Multifunctional nanoparticles for cancer targeting, detection and chemo-photothermal therapies

Abstract

Theranostics, which are nanoparticles (NPs) capable of cancer detection and treatment, have attracted much attention in recent years. In this investigation, a new type of theranostics based on multifunctional NPs was designed using a combination of different nanostructured materials and then fabricated. Their characteristics and performance were subsequently studied. Compared to their spherical counterparts, gold nanorods (AuNRs) are promising agent for photothermal therapy. Using the capping surfactant CTAB present on the AuNR surface as the template for mesoporous silica formation, a mesoporous silica coating can be made on AuNRs so as to improve the functionality and biocompatibility of AuNRs. Surface enhanced Raman scattering (SERS), which involves strong enhancement of Raman scattering from molecules adsorbed on nanostructured metal surface, can be used as a highly sensitive method for cancer detection. Therefore, based on our previous studies, we developed a facile method to fabricate Au capped AuNR core-mesoporous silica shell (AuNR@mSiO2@Au) NPs, which are expected to not only provide sensitive SERS detection but also combine cancer targeting, imaging and drug delivery and photothermal therapy in a single system. Specifically, a modified seed-mediated method using binary surfactants was employed for AuNR synthesis. AuNRs were then covered by a mesoporous silica shell in a sol-gel and template removal process. Fine Au nanospheres were deposited on the outer surface of AuNR@mSiO2 NPs via electrostatic absorption. The Au nanospheres formed copious hot spots for AuNR@mSiO2@Au NPs for achieving strong SERS signals from Raman reporter molecules (rhodamine 6G) incorporated in the NPs. Furthermore, folic acid was conjugated onto AuNR@mSiO2@Au NPs, allowing them to target folate receptor-overexpressed cancer cells. Doxorubicin hydrochloride (DOX) was loaded into mesopores of NPs as a model anticancer drug. Hela cells which overexpress folate receptor were used in in vitro investigations with MCF-7 cells for control studies. The morphology, structure and composition of AuNR@mSiO2@Au NPs were studied. Drug release from mesoporous channels of AuNR@mSiO2@Au NPs was investigated. Dark-field and fluorescent microscopies were used to assess targeting and imaging capabilities. In vitro SERS signals with targeted cells were measured using Raman spectroscopy. The combined chemo-photothermal effect by AuNR@mSiO2@Au NPs was investigated after laser irradiation. The highly reduced cell viability after near-infrared laser irradiation suggested that the multifunctional nanoparticles could provide effective photothermal effect and control the release of loaded anticancer drug, thereby achieving chemo-photothermal therapies.