Bispecific therapeutic aptamers for targeted therapy of cancer: a review on cellular perspective

Aptamers (Aps), as short single-strand nucleic acids, can bind to their corresponding molecular targets with the high affinity and specificity. In comparison with the monoclonal antibodies (mAbs) and peptides, unique physicochemical and biological characteristics of Aps make them excellent targeting agents for different types of cancer molecular markers (CMMs). Much attention has been paid to the Ap-based multifunctional chimeric and therapeutic systems, which provide promising outcomes in the targeted therapy of various formidable diseases, including malignancies. In the Ap-based chimeric systems, a targeting Ap is conjugated to another therapeutic molecule (e.g., siRNA/miRNA, Ap, toxins, chemotherapeutic agents, DNAzyme/ribozymes) with a capability of binding to a specific cell surface receptor at the desired target site. Having been engineered as multifunctional nanosystems (NSs), Ap-based hybrid scaffolds can be used to concurrently target multiple markers/pathways in cancerous cells, causing drastic inhibitory effects on the growth and the progression of tumor cells. Multi/bispecific Aps composed of two/more Aps provide a versatile tool for the optimal and active targeting of cell surface receptor(s) with markedly high affinity and avidity. Targeting the optimum activity of key receptors and dominant signaling pathways in the activation of immunity, the multi/bispecific Ap-based therapeutics can also be used to enhance the antitumor activity of the immune system. Further, the bispecific systems can be designed to induce cytotoxicity in a heterogeneous population of cancer cells with different CMMs. In this review, we provide some important insights into the construction and applications of the Ap-based chimeric NSs and discuss the multifunctional Ap chimera and their effects on the signaling pathways in cancer.