Inhibition of Autophagy Promotes the Elimination of Liver Cancer Stem Cells by CD133 Aptamer-Targeted Delivery of Doxorubicin.

Doxorubicin is the most frequently used chemotherapeutic agent for the treatment of hepatocellular carcinoma. However, one major obstacle to the effective management of liver cancer is the drug resistance derived from the cancer stem cells. Herein, we employed a CD133 aptamer for targeted delivery of doxorubicin into liver cancer stem cells to overcome chemoresistance.

A Detailed Protein-SELEX Protocol Allowing Visual Assessments of Individual Steps for a High Success Rate.

As a nucleic acid alternative to traditional antibody, aptamer holds great potential in various fields of biology and medicine such as targeted gene therapy, drug delivery, bio-sensing, and laboratory medicine. Over the past decades, the conventional Systematic Evolution of Ligands by Exponential Enrichment (SELEX) method has undergone dramatic modifications and improvements owing to developments in material sciences and analytical techniques. However, many of the recently developed strategies either require complex materials and instruments or suffer from low efficiency and high failure rates in the selection of desired aptamers.

Development of DNA aptamers targeting low-molecular-weight amyloid-β peptide aggregates in vitro.

We have developed a novel functional nucleic acid aptamer to amyloid-β peptide 1-40 (Aβ1-40) and investigated its potential to detect Aβ peptide fragments in neuropathologically confirmed Alzheimer brain hippocampus tissues samples. Our results demonstrate that the aptamer candidate RNV95 could detect tetrameric/pentameric low-molecular-weight Aβ aggregates in autopsy hippocampal tissue from two neuropathologically confirmed Alzheimer disease cases. Although these are preliminary observations, detailed investigations are under way.

Development of Cell-Specific Aptamers: Recent Advances and Insight into the Selection Procedures.

Systematic evolution of ligands by exponential enrichment (SELEX) is an established procedure for developing short single-stranded nucleic acid ligands called aptamers against a target of choice. This approach has also been used for developing aptamers specific to whole cells named Cell-SELEX. Aptamers selected by Cell-SELEX have the potential to act as cell specific therapeutics, cell specific markers or cell specific drug delivery and imaging agents.

Transforming doxorubicin into a cancer stem cell killer via EpCAM aptamer-mediated delivery.

Chemotherapy-resistant cancer stem cells (CSCs) are a major obstacle to the effective treatment of many forms of cancer. To overcome CSC chemo-resistance, we developed a novel system by conjugating a CSC-targeting EpCAM aptamer with doxorubicin (Apt-DOX) to eliminate CSCs. Incubation of Apt-DOX with colorectal cancer cells resulted in high concentration and prolonged retention of DOX in the nuclei.

Next-Generation Nucleic Acid Aptamers with Two-Base-Modified Nucleotides Have Improved Binding Affinity and Potency.

Twice as apt: Nucleic acid aptamers with high binding affinity, specificity, epitope coverage and nuclease resistance were developed by using libraries containing oligonucleotides in which two bases in the pyrimidine nucleotide had been modified.

Challenges and opportunities for siRNA-based cancer treatment.

As one of the life-threatening diseases involving multi-step genetic and epigenetic disorders, cancer has long been a dynamic research area for siRNA-based therapy as half of the current siRNA-based clinical trials are involved in oncology. However, despite consistent enthusiasm in the academic world, siRNA-based cancer treatment still faces obstacles and difficulties in clinical development. In this article, we discuss key challenges facing siRNA-based cancer treatment revealed from recent clinical and preclinical studies, including chemical modification, tumour penetration, endosomal escape, target selection and off-target effects.

EpCAM Aptamer-mediated Survivin Silencing Sensitized Cancer Stem Cells to Doxorubicin in a Breast Cancer Model.

Understanding the molecular basis of drug resistance and utilising this information to overcome chemoresistance remains a key challenge in oncology. Here we report that survivin, a key protein implicated in drug resistance, is overexpressed in cancer stem cell pool of doxorubicin-resistant breast cancer cells. Moreover, by utilising an active targeting system consisting of an RNA aptamer targeted against the epithelial cell adhesion molecule and a Dicer substrate survivin siRNA, we could deliver a high dose of the siRNA to cancer stem cells in xenograft tumours.

Cancer stem cell targeted therapy: progress amid controversies.

Although cancer stem cells have been well characterized in numerous malignancies, the fundamental characteristics of this group of cells, however, have been challenged by some recent observations: cancer stem cells may not necessary to be rare within tumors; cancer stem cells and non-cancer stem cells may undergo reversible phenotypic changes; and the cancer stem cells phenotype can vary substantially between patients. Here the current status and progresses of cancer stem cells theory is illustrated and via providing a panoramic view of cancer therapy, we addressed the recent controversies regarding the feasibility of cancer stem cells targeted anti-cancer therapy.

Aptamer-mediated cancer gene therapy.

Cancer as a genetic disorder is one of the leading causes of death worldwide. Conventional anticancer options such as chemo- and/or radio-therapy have their own drawbacks and could not provide a cure in most cases at present. More effective therapeutic strategies with less side effects are urgently needed.

Aptamers as theranostic agents: modifications, serum stability and functionalisation.

Aptamers, and the selection process known as Systematic Evolution of Ligands by Exponential Enrichment (SELEX) used to generate them, were first described more than twenty years ago. Since then, there have been numerous modifications to the selection procedures. This review discusses the use of modified bases as a means of enhancing serum stability and producing effective therapeutic tools, as well as functionalising these nucleic acids to be used as potential diagnostic agents.

Nucleic acid aptamers as novel class of therapeutics to mitigate Alzheimer's disease pathology.

Deposition of amyloid-β (Aβ) peptides in the brain is a central event in the pathogenesis of Alzheimer's disease (AD), which makes Aβ peptides a crucial target for therapeutic intervention. Significant efforts have been made towards the development of ligands that bind to Aβ peptides with a goal of early detection of amyloid aggregation and the neutralization of Aβ toxicity. Short single-stranded oligonucleotide aptamers bind with high affinity and specificity to their targets.