Application progress of RVG peptides to facilitate the delivery of therapeutic agents into the central nervous system

Wang, Qinghua; Shang, Cheng; Qin, Fang; Fu, Ailing; Fu, Chen

doi:10.1039/d1ra00550b

Cited by 39 publications

(27 citation statements)

References 106 publications

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“…Neurotropic viruses can cross the BBB and invade the brain parenchyma, which prompted the investigation of viruses or viral components as transporters for the brain delivery of therapeutics. For instance, peptides derived from rabies virus glycoprotein (RVG) exhibit efficient penetration through the BBB and target neurons [ 72 ]. Although the exact BBB crossing mechanism is unknown, it is expected to occur via neuronal acetylcholine receptor-mediated RMT [ 72 ].…”

Section: Current Strategies For Delivering Therapeutics Across the Bbbmentioning

confidence: 99%

“…For instance, peptides derived from rabies virus glycoprotein (RVG) exhibit efficient penetration through the BBB and target neurons [ 72 ]. Although the exact BBB crossing mechanism is unknown, it is expected to occur via neuronal acetylcholine receptor-mediated RMT [ 72 ]. RVG has been utilized for the delivery of various nanoparticles through the BBB, including liposomes [ 73 ], layered double hydroxide [ 74 ], porous silicon nanoparticles [ 75 ], and exosomes [ 76 ].…”

Section: Current Strategies For Delivering Therapeutics Across the Bbbmentioning

confidence: 99%

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Strategies for Targeted Delivery of Exosomes to the Brain: Advantages and Challenges

Choi¹,

Choi²,

Kim³

et al. 2022

Pharmaceutics

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Delivering therapeutics to the central nervous system (CNS) is difficult because of the blood–brain barrier (BBB). Therapeutic delivery across the tight junctions of the BBB can be achieved through various endogenous transportation mechanisms. Receptor-mediated transcytosis (RMT) is one of the most widely investigated and used methods. Drugs can hijack RMT by expressing specific ligands that bind to receptors mediating transcytosis, such as the transferrin receptor (TfR), low-density lipoprotein receptor (LDLR), and insulin receptor (INSR). Cell-penetrating peptides and viral components originating from neurotropic viruses can also be utilized for the efficient BBB crossing of therapeutics. Exosomes, or small extracellular vesicles, have gained attention as natural nanoparticles for treating CNS diseases, owing to their potential for natural BBB crossing and broad surface engineering capability. RMT-mediated transport of exosomes expressing ligands such as LDLR-targeting apolipoprotein B has shown promising results. Although surface-modified exosomes possessing brain targetability have shown enhanced CNS delivery in preclinical studies, the successful development of clinically approved exosome therapeutics for CNS diseases requires the establishment of quantitative and qualitative methods for monitoring exosomal delivery to the brain parenchyma in vivo as well as elucidation of the mechanisms underlying the BBB crossing of surface-modified exosomes.

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Section: Current Strategies For Delivering Therapeutics Across the Bbbmentioning

confidence: 99%

Section: Current Strategies For Delivering Therapeutics Across the Bbbmentioning

confidence: 99%

Strategies for Targeted Delivery of Exosomes to the Brain: Advantages and Challenges

Choi¹,

Choi²,

Kim³

et al. 2022

Pharmaceutics

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“…By introducing targeting ligands, dendrimers are functional to amplify the permeability of BBB and achieve targeted delivery for the CNS diseases diagnosis and treatment. [ 195 ]…”

Section: Biomedical Applications Of Dendrimers In the Cns Disease Tre...mentioning

confidence: 99%

“…By introducing targeting ligands, dendrimers are functional to amplify the permeability of BBB and achieve targeted delivery for the CNS diseases diagnosis and treatment. [195] In recent years, several PAMAM dendrimers as nanocarriers for imaging agents have been reported for applicability in CNS diseases diagnosis. [196] The G4 mixed-surface PAMAM dendrimer with low toxicity was designed and synthesized by Munro et al [197] Most of the amine groups (90%) on the exterior of PAMAM dendrimers are replaced by hydroxyl groups, and the reserved amine (10%) is readily fluorescently tagged to provide imaging.…”

Section: Biomedical Applications Of Dendrimers In the Cns Disease Tre...mentioning

confidence: 99%

Polymeric Dendrimers as Nanocarrier Vectors for Neurotheranostics

Zha

Liu

et al. 2022

Small

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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...

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“…Hence, innovative strategies utilizing nanoparticles (NPs), graphene, and peptide modified carriers are proposed as advanced methods that may increase drug delivery across the BBB (Barani et al 2021;Wang et al 2021), resulting in improved treatment of amoebic brain infections. Encouragingly, recent studies have depicted nanotechnology in the improvement of drug efficacy against amoebae (Anwar et al 2019a, b, c, d;Mungroo et al 2020;Rajendran et al 2019;Walvekar et al 2020).…”

Section: Introductionmentioning

confidence: 99%

Nanovehicles in the improved treatment of infections due to brain-eating amoebae

et al. 2021

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Pathogenic free-living amoebae are known to cause fatal central nervous system infections with extremely high mortality rates. High selectivity of the blood-brain barrier hampers delivery of drugs and untargeted delivery of drugs can cause severe side effects. Nanovehicles can be used for targeted drug delivery across the blood-brain barrier. Inorganic nanoparticles have been explored as carriers for various biomedical applications and can be modified with various ligands for efficient targeting and cell selectivity while lipid-based nanoparticles have been extensively used in the development of both precision and colloidal nanovehicles. Nanomicelles and polymeric nanoparticles can also serve as nanocarriers and may be modified so that responsiveness of the nanoparticles and release of the loads are linked to specific stimuli. These nanoparticles are discussed here in the context of the treatment of central nervous system infections due to pathogenic amoebae. It is anticipated that these novel strategies can be utilized in tandem with novel drug leads currently in the pipeline and yield in the development of much needed treatments against these devastating parasites.

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Application progress of RVG peptides to facilitate the delivery of therapeutic agents into the central nervous system

Abstract: Rabies virus glycoprotein (RVG) peptides have been developed to deliver drugs for CNS diseases. In the present review, RVG-mediated drug delivery systems are summarised, which can deliver almost all small molecules and macromolecule agents.

Cited by 39 publications

References 106 publications

Strategies for Targeted Delivery of Exosomes to the Brain: Advantages and Challenges

Strategies for Targeted Delivery of Exosomes to the Brain: Advantages and Challenges

Polymeric Dendrimers as Nanocarrier Vectors for Neurotheranostics

Nanovehicles in the improved treatment of infections due to brain-eating amoebae

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