ABSTRACT
Dual surfaced dumbbell-like gold magnetic nanoparticles (Au-Fe3O4) were synthesized for targeted aptamers delivery. Their unique biological properties were characterized as a smart photo-controlled drug carrier. DNA aptamers targeting vascular endothelial growth factor (VEGF) were assembled onto the surface of Au-Fe3O4 by electrostatic absorption. The binding capacity of the nanoparticles with VEGF aptamers was confirmed by gel electrophoresis. The targeted recognization of ovarian cancer cells by the aptamers-functionalized Au-Fe3O4 nanoparticles (Apt-Au-Fe3O4 NPs) was observed by confocal microscopy. Apt-Au-Fe3O4 was found to bind with SKOV-3 ovarian cancer cells specifically, leading to marked intracellular release of aptamers upon plasmon-resonant light (605nm) radiation, and to enhance the in vitro inhibition against tumor cell proliferation. The results show high potential of Apt-Au-Fe3O4as a targeted cancer hyperthermia carrier by remote control with high spatial/temporal resolution.
Subject(s)
Magnetite Nanoparticles , Aptamers, Nucleotide , Gold , Humans , Magnetics , Neoplasms , Vascular Endothelial Growth Factor AABSTRACT
Efficient delivery of small interfering RNAs (siRNAs) to the targeted cells has remained a significant challenge in clinical applications. In the present study, we developed a novel aptamer-siRNA chimera delivery system mediated by cationic Au-Fe3O4 nanoparticles (NPs). The chimera constructed by VEGF RNA aptamer and Notch3 siRNA was bonded with heterogeneous Au-Fe3O4 nanoparticles by electrostatic interaction. The obtained complex exhibited much higher silencing efficiency against Notch3 gene compared with chimera alone and lipofectamine-siRNA complex, and improved the antitumor effects of the loaded chimera. Moreover, the efficient delivery of the chimera by Au-Fe3O4 NPs could reverse multi-drug resistance (MDR) of ovarian cancer cells against the chemotherapeutic drug cisplatin, indicating its potential capability for future targeted cancer therapy while overcoming MDR.
Subject(s)
Aptamers, Nucleotide , Drug Delivery Systems/methods , Drug Resistance, Multiple/drug effects , Drug Resistance, Neoplasm/drug effects , Gold/chemistry , Magnetite Nanoparticles/chemistry , Neoplasm Proteins/antagonists & inhibitors , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Aptamers, Nucleotide/chemistry , Aptamers, Nucleotide/pharmacology , Cell Line, Tumor , Female , Humans , Neoplasm Proteins/biosynthesis , Ovarian Neoplasms , Vascular Endothelial Growth Factor A/biosynthesisABSTRACT
Targeted nanocarriers may offer a new approach to improve the efficacy and tolerability of cisplatin, which are commonly used to treat cancers as a first line chemotherapy for most types of cancer. In the present study, we have developed EGFR-targeted albumin-cisplatin nanoparticles for tumor targeted delivery of cisplatin. The cisplatin NPs were conjugated with EGFR aptamer, which binded to Hela cells specifically, then taken up by tumor cells through receptor mediated endocytosis. The aptamers accumulate in the tumor and interact with the receptor on the surface of Hela cells, successfully blocked EGF-induced EGFR phosphorylation, exerting its targeting and therapy function. Here we demonstrate that the EGFR aptamer functioned NPs enhanced in vitro antitumor effects and markedly improved its tolerability and in vivo efficacy when compared with free cisplatin and other single treatment. Furthermore, the Apt-Pt NPs treatment resulted in reduced systemic and nephrotoxicity, validated by decreased biodistribution of platinum in the major organs as quantified by ICP-MS. The Apt-Pt NPs provides a remarkable improvement in the drug therapeutic efficacy and tolerability in vivo, and will be generalized as a principle for development of novel nanocarriers for targeted tumor therapy.
