Tumor-targeted drug delivery with aptamers

Abstract

Cancer is one of the leading causes of death around the world. Tumor-targeted drug delivery is one of the major areas in cancer research. Aptamers exhibit many desirable properties for tumor-targeted drug delivery, such as ease of selection and synthesis, high binding affinity and specificity, low immunogenicity, and versatile synthetic accessibility. Over the last several years, aptamers have quickly become a new class of targeting ligands for drug delivery applications. In this review, we will discuss in detail about aptamer-based delivery of chemotherapy drugs (e.g. doxorubicin, docetaxel, daunorubicin, and cisplatin), toxins (e.g. gelonin and various photodynamic therapy agents), and a variety of small interfering RNAs. Although the results are promising which warrants enthusiasm for aptamer-based drug delivery, tumor homing of aptamer-based conjugates after systemic injection has only been achieved in one report. Much remains to be done before aptamer-based drug delivery can reach clinical trials and eventually the day-to-day management of cancer patients. Therefore, future directions and challenges in aptamer-based drug delivery are also discussed.

Fig. 1

A schematic depiction of SELEX (systematic evolution of ligands by exponential enrichment). The target can be either proteins or cancer cells. For cell-based SELEX, typically the nucleic acid library is first incubated with non-target cells. Only unbound nucleic acids are used for selection against the target cells. Typically, aptamer selection can be completed after 10–20 rounds of selection process. Adapted from [42].

Fig. 2

A QD-Apt-Dox conjugate. A. QD-Apt-Dox is initially “off” as the fluorescence of QD is transferred to Dox and the fluorescence of Dox is quenched by the aptamer, both by fluorescence resonance energy transfer. B. Once QD-Apt-Dox is inside cancer cells, Dox is gradually released from the conjugate and the fluorescence of QD is recovered. C. Microscopy images of PSMA-positive cells after incubation with QD-Apt-Dox. QD and Dox are shown in green and red, respectively. Scale bar: 20 μm. Adapted from [42,48].

Fig. 3

A dual-aptamer (A10 RNA and DUP-1 peptide) probe that can target both PSMA-positive and PSMA-negative cells. The red parts indicate the cells and blue dots represent the stained superparamagnetic iron oxide nanoparticles. Adapted from [53].

Fig. 4

An improved second generation aptamer-siRNA chimera exhibited excellent anti-cancer efficacy in a xenograft model of prostate cancer. A. The first and second generation chimeras. B. Bioluminescence imaging of mice bearing luciferase-expressing PSMA-positive tumors showed significantly lower signal after being treated with the second generation aptamer-siRNA chimera as compared to saline control. C. H&E staining of tumor tissue after treatment showed readily detectable areas of necrosis (asterisks) in the second generation aptamer-siRNA chimera-treated tumors, but not frequently in saline-treated tumors. TUNEL staining was detected in scattered cells throughout the tumor section of each group. Adapted from [78].

Fig. 5

A multifunctional nanoplatform incorporating multiple receptor targeting with different aptamers, multimodality imaging, and multiple therapeutic entities. Not all functional moieties will be necessary and only suitably selected components are needed for each individual application. The various functional moieties may be either on the surface of or encapsulated inside the nanoparticle (NP).