Abstract

Simple SummaryDNA 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.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.

Highlights

  • According to Globacon 2018 [1,2], cancer, the second leading cause of death, claimed the lives of approximately 9.6 million people worldwide

  • The results showed that this system promises to have more efficient therapy and tumor treatment to decrease the adverse effects of cardiotoxicity caused by Dox

  • The obtained results showed that minicircle DNA encapsulated micelleplexes into in vitro tumor spheroid models with specific kinetic and show enhanced gene expression in comparison to other nanocarriers

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Summary

Introduction

According to Globacon 2018 [1,2], cancer, the second leading cause of death, claimed the lives of approximately 9.6 million people worldwide. Hybridization chain reaction (HCR) accumulated higher encapsulated prodrugs from a drug labeled probe and induced their conversion and uptake into cisplatin in cells for selective tumor targeting using this strategy [38] Another type of DNA assembly nanosystems designed by a group of researchers. Present literature mentioned that nanoflower inorganic nanoparticles have a spherical shape and increased the concentration of drug at the malignant site [50,51] They developed AS1411/magnetic nanoparticles for targeted TMPyP4 delivery in this type of non-stimuli inorganic nanoparticle method. The application of external stimuli has several advantages for targeting delivery to tumors: (I) the location and intensity of applied stimuli could be precisely controlled; (II) the stimuli can be added or removed based on available treatment requirements; (III) several different types of stimuli could be used for multifunction in cancer theranostics; (IV) the possibility to provide continuous or multi-times stimuli for drug therapy and delivery [65]. Cationic polymer induces membrane fusion at endosomal pH, Improved anti-cancer property in murine tumor model, Increased gene transfection to hepatocytes

Ultrasound Responsive Nanocarriers
Magnetic Field Triggered Therapy
Thermo-Responsive Nanocarriers Applied for Diagnosis and Treatment of Cancer
Light-Responsive Nanocarriers Applied for Diagnosis and Treatment of Cancer
Advancement in Endogenous Stimuli Sensitive DNA Based Smart Nanocarriers
Oligonucleotide Responsive Nanocarriers
Multiples and Molecular Biomarker Responsive Nanocarriers
DNA Based Hybrid Nanocarriers System for Cancer Targeting
Synthesis Strategy of Self-Assembled DNA Hydrogel
Synthesis Strategy of DNA Origami-Based Nanostructures
Synthesis Strategy of Smart Functionalized DNA Supramolecular Nanostructures
Synthesis of DNA Nanowires
Synthesis of Smart DNA-Lipids Nanostructures
Synthesis Method
Findings
Potential Immuno-Modulatory Effect of DNA-Based Nanostructures
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