Exosomes for mRNA delivery: a novel biotherapeutic strategy with hurdles and hope

AbstractOver the past decade, therapeutic messenger RNAs (mRNAs) have emerged as a highly promising new class of drugs for protein replacement therapies. Due to the recent developments, the incorporation of modified nucleotides in synthetic mRNAs can lead to maximizing protein expression and reducing adverse immunogenicity. Despite these stunning improvements, mRNA therapy is limited by the need for the development of safe and efficient carriers to protect the mRNA integrity for in vivo applications. Recently, leading candidates for in vivo drug delivery vehicles are cell-derived exosomes, which have fewer immunogenic responses. In the current study, the key hurdles facing mRNA-based therapeutics, with an emphasis on recent strategies to overcoming its immunogenicity and instability, were highlighted. Then the immunogenicity and toxicity of exosomes derived from various cell sources were mentioned in detail. Finally, an overview of the recent strategies in using exosomes for mRNA delivery in the treatment of multiple diseases was stated.

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From structures to functions: insights into exosomes as promising drug delivery vehicles

Biomaterials Science ◽

10.1039/c5bm00583c ◽

2016 ◽

Vol 4 (6) ◽

pp. 910-921 ◽

Cited By ~ 49

Author(s):

Jinghua Ren ◽

Wenshan He ◽

Lifen Zheng ◽

Hongwei Duan

Keyword(s):

Drug Delivery ◽

Drug Delivery Vehicles ◽

New Class ◽

Recent Developments ◽

Delivery Vehicles

This review summarizes recent developments in exploiting cell-derived exosomes as a new class of nanoscale drug delivery carriers.

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Novel Phospholipid-Based Labrasol Nanomicelles Loaded Flavonoids for Oral Delivery with Enhanced Penetration and Anti-Brain Tumor Efficiency

Current Drug Delivery ◽

10.2174/1567201817666200210120950 ◽

2020 ◽

Vol 17 (3) ◽

pp. 229-245

Author(s):

Gang Wang ◽

Junjie Wang ◽

Rui Guan

Keyword(s):

Drug Delivery ◽

Brain Tumor ◽

Oral Delivery ◽

Safe Delivery ◽

Drug Delivery Vehicles ◽

Therapeutic Benefits ◽

Delivery Vehicles ◽

The Brain

Background: Owing to the rich anticancer properties of flavonoids, there is a need for their incorporation into drug delivery vehicles like nanomicelles for safe delivery of the drug into the brain tumor microenvironment. Objective: This study, therefore, aimed to prepare the phospholipid-based Labrasol/Pluronic F68 modified nano micelles loaded with flavonoids (Nano-flavonoids) for the delivery of the drug to the target brain tumor. Methods: Myricetin, quercetin and fisetin were selected as the initial drugs to evaluate the biodistribution and acute toxicity of the drug delivery vehicles in rats with implanted C6 glioma tumors after oral administration, while the uptake, retention, release in human intestinal Caco-2 cells and the effect on the brain endothelial barrier were investigated in Human Brain Microvascular Endothelial Cells (HBMECs). Results: The results demonstrated that nano-flavonoids loaded with myricetin showed more evenly distributed targeting tissues and enhanced anti-tumor efficiency in vivo without significant cytotoxicity to Caco-2 cells and alteration in the Trans Epithelial Electric Resistance (TEER). There was no pathological evidence of renal, hepatic or other organs dysfunction after the administration of nanoflavonoids, which showed no significant influence on cytotoxicity to Caco-2 cells. Conclusion: In conclusion, Labrasol/F68-NMs loaded with MYR and quercetin could enhance antiglioma effect in vitro and in vivo, which may be better tools for medical therapy, while the pharmacokinetics and pharmacodynamics of nano-flavonoids may ensure optimal therapeutic benefits.

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Biodistribution and Pharmacokinectics of Liposomes and Exosomes in a Mouse Model of Sepsis

Pharmaceutics ◽

10.3390/pharmaceutics13030427 ◽

2021 ◽

Vol 13 (3) ◽

pp. 427

Author(s):

Amin Mirzaaghasi ◽

Yunho Han ◽

So-Hee Ahn ◽

Chulhee Choi ◽

Ji-Ho Park

Keyword(s):

