Jaemoon Yang

Multifunctional Nanoparticles for Combined Doxorubicin and Photothermal Treatments

To facilitate combined doxorubicin and photothermal treatments, we developed doxorubicin-loaded poly(lactic-co-glycolic acid)-gold half-shell nanoparticles (DOX-loaded PLGA-Au H-S NPs) by depositing Au films on DOX-loaded PLGA NPs. As the PLGA NPs biodegraded, DOX was released, and heat was locally generated upon near-infrared (NIR) irradiation due to NIR resonance of DOX-loaded PLGA H-S NPs. Compared with chemotherapy or photothermal treatment alone, the combined treatment demonstrated a synergistic effect, resulting in higher therapeutic efficacy and shorter treatment times. Since our NPs selectively deliver both heat and drug to tumorigenic regions, they may improve the therapeutic effectiveness with minimal side effects.

Convertible Organic Nanoparticles for Near-Infrared Photothermal Ablation of Cancer Cells†

Well-designed photothermal nanomaterials have attractedthe interest of many scientists pursuing a better means toaccurately diagnose cancer and assess the efficacy of treat-ment, because these materials enable therapies in which thetumor region is pin-pointed with a laser-guided light sourcewithout surgical intervention.

Hollow Silica Nanocontainers as Drug Delivery Vehicles

Novel hollow silica nanoparticles (HSNPs) for drug delivery vehicles were synthesized using silica-coated magnetic assemblies, which are composed of a number of Fe(3)O(4) nanocrystals, as templates. The core cavity was obtained by removal of Fe(3)O(4) phase with hydrochloric acid and subsequent calcination at a high temperature. HSNPs were modified by amine in order to introduce positive surface charge and further PEGylated for increased solubility in aqueous medium. Doxorubicin as a model drug was loaded into the HSNPs, and notable sustained drug release from HSNPs was demonstrated.

pH-triggered drug-releasing magnetic nanoparticles for cancer therapy guided by molecular imaging by MRI.

E.-K. Lim , Prof. S. Haam Department of Chemical and Biomolecular EngineeringYonsei UniversitySeoul 120-749, Republic of Korea E-mail: haam@yonsei.ac.kr Prof. .-M. Y Huh , Prof. J. ang , Y Prof. J.-S. Suh Department of RadiologyYonsei UniversitySeoul 120-752, Republic of KoreaE-mail: jss@yuhs.ac Prof. .-M. Y Huh , Prof. J. ang , Y Prof. J.-S. Suh , Prof. S. Haam YUHS-KRIBB Medical Convergence Research InstituteSeoul 120-752, Republic of Korea Prof. .-M. Y Huh , Prof. J.-S. Suh Severance Biomedical Science Institute(SBSI)Seoul 120-752, Republic of Korea Prof. K. Lee Department of ChemistryKorea UniversitySeoul 136-701, Republic of Korea

Prostate cancer cell death produced by the co-delivery of Bcl-xL shRNA and doxorubicin using an aptamer-conjugated polyplex

We investigated the synergism between shRNAs against Bcl-xL and doxorubicin (DOX) using aptamer-conjugated polyplexes (APs) in combination cancer therapy. Synergistic and selective cancer cell death was achieved by AP-mediated co-delivery of very small amounts of DOX and Bcl-xL-specific shRNA, which simultaneously activated an intrinsic apoptotic pathway. A branched polyethyleneimine (PEI) was grafted to polyethylene glycol (PEI-PEG) to serve as a vehicle for shRNA delivery, and its surface was further conjugated with an anti-PSMA aptamer (APT) for the selective delivery of APs to prostate cancer cells that express prostate-specific membrane antigens (PSMA) on their cell surface. The APs were finally obtained after intercalation of DOX to form shRNA/PEI-PEG-APT/DOX conjugates. Cell viability assays and FACS analysis of GFP expression against PC3 (PSMA deficient) and LNCaP (PSMA overexpressed) cells demonstrated that the synthesized APs inhibited the growth of PSMA-abundant prostate cancer cells with strong cell selectivity. Consequently, IC(50) values of APs loaded with both DOX and shRNA were approximately 17-fold less than those for the simple mixture of shRNA plus drug (shRNA/Lipofectamine + DOX). These results suggest that AP-mediated co-delivery of an anti-cancer drug and shRNA against Bcl-xL may widen the therapeutic window and allow for the selective destruction of cancer cells.

