as-1411 and Uterine-Cervical-Neoplasms

Nanoparticles offer targeted delivery of drugs with minimal toxicity to surrounding healthy tissue and have great potential in the management of human papillomavirus (HPV)-related diseases. We synthesized lipid-modified AS1411 aptamers capable of forming nanoaggregates in solution containing Mg

Topics: Antineoplastic Agents; Antiviral Agents; Aptamers, Nucleotide; Cell Proliferation; Drug Delivery Systems; Female; HeLa Cells; Humans; Oligodeoxyribonucleotides; Uterine Cervical Neoplasms

Nucleic acid aptamers can specifically bind to target molecules on the cell membrane that mediate their entrance into the cells. Their small size, high binding affinity, specificity, good biocompatibility, stability and low immunogenicity make them ideal drug delivery systems for cancer therapy. These biopharmaceuticals have potential for the delivery of anticancer compounds to diseased tissues, increasing their effectiveness while mitigating the off-target toxicity towards healthy cells. Herein, we have studied two quadruplex-forming DNA sequences derived from the nucleolin-targeted aptamer AS1411 as supramolecular carriers for the cancer-selective delivery of acridine orange derivatives (C

Topics: Acridine Orange; Aptamers, Nucleotide; Cell Line; Cell Survival; Drug Delivery Systems; Female; G-Quadruplexes; Humans; Ligands; Oligodeoxyribonucleotides; Uterine Cervical Neoplasms

Spherical nucleic acid (SNA) constructs are promising new single entity materials, which possess significant advantages in biological applications. Current SNA-based drug delivery system typically employed single-layered ss- or ds-DNA as the drug carriers, resulting in limited drug payload capacity and disease treatment. To advance corresponding applications, we developed a novel DNA-programmed polymeric SNA, a long concatamer DNA polymer that is uniformly distributed on gold nanoparticles (AuNPs), by self-assembling from two short alternating DNA building blocks upon initiation of immobilized capture probes on AuNPs, through a supersandwich hybridization reaction. The long DNA concatamer of polymeric SNA enables to allow high-capacity loading of bioimaging and therapeutics agents. We demonstrated that both of the fluorescence signals and therapeutic efficacy were effectively inhibited in resultant polymeric SNA. By further modifying with the nucleolin-targeting aptamer AS1411, this polymeric SNA could be specifically internalized into the tumor cells through nucleolin-mediated endocytosis and then interact with endogenous ATP to cause the release of therapeutics agents from long DNA concatamer via a structure switching, leading to the activation of the fluorescence and selective synergistic chemotherapy and photodynamic therapy. This nanostructure can afford a promising targeted drug transport platform for activatable cancer theranostics.

Topics: Adenosine Triphosphate; Antineoplastic Agents; Aptamers, Nucleotide; Chlorophyllides; DNA; Doxorubicin; Drug Carriers; Drug Liberation; Female; Fluorescence; Gold; HeLa Cells; Humans; Light; Metal Nanoparticles; Microscopy, Confocal; Nucleic Acid Hybridization; Oligodeoxyribonucleotides; Photosensitizing Agents; Porphyrins; Singlet Oxygen; Theranostic Nanomedicine; Uterine Cervical Neoplasms

AS1411 is an antiproliferative DNA aptamer, which binds the ubiquitous protein, nucleolin. In this study, we show that constitutive overexpression of nucleolin confers increased sensitivity to the growth inhibitory effects of AS1411. HeLa cells overexpressing nucleolin have an increased growth rate and invasiveness relative to control cells. Nucleolin overexpressing cells demonstrate increased growth inhibition in response to the AS1411 treatment, which correlates with increased apoptosis and cell cycle arrest, when compared to non-transfected cells. AS1411 induces nucleolin expression at the RNA and protein level in HeLa cells, suggesting a feedback loop with important implications for the clinical use of AS1411.

Topics: Aptamers, Nucleotide; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Cell Survival; Feedback, Physiological; Female; Gene Expression Regulation, Neoplastic; HeLa Cells; Humans; Nucleolin; Oligodeoxyribonucleotides; Phosphoproteins; RNA-Binding Proteins; Transfection; Up-Regulation; Uterine Cervical Neoplasms

Herein, one multifunctional AS1411-functionalized fluorescent gold nanoparticles (named NAANPs) is synthesized and successfully applied for both targeted cancer cell imaging and efficient photodynamic therapy (PDT). The NAANPs are obtained by functionalizing the gold nanoparticles with AS1411 aptamer and then bound with one porphyrin derivative N-methylmesoporphyrin IX (NMM). Using HeLa cells over expressing nucleolin as representative cancer cells, the formed NAANPs can target to the cell surface via the specific AS1411-nucleolin interaction, which can discriminate the cancer cells from normal ones (e.g. HEK293) unambiguously. That the fluorescence intensity of NMM increased significantly upon binding to AS1411 G-quadruplex makes the NAANPs appropriate fluorescence reagent for cell imaging. Meanwhile, NMM can also be used as a photosensitizer, thus irradiation of the NAANPs by the white light from a common electric torch can lead to efficient production of cytotoxic reactive oxygen species for establishing a new type of PDT to cancer cells. Gold nanoparticles play the roles of both carrier and enhancer of the functional groups onto the cells. In addition, they not only possess inherently certain cytotoxicity to the cancer cells, but also boost the cellular uptake of the fluorescent groups. As a result, the efficiency of both the targeted cell imaging and PDT could be ensured.

Topics: Aptamers, Nucleotide; Cell Proliferation; Female; Fluorescent Dyes; Gold; Humans; Light; Metal Nanoparticles; Oligodeoxyribonucleotides; Photochemotherapy; Protoporphyrins; Tumor Cells, Cultured; Uterine Cervical Neoplasms