Multifunctional exosome-mimetics for targeted anti-glioblastoma therapy by manipulating protein corona

AbstractTargeted drug delivery to the glioblastoma (GBM) overcoming blood–brain barrier (BBB) has been challenging. Exosomes are promising vehicles for brain tumor drug delivery, but the production and purification hinder its application for nanomedicine. Besides, the formation of protein corona (PC) may affect the behaviour of nanocarriers. Here, multifunctional exosomes-mimetics (EM) are developed and decorated with angiopep-2 (Ang) for enhancing GBM drug delivery by manipulating PC. Docetaxel (DTX)-loaded EM with Ang modification (DTX@Ang-EM) show less absorption of serum proteins and phagocytosis by macrophages. Ang-EM show enhanced BBB penetration ability and targeting ability to the GBM. Ang-EM-mediated delivery increase the concentration of DTX in the tumor area. The multifunctional DTX@Ang-EM exhibits significant inhibition effects on orthotopic GBM growth with reduced side effects of the chemotherapeutic. Findings from this study indicate that the developed DTX@Ang-EM provide a new strategy for targeted brain drug delivery and GBM therapy. Graphical abstract

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Combinatorial targeting polymeric micelles for anti-tumor drug delivery

Journal of Materials Chemistry B ◽

10.1039/c5tb00347d ◽

2015 ◽

Vol 3 (19) ◽

pp. 4043-4051 ◽

Cited By ~ 23

Author(s):

Saina Yang ◽

Feiyan Zhu ◽

Qian Wang ◽

Fuxin Liang ◽

Xiaozhong Qu ◽

...

Keyword(s):

Drug Delivery ◽

Cancer Cells ◽

Polymeric Micelles ◽

Tumor Ph ◽

Tumor Drug Delivery ◽

Targeting Ability

Polymeric micelles with combinatorial targeting ability for cancer cells was achieved by co-assembly of cRGD-PEO-b-PCL and tumor pHesensitive PEG-DOX.

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Emerging Nano-Carrier Strategies for Brain Tumor Drug Delivery and Considerations for Clinical Translation

Pharmaceutics ◽

10.3390/pharmaceutics13081193 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1193

Author(s):

David J. Lundy ◽

Helen Nguyễn ◽

Patrick C. H. Hsieh

Keyword(s):

Drug Delivery ◽

Brain Tumor ◽

Brain Tumors ◽

Clinical Use ◽

Brain Disorders ◽

Regulatory Issues ◽

Chemotherapy Drugs ◽

Brain Drug Delivery ◽

Clinical Models ◽

Tumor Drug Delivery

Treatment of brain tumors is challenging since the blood–brain tumor barrier prevents chemotherapy drugs from reaching the tumor site in sufficient concentrations. Nanomedicines have great potential for therapy of brain disorders but are still uncommon in clinical use despite decades of research and development. Here, we provide an update on nano-carrier strategies for improving brain drug delivery for treatment of brain tumors, focusing on liposomes, extracellular vesicles and biomimetic strategies as the most clinically feasible strategies. Finally, we describe the obstacles in translation of these technologies including pre-clinical models, analytical methods and regulatory issues.

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Therapeutic Efficacy of 5-Fluorouracil Prodrugs Using Endogenous Serum Proteins as Drug Carriers: A New Strategy in Drug Delivery System.

Biological and Pharmaceutical Bulletin ◽

10.1248/bpb.18.181 ◽

1995 ◽

Vol 18 (1) ◽

pp. 181-184 ◽

Cited By ~ 6

Author(s):

Naoto OKU ◽

Shinji YAMASHITA ◽

Naoko SAKURAGI ◽

Kanako DOI ◽

Shoji OKADA ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Therapeutic Efficacy ◽

Serum Proteins ◽

Drug Carriers ◽

New Strategy

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Enhancing Tumor Drug Delivery by Laser-Activated Vascular Barrier Disruption

10.21236/ada479423 ◽

2007 ◽

Author(s):

Bin Chen ◽

Chong He

Keyword(s):

Drug Delivery ◽

Barrier Disruption ◽

Tumor Drug Delivery

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Enhancing Tumor Drug Delivery by Laser-Activated Vascular Barrier Disruption

10.21236/ada495307 ◽

2008 ◽

Author(s):

