Novel multifunctional nanodevices for cancer diagnosis and therapy

Abstract

Cancer is a major cause for human deaths. Owing to the lack of highly sensitive diagnostic techniques, early diagnosis of cancer is one of the challenges to improve the survival rate of cancer patients. On the other hand, commonly used treatments for cancer, including surgery, chemotherapy and radiotherapy, have respective limitations. Nanotechnology has revolutionized the detection and treatment of diseases, including cancer. Many nanoparticles are explored in oncology because of their unique properties. However, nanoparticles with single function may not meet clinical requirements. Therefore, multifunctional nanodevices, which integrate different nanocomponents into one nanosystem to perform diagnostic, therapeutic and possibly treatment-monitoring functions, are powerful tools to overcome the obstacles and lower cancer mortality. The aim of this project was to design and fabricate different types of multifunctional nanodevices with different core functions and to investigate their performance in cancer targeting, detection, imaging, and treatment. Different techniques were developed to make core-shell, core-satellite, core-shell-satellite and yolk-shell structured nanoparticles as multifunctional nanodevices. Gold nanoparticles and magnetic nanoparticles have fascinating physical and chemical properties. Various gold nanoparticles of different sizes and shapes were produced by different methods. Gold nanorods were synthesized and a porous silica shell was then formed on them for gold nanorod/mesoporous silica core-shell structured nanoparticles (AuNR@mSiO2). Highly branched gold-silver nanoparticles were synthesized with a folic acid-conjugated chitosan (FA-CS) shell to form metal-polymer nanoparticles (Au-Ag@FA-CS). Monodispersed Fe3O4 nanoparticles were coated with chitosan-crosslinked poly(ethylene oxide)100-poly(propylene oxide)65-poly(ethylene oxide)100 (Pluronic F127) shell to form nanocapsules (Fe3O4@F127-chitosan). Silica/gold (sSiO2@Au) and mesoporous silica/gold (mSiO2@Au) nanoparticles were fabricated by depositing numerous gold nanoparticles on solid or mesoporous silica nanoparticles to form core-satellite structured nanoparticles. Numerous gold nanoparticles were deposited on core-shell AuNR@mSiO2 nanoparticles to form core-shell-satellite structured nanoparticles. Selective etching was developed for AuNR@mSiO2 nanoparticles to form yolk-shell AuNR@void@mSiO2 nanoparticles. Rhodamine 6G (as a Raman reporter or fluorescence agent), anti-cancer drugs (doxorubicin) and plasmid DNA (encoding enhanced green fluorescence protein) were encapsulated in the porous silica or polymer shell of nanoparticles to form multifunctional nanodevices. The metal nanocomponents in these nanodevices provided light-scattering or magnetic property as imaging contrast agents or surface enhanced Raman scattering (SERS) tags. They could also generate heat under external stimulus to trigger the release of therapeutic agents from nanoparticles. While having the enhanced permeability and retention (EPR) effect for passive targeting, these nanodevices through conjugating targeting ligands could achieve active targeting for selective imaging, detection and treatment of targeted cancer cells. These nanodevices showed high biocompatibility by fibroblast cells (3T3), breast cancer cells (MCF-7) and folate receptor-overexpressed cervical cancer cells (Hela). The targeting ability, intracellular uptake, imaging and detection capability of these nanodevices in Hela and MCF-7 cells were systematically investigated. The efficiency of chemotherapy, photothermal and combined chemo-photothermal therapies provided by these nanodevices were assessed. Results showed these nanodevices could provide specific therapy to targeted cells and caused cell death. Therefore, the combination of metal nanoparticles, polymers, silica, therapeutic drugs and targeting ligands produced robust and efficient multifunctional nanodevice to accomplish sensitive cancer diagnosis, imaging and effective cancer treatment.