DNA Based and Stimuli-Responsive Smart Nanocarrier for Diagnosis and Treatment of Cancer: Applications and Challenges

SIMPLE SUMMARY: DNA based and stimuli-responsive smart nano-carrier system can efficiently deliver encapsulated cargos in response to various driving thresholds. The conditional release of encapsulated carriers via modifications in the dynamic structure of DNA in response to tumor microenvironment has led to the specific delivery of active agents to the tumors. Therefore, specific drug delivery enhances the therapeutic efficacy and decreases the side effects on the neighboring healthy cells. Despite the great potential for pharmacological applications of the DNA-assisted and pH-sensitive smart nano-carriers, some challenges should be addressed before clinical transition. Since the therapeutic efficacies of DNA based smart nano-carriers have only been investigated in a proof-of-concept manner, the detailed in vivo parameters of the nano-carriers must be investigated and elucidated, including colloidal stability, circulating half-life, immunogenicity, dose-dependent cytotoxicity, pharmacokinetics, and clearance mechanisms. ABSTRACT: The rapid development of multidrug co-delivery and nano-medicines has made spontaneous progress in tumor treatment and diagnosis. DNA is a unique biological molecule that can be tailored and molded into various nanostructures. The addition of ligands or stimuli-responsive elements enables DNA nanostructures to mediate highly targeted drug delivery to the cancer cells. Smart DNA nanostructures, owing to their various shapes, sizes, geometry, sequences, and characteristics, have various modes of cellular internalization and final disposition. On the other hand, functionalized DNA nanocarriers have specific receptor-mediated uptake, and most of these ligand anchored nanostructures able to escape lysosomal degradation. DNA-based and stimuli responsive nano-carrier systems are the latest advancement in cancer targeting. The data exploration from various studies demonstrated that the DNA nanostructure and stimuli responsive drug delivery systems are perfect tools to overcome the problems existing in the cancer treatment including toxicity and compromised drug efficacy. In this light, the review summarized the insights about various types of DNA nanostructures and stimuli responsive nanocarrier systems applications for diagnosis and treatment of cancer.