Dendrimer– and polymeric nanoparticle–aptamer bioconjugates as nonviral delivery systems: a new approach in medicine

Abstract

Research Highlights Dendrimer-aptamer conjugates Polymer-aptamer conjugates  Delivery aptamers Cancer Aptamers are RNA or DNA oligonucleotides interacting to form unique 3D target conformations with high affinity and specificity, and are emerging as a powerful class of ligands for therapeutic applications. In addition, dendrimers are well-defined nano-sized symmetric polymeric molecules. In this review, we provide an analysis of the use of dendrimers modified with aptamers as nonviral vectors to specifically target tumor cells. Various anticancer agents have been encapsulated with dendrimers complexing with aptamers, including epirubicin, camptothecin, Bcl-xL short hairpin (sh)RNA, and 5-fluorouracil rhodamine-labeled dextran. Other types of polymeric nanoparticle (NP)-aptamer bioconjugates have also been developed and loaded with Pt(IV) derivatives, to target specific tumor cells. Keywords: dendrimer space; aptamers; polymeric nanoparticles; drug delivery. Teaser: We discuss the development of dendrimer-and polymeric nanoparticle-aptamer bioconjugates as a new approach in medicine Aptamer-based tools for therapeutic monitoring for precision therapy Aptamer comes from the Latin 'aptare' meaning to fit together or join, and from the Greek 'meros' meaning part. A nucleic acid aptamer is a short chain of artificial oligonucleotides of RNA or single-stranded DNA with a variable region of ~40-100 nucleotide bases [1]. Their unique, flexible 3D structure, and their high affinity and specificity with ligand-binding capabilities, are strongly related to their sequence. These important characteristics increase their ability to differentiate between targets. In contrast to antibodies, aptamers can bind to functional domains of their cognate target protein (e.g., substrate binding pockets and allosteric sites) ( Figure 1) [2]. Aptamers are considered to be 'smart ligands' and are often named 'nucleic acid antibodies'. The binding between aptamers and user-defined targets occurs through electrostatic interactions, which result in their versatility. The strong binding affinity and exceptional specificity induces a nano-or pico-molar dissociation constant (Kd). Their targets vary from small ions, such as Zn 2+, and large proteins, such as coagulation factor VIII, to whole cells, viruses, and tissues [3]. J o u r n a l P r e -p r o o f

Non-invasive intranasal administration route directly to the brain using dendrimer nanoplatforms: An opportunity to develop new CNS drugs

“…We are convinced and strongly encouraged that this friendly route of administration for the treatment of acute and chronic conditions, for instance for elderly patients, requiring high drug exposure, such as cancers, that require life-long treatment or rapid action. In addition, within the dendrimer space [ 96 ], the use of dendrimers as nanocarriers and as active drugs per se in the oncology domain should be extended based on the following points: 1) to treat brain cancers, which are very difficult to tackle; 2) combination therapy [ 97 ] based on the release of several anticancer drug types, including natural products [ 98 ], siRNAs [ 99 ], mRNAs [ 100 ], antisense [ 101 ] and aptamers [ 102 ]; and 3) dendrimers as anticancer agents [ 103 ]. Importantly, this convenient non-invasive route easily allowed translation from the successes obtained in preclinical studies into human clinical studies as a smart system for all people suffering brain cancers.…”

Intelligent Polymers, Fibers and Applications

“…Entering a new generation of enhanced widely used drug-delivery systems for humans has resulted in safety issues and research gaps requiring further investigation. Current research interests includes minimizing the degradation of pharmaceutically active ingredients during the in vivo transporting process [134] and optimizing the formulation methodology of nanoparticles with better release precision [135], as shown in Figure 7. For example, for site-specific drug delivery, Tiwari et al developed a tailorable fibrous platform [118] that can release rationally controlled drugs in an environment with pH 5.5, triggered by pH and near-infrared radiation (NIR).…”

“…Entering a new generation of enhanced widely used drug-delivery systems for humans has resulted in safety issues and research gaps requiring further investigation. Current research interests includes minimizing the degradation of pharmaceutically active ingredients during the in vivo transporting process [ 134 ] and optimizing the formulation methodology of nanoparticles with better release precision [ 135 ], as shown in Figure 7 .…”

Surface Modified Persistent Luminescence Probes for Biosensing and Bioimaging: A Review

“…With the increase of the concentration of miRNA‐21, TR‐FRET signals of FITC increased so that the detection of miRNA‐21 was realized (Figure 2B). Among the well‐studied biomacromolecules, aptamers (RNA or DNA oligonucleotides gained from SELEX) have drawn much attentions due to their high affinity and specificity to their targets, [ 27 ] and have been widely investigated in PLMs modification. Yan et al .…”