korea. Electronic address: kimhw@dku.edu.
authors.forename: Hae-Won
authors.initials: HW
authors.lastname: Kim
mesh_terms: D000818:Animals; D002244:Carbon / Q000737:chemistry / Q000494:pharmacology; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000188:drug therapy; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry / Q000494:pharmacology; D000068936:Theranostic Nanomedicine / Q000379:methods; D041623:Tomography, Optical Coherence; D023041:Xenograft Model Antitumor Assays
chemical_list: D004337:Drug Carriers; D002244:Carbon; D012822:Silicon Dioxide; D004317:Doxorubicin
keywords: Carbon dots; Chemotherapy; Hollow nanoparticles; Mesoporous silica; Optical imaging; Tumor suppression