Bin Chen ◽

Chong He

Keyword(s):

Drug Delivery ◽

Barrier Disruption ◽

Tumor Drug Delivery

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Nose-to-Brain Drug Delivery by Nanoparticles in the Treatment of Neurological Disorders

Current Medicinal Chemistry ◽

10.2174/0929867321666140716103130 ◽

2014 ◽

Vol 21 (37) ◽

pp. 4247-4256 ◽

Cited By ~ 31

Author(s):

Wei-Yi Ong ◽

Suku-Maran Shalini ◽

Luca Costantino

Keyword(s):

Drug Delivery ◽

Neurological Disorders ◽

Brain Drug Delivery

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Brain Drug Delivery: Overcoming the Blood-brain Barrier to Treat Tauopathies

Current Pharmaceutical Design ◽

10.2174/1381612826666200316130128 ◽

2020 ◽

Vol 26 (13) ◽

pp. 1448-1465 ◽

Cited By ~ 1

Author(s):

Jozef Hanes ◽

Eva Dobakova ◽

Petra Majerova

Keyword(s):

Drug Delivery ◽

Blood Brain Barrier ◽

Neurodegenerative Disorders ◽

Brain Barrier ◽

Neuronal Function ◽

Brain Drug Delivery ◽

Naturally Occurring ◽

Blood Brain ◽

Traditional Approaches ◽

The Brain

Tauopathies are neurodegenerative disorders characterized by the deposition of abnormal tau protein in the brain. The application of potentially effective therapeutics for their successful treatment is hampered by the presence of a naturally occurring brain protection layer called the blood-brain barrier (BBB). BBB represents one of the biggest challenges in the development of therapeutics for central nervous system (CNS) disorders, where sufficient BBB penetration is inevitable. BBB is a heavily restricting barrier regulating the movement of molecules, ions, and cells between the blood and the CNS to secure proper neuronal function and protect the CNS from dangerous substances and processes. Yet, these natural functions possessed by BBB represent a great hurdle for brain drug delivery. This review is concentrated on summarizing the available methods and approaches for effective therapeutics’ delivery through the BBB to treat neurodegenerative disorders with a focus on tauopathies. It describes the traditional approaches but also new nanotechnology strategies emerging with advanced medical techniques. Their limitations and benefits are discussed.

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Polymeric Nanoparticles for Brain Drug Delivery - A Review

Current Drug Metabolism ◽

10.2174/1389200221666200508074348 ◽

2020 ◽

Vol 21 (9) ◽

pp. 649-660

Author(s):

Subashini Raman ◽

Syed Mahmood ◽

Ayah R. Hilles ◽

Md Noushad Javed ◽

Motia Azmana ◽

...

Keyword(s):

Drug Delivery ◽

Surface Modification ◽

Polymeric Nanoparticles ◽

Drug Loading ◽

Preparation Methods ◽

Brain Drug Delivery ◽

Polymeric Nanoparticle ◽

Relationship Of ◽

The Relationship ◽

The Brain

Background: Blood-brain barrier (BBB) plays a most hindering role in drug delivery to the brain. Recent research comes out with the nanoparticles approach, is continuously working towards improving the delivery to the brain. Currently, polymeric nanoparticle is extensively involved in many therapies for spatial and temporal targeted areas delivery. Methods: We did a non-systematic review, and the literature was searched in Google, Science Direct and PubMed. An overview is provided for the formulation of polymeric nanoparticles using different methods, effect of surface modification on the nanoparticle properties with types of polymeric nanoparticles and preparation methods. An account of different nanomedicine employed with therapeutic agent to cross the BBB alone with biodistribution of the drugs. Results: We found that various types of polymeric nanoparticle systems are available and they prosper in delivering the therapeutic amount of the drug to the targeted area. The effect of physicochemical properties on nanoformulation includes change in their size, shape, elasticity, surface charge and hydrophobicity. Surface modification of polymers or nanocarriers is also vital in the formulation of nanoparticles to enhance targeting efficiency to the brain. Conclusion: More standardized methods for the preparation of nanoparticles and to assess the relationship of surface modification on drug delivery. While the preparation and its output like drug loading, particle size, and charge, permeation is always conflicted, so it requires more attention for the acceptance of nanoparticles for brain delivery.

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