Drug Delivery ◽

Therapeutic Potential ◽

Hek293t Cell ◽

Biological Properties ◽

Context Analysis ◽

Drug Delivery Vehicles ◽

Delivery Vehicles ◽

Diseased State ◽

Sepsis And Septic Shock

Exosomes have attracted considerable attention as drug delivery vehicles because their biological properties can be utilized for selective delivery of therapeutic cargoes to disease sites. In this context, analysis of the in vivo behaviors of exosomes in a diseased state is required to maximize their therapeutic potential as drug delivery vehicles. In this study, we investigated biodistribution and pharmacokinetics of HEK293T cell-derived exosomes and PEGylated liposomes, their synthetic counterparts, into healthy and sepsis mice. We found that biodistribution and pharmacokinetics of exosomes were significantly affected by pathophysiological conditions of sepsis compared to those of liposomes. In the sepsis mice, a substantial number of exosomes were found in the lung after intravenous injection, and their prolonged blood residence was observed due to the liver dysfunction. However, liposomes did not show such sepsis-specific effects significantly. These results demonstrate that exosome-based therapeutics can be developed to manage sepsis and septic shock by virtue of their sepsis-specific in vivo behaviors.

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Advances in Molecularly Imprinted Polymers as Drug Delivery Systems

Molecules ◽

10.3390/molecules26123589 ◽

2021 ◽

Vol 26 (12) ◽

pp. 3589

Author(s):

Rui Liu ◽

Alessandro Poma

Keyword(s):

Drug Delivery ◽

Molecularly Imprinted Polymers ◽

Drug Loading ◽

Stimuli Responsive ◽

Molecularly Imprinted ◽

Imprinted Polymers ◽

Drug Delivery Vehicles ◽

The Past ◽

Drug Molecules ◽

Delivery Vehicles

Despite the tremendous efforts made in the past decades, severe side/toxic effects and poor bioavailability still represent the main challenges that hinder the clinical translation of drug molecules. This has turned the attention of investigators towards drug delivery vehicles that provide a localized and controlled drug delivery. Molecularly imprinted polymers (MIPs) as novel and versatile drug delivery vehicles have been widely studied in recent years due to the advantages of selective recognition, enhanced drug loading, sustained release, and robustness in harsh conditions. This review highlights the design and development of strategies undertaken for MIPs used as drug delivery vehicles involving different drug delivery mechanisms, such as rate-programmed, stimuli-responsive and active targeting, published during the course of the past five years.

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Cytochrome c end-capped mesoporous silica nanoparticles as redox-responsive drug delivery vehicles for liver tumor-targeted triplex therapy in vitro and in vivo

Journal of Controlled Release ◽

10.1016/j.jconrel.2014.06.037 ◽

2014 ◽

Vol 192 ◽

pp. 192-201 ◽

Cited By ~ 98

Author(s):

Beilu Zhang ◽

Zhong Luo ◽

Junjie Liu ◽

Xingwei Ding ◽

Jinghua Li ◽

...

Keyword(s):

Drug Delivery ◽

Cytochrome C ◽

Mesoporous Silica ◽

Liver Tumor ◽

Mesoporous Silica Nanoparticles ◽

Drug Delivery Vehicles ◽

Redox Responsive ◽

Delivery Vehicles

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Physicochemical characterization, toxicity and in vivo biodistribution studies of a discoidal, lipid-based drug delivery vehicle: Lipodisq nanoparticles containing doxorubicin

10.1101/2020.06.18.159087 ◽

2020 ◽

Author(s):

Maria Lyngaas Torgersen ◽

Peter J. Judge ◽

Juan F. Bada Juarez ◽

Abhilash D. Pandya ◽

Markus Fusser ◽

...

Keyword(s):

Drug Delivery ◽

Physicochemical Characterization ◽

Phospholipid Bilayer ◽

Drug Delivery Vehicles ◽

Carboxylate Groups ◽

Biodistribution Studies ◽

Aqueous Environments ◽

Delivery Vehicles ◽

Doxorubicin Release

AbstractMany promising pharmaceutically active compounds have low solubility in aqueous environments and their encapsulation into efficient drug delivery vehicles is crucial to increase their bioavailability. Lipodisq nanoparticles are approximately 10 nm in diameter and consist of a circular phospholipid bilayer, stabilized by an annulus of SMA (a hydrolysed copolymer of styrene and maleic anhydride). SMA is used extensively in structural biology to extract and stabilize integral membrane proteins for biophysical studies. Here, we assess the potential of these nanoparticles as drug delivery vehicles, determining their cytotoxicity and the in vivo excretion pathways of their polymer and lipid components. Doxorubicin-loaded Lipodisqs were cytotoxic across a panel of cancer cell lines, whereas nanoparticles without the drug had no effect on cell proliferation. Intracellular doxorubicin release from Lipodisqs in HeLa cells occurred in the low-pH environment of the endolysosomal system, consistent with the breakdown of the discoidal structure as the carboxylate groups of the SMA polymer become protonated. Biodistribution studies in mice showed that, unlike other nanoparticles injected intravenously, most of the Lipodisq components were recovered in the colon, consistent with rapid uptake by hepatocytes and excretion into bile. These data suggest that Lipodisqs have the potential to act as delivery vehicles for drugs and contrast agents.

