Cell-type-specific, Aptamer-functionalized Agents for Targeted Disease Therapy

Abstract

One hundred years ago, Dr. Paul Ehrlich popularized the “magic bullet” concept for cancer therapy in which an ideal therapeutic agent would only kill the specific tumor cells it targeted. Since then, “targeted therapy” that specifically targets the molecular defects responsible for a patient's condition has become a long-standing goal for treating human disease. However, safe and efficient drug delivery during the treatment of cancer and infectious disease remains a major challenge for clinical translation and the development of new therapies. The advent of SELEX technology has inspired many groundbreaking studies that successfully adapted cell-specific aptamers for targeted delivery of active drug substances in both in vitro and in vivo models. By covalently linking or physically functionalizing the cell-specific aptamers with therapeutic agents, such as siRNA, microRNA, chemotherapeutics or toxins, or delivery vehicles, such as organic or inorganic nanocarriers, the targeted cells and tissues can be specifically recognized and the therapeutic compounds internalized, thereby improving the local concentration of the drug and its therapeutic efficacy. Currently, many cell-type-specific aptamers have been developed that can target distinct diseases or tissues in a cell-type-specific manner. In this review, we discuss recent advances in the use of cell-specific aptamers for targeted disease therapy, as well as conjugation strategies and challenges.

A combined microRNA-based targeted therapeutic approach to eradicate glioblastoma stem-like cells

“…In the past decade, much attention has been focused on RNAbased aptamers that are emerging as safe delivery vehicles for targeted cancer therapeutics [19]. In addition to inhibitory function of selected targets, aptamers raised against transmembrane receptors rapidly internalize into the target cell through recycling of the bound receptor [20].…”

“…In addition to inhibitory function of selected targets, aptamers raised against transmembrane receptors rapidly internalize into the target cell through recycling of the bound receptor [20]. So far, various therapeutic cargoes have been successfully conjugated to aptamers, including anti-cancer drugs, toxins, radionuclides, and short therapeutic RNAs (siRNAs and miRNAs) [19,21,22]. The main advantages for aptamer use in vivo as cell targeting moieties, include the extraordinary high binding specificity, long-term stability, little to no immunogenicity and off target toxicity [23].…”

Reducing Toxicity of Immune Therapy Using Aptamer-Targeted Drug Delivery

“…The short nucleic acid-based aptamers are not expected to elicit significant neutralizing immunity that may become an issue, especially with repeated administration of even humanized antibodies. Aptamers have been used mostly to target nucleic acid-based biologic or therapeutic agents, such as siRNAs, microRNAs, or aptamers, and have been evaluated in preclinical in vitro and in vivo murine models for cancer and HIV (10,11). The use of therapeutic agents in the form of short nucleic acid-based cargo is attractive because conjugation to the targeting ligands, in contrast with conjugation to antibodies or peptides, is a simple procedure involving hybridization of short complementary sequences engineered at the end of the aptamer and its cargo.…”

Development and Characterization of a ssDNA-based Aptamer that Selectively Targets Epithelial Carcinoma Cells

“…Aptamers combine nanomolar range targetbinding affinities with exquisite target specificity, which makes them a versatile tool for diagnostics, in vivo imaging, and targeted therapeutics [12,[26][27][28][29]. Moreover, compared to protein antibodies, aptamers offer unparalleled advantages, as they can be chemically synthesized through a simple process, modified with a variety of functional groups and/or imaging reporters, and elicit little to no immunogenicity or toxicity in preclinical studies [30][31][32][33][34]. Taking advantage of these aptamer properties, our group recently demonstrated that synthetic aptamers can be successfully used as specific probes for flow cytometric analysis in vitro [35,36] and exhibit high tumor penetrating abilities and rapid tumor cells binding in vivo [37].…”