Enhanced BBB permeability of osmotically active poly(mannitol-co-PEI) modified with rabies virus glycoprotein via selective stimulation of caveolar endocytosis for RNAi therapeutics in Alzheimer's disease

Park, Tae‐Eun; Singh, Bijay; Li, Huishan; Lee, Jun-Yeong; Kang, Sang-Kee; Choi, Yun‐Jaie; Cho, Chong‐Su

doi:10.1016/j.biomaterials.2014.10.068

Cited by 119 publications

(68 citation statements)

References 43 publications

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“…For the present studies, targeting ligands were selected based on their potential for BBB uptake in prior reports (15, 16, 42–45, 47, 48, 64). In our work, PLGA-DSPE-PEG NPs conjugated with RVG or the control peptide RVMAT did not lead to increased accumulation of NPs in the brain.…”

Section: Discussionmentioning

confidence: 99%

“…Among transporters, receptors that are involved in receptor-mediated endocytosis, and capable of trafficking molecules into and through the cell (37)—such as receptors for insulin (38), transferrin (33), and low-density lipoprotein (39)—are of particular interest. Rabies virus glycoprotein (RVG), a 29 amino acid cell-penetrating peptide derived from an active targeting region of the rabies virus, has been found to specifically bind to the alpha subunit of the nicotinic acetylcholine receptor resulting in receptor-mediated transcytosis (40–42) and has been shown to be an effective targeting agent for certain particulates (42–45). TGN, a 12 amino acid peptide, was discovered through in vivo phage display in a mouse model.…”

Section: Introductionmentioning

confidence: 99%

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Systemic delivery of blood–brain barrier-targeted polymeric nanoparticles enhances delivery to brain tissue

Saucier-Sawyer¹,

Deng²,

Seo³

et al. 2015

Journal of Drug Targeting

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Delivery of therapeutic agents to the central nervous system is a significant challenge, hindering progress in the treatment of diseases such as glioblastoma. Due to the presence of the blood-brain barrier (BBB), therapeutic agents do not readily transverse the brain endothelium to enter the parenchyma. Previous reports suggest that surface modification of polymer nanoparticles can improve their ability to cross the BBB, but it is unclear whether the observed enhancements in transport are large enough to enhance therapy. In this study, we synthesized two degradable polymer nanoparticle systems surface-modified with ligands previously suggested to improve BBB transport, and tested their ability to cross the BBB after intravenous injection in mice. All nanoparticle preparations were able to cross the BBB, although generally in low amounts (<0.5% of the injected dose), which was consistent with prior reports. One nanoparticle produced significantly higher brain uptake (~0.8% of the injected dose): a block copolymer of polylactic acid and hyperbranched polyglycerol, surface modified with adenosine (PLA-HPG-Ad). PLA-HPG-Ad nanoparticles provided controlled release of camptothecin, killing U87 glioma cells in culture. When administered intravenously in mice with intracranial U87 tumors, they failed to increase survival. These results suggest that enhancing nanoparticle transport across the BBB does not necessarily yield proportional pharmacological effects.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Systemic delivery of blood–brain barrier-targeted polymeric nanoparticles enhances delivery to brain tissue

Saucier-Sawyer¹,

Deng²,

Seo³

et al. 2015

Journal of Drug Targeting

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“…Targeting strategies could enhance the recognition and cellular uptake of MSNs in cancer cells that can taper the therapeutic doses and unwanted off‐target side effects. Generally, conjugation has been carried out on the surface of MSNs using targeted molecules such as RGD (arginine–glycine–aspartic acid), transferrin, folic acid, and mannose …”

Section: Applications Of Msnsmentioning

confidence: 99%

Multidisciplinary Role of Mesoporous Silica Nanoparticles in Brain Regeneration and Cancers: From Crossing the Blood–Brain Barrier to Treatment