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Can nanotechnology potentiate photodynamic therapy?

Nanotechnology Reviews ◽

10.1515/ntrev-2011-0005 ◽

2012 ◽

Vol 1 (2) ◽

pp. 111-146 ◽

Cited By ~ 84

Author(s):

Ying-Ying Huang ◽

Sulbha K. Sharma ◽

Tianhong Dai ◽

Hoon Chung ◽

Anastasia Yaroslavsky ◽

...

Keyword(s):

Drug Delivery ◽

Photodynamic Therapy ◽

Plasmonic Enhancement ◽

Gold And Silver Nanoparticles ◽

Drug Delivery Vehicles ◽

Two Photon ◽

Photon Excitation ◽

Poorly Soluble ◽

Delivery Vehicles

AbstractPhotodynamic therapy (PDT) uses the combination of nontoxic dyes and harmless visible light to produce reactive oxygen species that can kill cancer cells and infectious microorganisms. Due to the tendency of most photosensitizers (PS) to be poorly soluble and to form nonphotoactive aggregates, drug-delivery vehicles have become of high importance. The nanotechnology revolution has provided many examples of nanoscale drug-delivery platforms that have been applied to PDT. These include liposomes, lipoplexes, nanoemulsions, micelles, polymer nanoparticles (degradable and nondegradable), and silica nanoparticles. In some cases (fullerenes and quantum dots), the actual nanoparticle itself is the PS. Targeting ligands such as antibodies and peptides can be used to increase specificity. Gold and silver nanoparticles can provide plasmonic enhancement of PDT. Two-photon excitation or optical upconversion can be used instead of one-photon excitation to increase tissue penetration at longer wavelengths. Finally, after sections on in vivo studies and nanotoxicology, we attempt to answer the title question, “can nanotechnology potentiate PDT?”

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An Update on in Vivo Imaging of Extracellular Vesicles as Drug Delivery Vehicles

Frontiers in Pharmacology ◽

10.3389/fphar.2018.00169 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 40

Author(s):

Prakash Gangadaran ◽

Chae Moon Hong ◽

Byeong-Cheol Ahn

Keyword(s):

Drug Delivery ◽

Extracellular Vesicles ◽

In Vivo Imaging ◽

Drug Delivery Vehicles ◽

Delivery Vehicles

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Physicochemical Characterization, Toxicity and In Vivo Biodistribution Studies of a Discoidal, Lipid-Based Drug Delivery Vehicle: Lipodisq Nanoparticles Containing Doxorubicin

Journal of Biomedical Nanotechnology ◽

10.1166/jbn.2020.2911 ◽

2020 ◽

Vol 16 (4) ◽

pp. 419-431

Author(s):

Maria Lyngaas Torgersen ◽

Peter J. Judge ◽

Juan F. Bada Juarez ◽

Abhilash D. Pandya ◽

Markus Fusser ◽

...

Keyword(s):

Drug Delivery ◽

Physicochemical Characterization ◽

Phospholipid Bilayer ◽

Drug Delivery Vehicles ◽

Carboxylate Groups ◽

Biodistribution Studies ◽

Aqueous Environments ◽

Delivery Vehicles ◽

Doxorubicin Release

Many promising pharmaceutically active compounds have low solubility in aqueous environments and their encapsulation into efficient drug delivery vehicles is crucial to increase their bioavailability. Lipodisq nanoparticles are approximately 10 nm in diameter and consist of a circular phospholipid bilayer, stabilized by an annulus of SMA (a hydrolysed copolymer of styrene and maleic anhydride). SMA is used extensively in structural biology to extract and stabilize integral membrane proteins for biophysical studies. Here, we assess the potential of these nanoparticles as drug delivery vehicles, determining their cytotoxicity and the in vivo excretion pathways of their polymer and lipid components. Doxorubicin-loaded Lipodisqs were cytotoxic across a panel of cancer cell lines, whereas nanoparticles without the drug had no effect on cell proliferation. Intracellular doxorubicin release from Lipodisqs in HeLa cells occurred in the low-pH environment of the endolysosomal system, consistent with the breakdown of the discoidal structure as the carboxylate groups of the SMA polymer become protonated. Biodistribution studies in mice showed that, unlike other nanoparticles injected intravenously, most of the Lipodisq components were recovered in the colon, consistent with rapid uptake by hepatocytes and excretion into bile. These data suggest that Lipodisqs have the potential to act as delivery vehicles for drugs and contrast agents.

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