ABSTRACT
ZnO quantum dots (QDs) were synthesized with polymer shells, coordinated with Gd(3+) ions and adsorbed doxorubicin (DOX) together to form a new kind of multifunctional ZnO-Gd-DOX nanoplatform. Such pH sensitive nanoplatforms were shown to release DOX to cancer cells in vitro and to mouse tumors in vivo, and reveal better specificity and lower toxicity than free DOX, and even better therapeutic efficacy than an FDA approved commercial DOX-loading drug DOX-Liposome Injection (DOXIL, NDA#050718). The ZnO-Gd-DOX nanoplatforms exhibited strong red fluorescence, which benefited the fluorescent imaging on live mice. Due to the special structure of ZnO-Gd-DOX nanoparticles, such nanoplatforms possessed a high longitudinal relaxivity r1 of 52.5 mM(-1) s(-1) at 0.55 T, which was superior to many other Gd(3+) based nanoparticles. Thus, both fluorescence labeling and magnetic resonance imaging could be applied simultaneously on the tumor bearing mice along with drug delivery. After 36 days of treatment on these mice, ZnO-Gd-DOX nanoparticles greatly inhibited the tumor growth without causing any appreciable abnormality in major organs. The most important merit of ZnO-Gd-DOX was that such a nanoplatform was biodegraded completely and showed no toxic side effects after H&E (hematoxylin and eosin) staining of tumor slices and ICP-AES (inductively coupled plasma atomic emission spectrometry) bioanalyses.
Subject(s)
Antineoplastic Agents/chemistry , Contrast Media/chemistry , Doxorubicin/analogs & derivatives , Drug Carriers/chemistry , Fluorescent Dyes/chemistry , Gadolinium/chemistry , Neoplasms, Experimental/diagnostic imaging , Quantum Dots/chemistry , Zinc Oxide/chemistry , Animals , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Apoptosis/drug effects , Cell Line, Tumor , Cell Survival , Doxorubicin/adverse effects , Doxorubicin/chemistry , Doxorubicin/therapeutic use , Humans , Magnetic Resonance Imaging , Methacrylates/chemistry , Mice, Nude , Neoplasm Transplantation , Neoplasms, Experimental/drug therapy , Particle Size , Polyethylene Glycols/adverse effects , Polyethylene Glycols/chemistry , Polyethylene Glycols/therapeutic use , Surface Properties , Tissue DistributionABSTRACT
We report a novel method for synthesizing water-dispersible silicon nanoparticles (Si NPs) with a simple one-step procedure using mild reagents (3-aminopropyl) trimethoxysilane (APTES) and ascorbate sodium (AS). This is the first report of "green" synthesis of Si NPs on a large scale and at low cost. The method involves a quick reaction in a commonly used round bottom flask at room temperature and pressure without additional treatment and any special equipment. The as-prepared Si NPs have an average diameter of 2 nm and an emission band at 530 nm with a full width at half maximum height (FWHM) of 70 nm and a quantum yield (QY) of 0.21. Moreover, the fluorescence lifetime of these Si NPs is much longer than that of native fluorophores in living cells. Therefore, these Si NPs allow effective imaging of living cells with a fluorescence lifetime imaging microscope (FLIM). Using the time gating model in FLIM, an excellent image was obtained in which the auto-fluorescence interference of cellular fluorophores was suppressed demonstrating that the Si NPs are promising probes for cell imaging particularly using the FLIM technique.
