Polymeric Dendrimers as Nanocarrier Vectors for Neurotheranostics

Abstract

immune responses, activating cellular machinery causing cell stress, cytotoxicity, lack of selectivity, increasing the likelihood of replication competence, and the constrained structure of insert-size, which can limit their biological and medical applications. [2][3][4] By contrast, various forms of nonviral vectors are widely developed and applied in biomedical research because of their low immunogenicity, high biocompatibility, simplicity in structural pattern, ease of size adjustment, practicality in designing various active sites, and low cost of production. [5,6] The most widely studied nonviral vectors are liposomes, inorganic nanoparticles, polymers, and dendrimers. [7] Liposomes are small spherical vesicles from cholesterol and phospholipids characterized with the surface that can be modified using glycolipids or sialic acid. Yet, the unmodified forms of liposomes are structurally unstable and could easily be eliminated by means of body circulation. [8] In this situation, stable inorganic nanoparticles, such as calcium phosphate (Ca 3 (PO 4 ) 2 ), gold (Au), iron oxide (Fe 3 O 4 ), and lanthanide-based nanoparticles are widely used, mainly due to their good hydrophilicity and excellent biocompatibility. [9][10][11] Depending on their chemical core composition, these inorganic nanoparticles display different properties and efficiencies. Lately, inorganic nanoparticles have been developed as effective drug delivery systems and used in many diagnostic techniques. [12] In addition, polymers are widely used as nonviral vectors as well. [13][14][15] Polymers are biodegradable nanomaterials with stable and easily modifiable 3D structures. Their uncomplicated synthesis process allows for large-scale production and safe clinical use compared to inorganic nanoparticles. [16] Notably, dendrimers are hyperbranched polymers with a well-defined chemical structure: a core at the center occupied by array of convergent reactive chain-ends and surface that can easily be modified. [17] The chemistry of dendrimers was first described by Buhleier et al. in 1978. [18] In 1985, Tomalia et al. reported a newer kind of dendrimers based on the mixture of amines and amides, termed polyamidoamine (PAMAM) dendrimers. [19] Dendrimers are intermeshed synthetic organic macromolecules with 3D architecture composition and abundant terminal functional groups. They are well-defined monodispersity-sized materials with extraordinary membrane interaction properties Dendrimers are polymers with well-defined 3D branched structures that are vastly utilized in various neurotheranostics and biomedical applications, particularly as nanocarrier vectors. Imaging agents can be loaded into dendrimers to improve the accuracy of diagnostic imaging processes. Likewise, combining pharmaceutical agents and anticancer drugs with dendrimers can enhance their solubility, biocompatibility, and efficiency. Practically, by modifying ligands on the surface of dendrimers, effective therapeutic and diagnostic platforms can be constructed and implemented for target...

Functionalized Nanomaterials Capable of Crossing the Blood–Brain Barrier

“…Cationic NPs can be adsorbed to the plasma membrane surface of the EC through electrostatic interaction and then cross the BBB by adsorptive-mediated endocytosis, thus, exhibiting higher BBB permeability . However, compared to neutral and negatively charged NPs, cationic NPs showed higher cytotoxicity to ECs, and high macrophage uptake and clearance . Therefore, it is important to consider the benefit-to-risk ratio and adjust the surface charge of NPs to make them highly penetrable to the BBB with low cytotoxicity.…”

“…167 However, compared to neutral and negatively charged NPs, cationic NPs showed higher cytotoxicity to ECs, and high macrophage uptake and clearance. 168 Therefore, it is important to consider the benefit-to-risk ratio and adjust the surface charge of NPs to make them highly penetrable to the BBB with low cytotoxicity. fold.…”

“…Certainly, imaging modalities, like MR imaging, positron emission tomography imaging, and optical and photoacoustic imaging could also be employed to develop, boost, and expand such systems. For instance, upconversion nanoparticles (UCNPs) have a wide range of biological applications ,− and could be introduced for tracking and coupling polymer luminescent research. Future investigations could take advantage of the unique characteristics of the nanomaterials for combining diagnosis and therapies by creating and integrating various functional groups within one nanosystem to achieve highly sensitive and specific tasks.…”

Research Status of Dendrimer Micelles in Tumor Therapy for Drug Delivery

“…Due to the ability of drug delivery across the blood-brain barrier (BBB), dendritic polymers have drawn great interest in diagnosis and therapy for central nervous system disease. In the review of Li et al, [215] they mentioned that dendrimers across the BBB mainly through adsorption-mediated transcytosis and receptor-mediated transcytosis . Positively charged surfaces of dendrimers can conjugate onto the negatively charged plasma membrane of vascular endothelial cell, which facilitates them to path through the BBB via nonspecific endocytosis.…”

Branched Polymers: Synthesis and Application

“…Dendritic polymers have a controlled branching structure with tedious preparation process. 29,30 Dendritic polymers have a high degree of geometrical symmetry, cavities within the polymer, and a very high density of functional groups on the polymer surface. Their molecular volume, shape, and functional groups can be precisely controlled, while hyperbranched polymers can be produced by a one-step process, but the branching structure is imperfect and difficult to control.…”