Antibody conjugated magnetic PLGA nanoparticles for diagnosis and treatment of breast cancer

DOX–magnetic PLGA nanoparticles conjugated with well-tailored antibodies were synthesized for the detection and therapy of breast cancer. Magnetic nanocrystals embedded in polymeric nanoparticles did not inhibit the nanoparticle formulation or drug release kinetics. The multimodal nanoparticles demonstrated remarkable cancer cell affinity and ultrasensitivity via magnetic resonance imaging. Furthermore, the loaded anticancer drugs were released and sustained for three weeks.

Smart Drug‐Loaded Polymer Gold Nanoshells for Systemic and Localized Therapy of Human Epithelial Cancer

Near-infrared-light-sensitive multifunctional smart drug-loaded polymer gold nanoshells are fabricated as advanced prototypes, composed of chemotherapeutic agents (therapeutic antibody and anticancer drug-loaded polymeric nanoparticles) for systemic chemotherapy of human epithelial cancer and a polymer-based gold nanoshell for localized photothermal treatment by NIR light.

Fluorescent magnetic nanohybrids as multimodal imaging agents for human epithelial cancer detection

Cetuximab conjugated fluorescent magnetic nanohybrids (CET-FMNHs) were synthesized for detection of human epithelial cancer via magnetic resonance (MR) and optical imaging. Spherical FMNHs consist of MnFe(2)O(4) magnetic nanocrystals encapsulated in pyrene-labeled PCL-b-PMAA as a surfactant prepared by a nano-emulsion method. FMNHs demonstrated excellent colloidal stability and biocompatibility for biomedical application. Antibody conjugated fluorescent magnetic nanohybrids (CET-FMNHs) served as effective agents for both magnetic resonance (MR) and fluorescence optical imaging of cancer cell lines.

Targetable Gold Nanorods for Epithelial Cancer Therapy Guided by Near-IR Absorption Imaging

Well-designed nanoparticle-mediated, image-guided cancer therapy has attracted interest for increasing the efficacy of cancer treatment. A new class of smart theragnostic nanoprobes employing cetuximab (CET)-conjugated polyethylene glycol (PEG)ylated gold nanorods (CET-PGNRs) is presented; these nanoprobes target epithelial cancer cells using near-infrared light. The cetyltrimethylammonium bromide bilayer on GNRs is replaced with heterobifunctional PEG (COOH-PEG-SH) to serve as a biocompatible stabilizer and to increase specificity. The carboxylated GNRs are further functionalized with CET using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC-NHS) chemistry. To assess the potential of such GNRs, their optical properties, biocompatibility, colloidal stability, in vitro/in vivo binding affinities for cancer cells, absorption imaging, and photothermal therapy effects are investigated. CET-PGNRs exhibit excellent tumor targeting ability and strong potential for simultaneous absorption imaging and photothermal ablation of epithelial cancer cells.

Consecutive Targetable Smart Nanoprobe for Molecular Recognition of Cytoplasmic microRNA in Metastatic Breast Cancer

We report smart nanoprobe, hyaluronic acid (HA)-based nanocontainers containing miR-34a beacons (bHNCs), for the intracellular recognition of miR-34a levels in metastatic breast cancer cells, which is distinct from the imaging of biomarkers such of cell membrane receptors such as HER2. In this study, we demonstrate that a nanoscale vesicle that couples a targeting endocytic route, CD44, and a molecular imaging probe enables the efficient detection of specific miRNAs. Furthermore, bHNCs showed no cytotoxicity and high stability due to the anchored HA molecules on the surface of nanocontainers, and enables the targeted delivery of beacons via CD44 receptor-mediated endocytosis. In vitro and in vivo optical imaging using bHNCs also allow the measurement of miR-34a expression levels due to the selective recognition of the beacons released from the internalized bHNCs. We believe that the technique described herein can be further developed as a cancer diagnostic as well as a miRNA-based therapy of metastatic cancer.