Mendiratta

Hussein

Nasser

et al. 2019

Part & Part Syst Charact

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that by 2040, neurodegenerative diseases will surpass cancer as the second reason of death after cardiovascular diseases in such aged populations. [1,2] As per a 2017 report, neurological diseases cost the United States of America about $800 billion annually and this number is expected to increase even further over the coming years as the percentage of aged citizens increases. [3] Unlike most other major diseases, the pace of drug development and delivery in case of neurodegenerative diseases has been stationary, partially due to lack of biomarkers that can diagnose such diseases long before the neurological symptoms arise and the challenges associated with identification of targets for drugs that can terminate or minimize neurodegeneration. Most importantly, delivering new cerebral therapeutic agents is impeded by the extensive and robust blood-brain barrier (BBB) which prevents the vast majority of drugs from crossing to the brain after systemic administration. During brain infections, intracerebral hemorrhage, or in neurodegenerative disorders, the BBB is altered in such a way that it allows easy access of inflammatory inducing molecules that may cause adverse neuronal damage. [4] Given the importance of early diagnosis and treatment of neurodegenerative diseases, new drug delivery technologies have appeared in the last decade.As shown in Scheme 1, unique nanomaterials have been reported and several nanosized drug delivery systems including liposomes, dendrimers, carbon nanotubes (CNTs), inorganic and hybrid nanoparticles, and polymeric micelles have gained attention and have been tested for targeted drug delivery not only for neurodegenerative diseases but also for several other ailments. [5][6][7][8][9][10] The discovery of MCM-41 was recognized as a major breakthrough in materials science and since then mesoporous silica nanoparticles (MSNs), thanks to their superior physiochemical properties such as large porosity, high surface areas, low toxicity, controllable sizes, and wide range of morphologies compared to conventional nanoparticles (NPs) have emerged as favorable tools in biomedical applications as nanocarriers for encapsulation and delivery of therapeutic medicines. [11][12][13][14] Designing biocompatible MSNs and their multifunctional derivatives for drug transport as well as theranostics is one of the hottest areas of research in the field of nanobiotechnology and nanomedicine. [15][16][17][18][19] High loading capacity, acceptable biocompatibility, and limitless possibilities of surface functionalization for specific cellular recognition Mesoporous silica nanoparticles (MSNs) have gained wide attention for their role in biomedicine and as drug delivery vehicles. Their structural tunability, high surface area, and easy functionalization impart significant advantages over conventional materials. In this Review, recent advances in the synthesis, drug delivery, and therapeutic roles of MSNs in the treatment of various neurodegenerative and neuroinflammatory diseases are presented. The intention is to...

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“…Another major obstacle is how to make the drugs pass through the blood-brain barrier with high efficiency. While ultrasonic waves (Burgess et al, 2015) and some chemicals such as mannitol (Park et al, 2015) have been reported to open the blood-brain barrier, it has yet to be tested whether they are safe for in vivo chemical reprogramming. Even if drugs can reach the brain or spinal cord, they will need to act more specifically on glial cells, and ideally on reactive glial cells, without serious side effects on existing neurons or other cells.…”

Section: Challenges For In Vivo Reprogrammingmentioning

confidence: 99%

In Vivo Reprogramming for CNS Repair: Regenerating Neurons from Endogenous Glial Cells

Chen

2016

Neuron

143

106

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Neuroregeneration in the central nervous system (CNS) has proven to be difficult despite decades of research. The old dogma that CNS neurons cannot be regenerated in the adult mammalian brain has been overturned; however, endogenous adult neurogenesis appears to be insufficient for brain repair. Stem cell therapy once held promise for generating large quantities of neurons in the CNS, but immunorejection and long-term functional integration remain major hurdles. In this perspective, we discuss the use of in vivo reprogramming as an emerging technology to regenerate functional neurons from endogenous glial cells inside the brain and spinal cord. Besides the CNS, in vivo reprogramming has been demonstrated successfully in the pancreas, heart and liver, and may be adopted in other organs. Although challenges remain for translating this technology into clinical therapies, we anticipate that in vivo reprogramming may revolutionize regenerative medicine by using a patient’s own internal cells for tissue repair.

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Enhanced BBB permeability of osmotically active poly(mannitol-co-PEI) modified with rabies virus glycoprotein via selective stimulation of caveolar endocytosis for RNAi therapeutics in Alzheimer's disease

Cited by 119 publications

References 43 publications

Systemic delivery of blood–brain barrier-targeted polymeric nanoparticles enhances delivery to brain tissue

Systemic delivery of blood–brain barrier-targeted polymeric nanoparticles enhances delivery to brain tissue

Multidisciplinary Role of Mesoporous Silica Nanoparticles in Brain Regeneration and Cancers: From Crossing the Blood–Brain Barrier to Treatment

In Vivo Reprogramming for CNS Repair: Regenerating Neurons from Endogenous Glial Cells

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