Angiopep-pluronic F127-conjugated superparamagnetic iron oxide nanoparticles as nanotheranostic agents for BBB targeting

Chen, Guojing; Su, Ying-Jhen; Hsu, Chin; Lo, Yu-Lun; Huang, Shih-Jer; Ke, Jyun-Han; Kuo, Yung‐Chih; Wang, Li Fang

doi:10.1039/c4tb00543k

Cited by 22 publications

(13 citation statements)

References 38 publications

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“…As such, several targeting agents have been identified that facilitate ION transcytosis through specialized brain microvascular endothelial cells (BMECs), which grant their access to the brain parenchyma ( Table 2 ). The low-density lipoprotein receptor-related protein 1 (LRP1) is highly implicated in the transport of β-amyloid peptides, angiopep-2, and lactoferrin across BMECs and, therefore, has become a recurrent target for brain delivery [ 223 , 232 ]. As a member of the LDL receptor family, LRP1 is generally recognized by the CME machinery, although some studies have shown that caveolin-dependent endocytosis is also implicated [ 223 , 233 ].…”

Section: Enhancing Ion Internalizationmentioning

confidence: 99%

“…The low-density lipoprotein receptor-related protein 1 (LRP1) is highly implicated in the transport of β-amyloid peptides, angiopep-2, and lactoferrin across BMECs and, therefore, has become a recurrent target for brain delivery [ 223 , 232 ]. As a member of the LDL receptor family, LRP1 is generally recognized by the CME machinery, although some studies have shown that caveolin-dependent endocytosis is also implicated [ 223 , 233 ]. Xin and colleagues demonstrated that PEG-poly(e-caprolactone) coated IONs and further conjugated with angiopep-2 were easily loaded with paclitaxel (anti-cancer drug) to efficiently cross an in vitro BBB model.…”

Section: Enhancing Ion Internalizationmentioning

confidence: 99%

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Tailoring Iron Oxide Nanoparticles for Efficient Cellular Internalization and Endosomal Escape

et al. 2020

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Iron oxide nanoparticles (IONs) have been widely explored for biomedical applications due to their high biocompatibility, surface-coating versatility, and superparamagnetic properties. Upon exposure to an external magnetic field, IONs can be precisely directed to a region of interest and serve as exceptional delivery vehicles and cellular markers. However, the design of nanocarriers that achieve an efficient endocytic uptake, escape lysosomal degradation, and perform precise intracellular functions is still a challenge for their application in translational medicine. This review highlights several aspects that mediate the activation of the endosomal pathways, as well as the different properties that govern endosomal escape and nuclear transfection of magnetic IONs. In particular, we review a variety of ION surface modification alternatives that have emerged for facilitating their endocytic uptake and their timely escape from endosomes, with special emphasis on how these can be manipulated for the rational design of cell-penetrating vehicles. Moreover, additional modifications for enhancing nuclear transfection are also included in the design of therapeutic vehicles that must overcome this barrier. Understanding these mechanisms opens new perspectives in the strategic development of vehicles for cell tracking, cell imaging and the targeted intracellular delivery of drugs and gene therapy sequences and vectors.

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Section: Enhancing Ion Internalizationmentioning

confidence: 99%

Section: Enhancing Ion Internalizationmentioning

confidence: 99%

Tailoring Iron Oxide Nanoparticles for Efficient Cellular Internalization and Endosomal Escape

et al. 2020

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“…To this end, Ang-2 has been conjugated to numerous nanocarrier types in order to improve BBB crossing, including liposomes, tandem micelles, PEG-PCL, solid lipid nanoparticles, dendrigraft poly-l lysine, and poly-amidoamine dendrimers to deliver various active compounds (Coumarin, docetaxel, siRNA, etc.) [16][17][18][19].Poly(lactic-co-glycolic acid) (PLGA) is an FDA approved polymer that can self-assemble into nanoparticles, with selectable features including the size, shape, charge, and drug loading capacity as a function of the formulation parameters. Moreover, literature extensively reported its ability to encapsulate, protect, and deliver a wide range of bioactive compounds (small molecules, proteins, enzymes, etc.)…”

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confidence: 99%

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confidence: 99%

PLGA-PEG-ANG-2 Nanoparticles for Blood–Brain Barrier Crossing: Proof-of-Concept Study

et al. 2020

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The treatment of diseases that affect the central nervous system (CNS) represents a great research challenge due to the restriction imposed by the blood–brain barrier (BBB) to allow the passage of drugs into the brain. However, the use of modified nanomedicines engineered with different ligands that can be recognized by receptors expressed in the BBB offers a favorable alternative for this purpose. In this work, a BBB-penetrating peptide, angiopep-2 (Ang–2), was conjugated to poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles through pre- and post-formulation strategies. Then, their ability to cross the BBB was qualitatively assessed on an animal model. Proof-of-concept studies with fluorescent and confocal microscopy studies highlighted that the brain-targeted PLGA nanoparticles were able to cross the BBB and accumulated in neuronal cells, thus showing a promising brain drug delivery system.

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“…The BBB-penetrating peptide, angiopep-2 (ANG, sequence: TFFYGGRGKRNNFKTEEY), was conjugated onto the surface of Pluronic F127-modified water-dispersible poly(acrylic acid)-bound iron oxide (PF127-PAAIO). The ANG-PF127-PAAIO complex showed a better feasibility than PF127-PAAIO in U87 cells (negligible cell cytotoxicity, better cellular uptake, and higher T 2 -weighted image enhancement) [ 48 ]. Using an ex vivo BBB model, those authors showed that it was more permeable to ANG-PF127-PAAIO, and therefore this complex was more able to bypass the BBB.…”

Section: Spions Modified With Penetrating Peptides That Help To Pementioning

confidence: 99%

Magnetic Nanoparticles Cross the Blood-Brain Barrier: When Physics Rises to a Challenge

et al. 2015

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Abstract:The blood-brain barrier is a physical and physiological barrier that protects the brain from toxic substances within the bloodstream and helps maintain brain homeostasis. It also represents the main obstacle in the treatment of many diseases of the central nervous system. Among the different approaches employed to overcome this barrier, the use of nanoparticles as a tool to enhance delivery of therapeutic molecules to the brain is particularly promising. There is special interest in the use of magnetic nanoparticles, as their physical characteristics endow them with additional potentially useful properties. Following systemic administration, a magnetic field applied externally can mediate the capacity of magnetic nanoparticles to permeate the blood-brain barrier. Meanwhile, thermal energy released by magnetic nanoparticles under the influence of radiofrequency radiation can modulate blood-brain barrier integrity, increasing its permeability. In this review, we present the strategies that use magnetic nanoparticles, specifically iron oxide nanoparticles, to enhance drug delivery to the brain.

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Angiopep-pluronic F127-conjugated superparamagnetic iron oxide nanoparticles as nanotheranostic agents for BBB targeting

Cited by 22 publications

References 38 publications

Tailoring Iron Oxide Nanoparticles for Efficient Cellular Internalization and Endosomal Escape

Tailoring Iron Oxide Nanoparticles for Efficient Cellular Internalization and Endosomal Escape

PLGA-PEG-ANG-2 Nanoparticles for Blood–Brain Barrier Crossing: Proof-of-Concept Study

Magnetic Nanoparticles Cross the Blood-Brain Barrier: When Physics Rises to a Challenge

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