Nanoparticle delivery in vivo: A fresh look from intravital imaging

Lin, Qiaoya; Fathi, Parinaz; Chen, Xiaoyuan

doi:10.1016/j.ebiom.2020.102958

Cited by 27 publications

(15 citation statements)

References 68 publications

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“…The shape, size and surface potential could also affect endocytosis and targeting of nanoparticles. For instance, neutrophils are more likely to uptake negatively-charged, cube-shaped, >100 nm sized nanoparticles 162 . Different delivery systems present different requirements for the design, and thus it needs to be carefully optimized during the preclinical study.…”

Section: Discussion and Perspectivesmentioning

confidence: 99%

Receptor-mediated targeted drug delivery systems for treatment of inflammatory bowel disease: Opportunities and emerging strategies

Liu

Gao

Hong-guo

et al. 2021

Acta Pharmaceutica Sinica B

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Inflammatory bowel disease (IBD) is a chronic intestinal disease with painful clinical manifestations and high risks of cancerization. With no curative therapy for IBD at present, the development of effective therapeutics is highly advocated. Drug delivery systems have been extensively studied to transmit therapeutics to inflamed colon sites through the enhanced permeability and retention (EPR) effect caused by the inflammation. However, the drug still could not achieve effective concentration value that merely utilized on EPR effect and display better therapeutic efficacy in the inflamed region because of nontargeted drug release. Substantial researches have shown that some specific receptors and cell adhesion molecules highly expresses on the surface of colonic endothelial and/or immune cells when IBD occurs, ligand-modified drug delivery systems targeting such receptors and cell adhesion molecules can specifically deliver drug into inflamed sites and obtain great curative effects. This review introduces the overexpressed receptors and cell adhesion molecules in inflamed colon sites and retrospects the drug delivery systems functionalized by related ligands. Finally, challenges and future directions in this field are presented to advance the development of the receptor-mediated targeted drug delivery systems for the therapy of IBD.

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Section: Discussion and Perspectivesmentioning

confidence: 99%

Receptor-mediated targeted drug delivery systems for treatment of inflammatory bowel disease: Opportunities and emerging strategies

Liu

Gao

Hong-guo

et al. 2021

Acta Pharmaceutica Sinica B

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“…[10,12,13] Although there are many advantages, traditional administration of these drugs causes off-target accumulation and serious systemic adverse effects; [14][15][16] however, the delivery of nanomaterials remains limited by uncertain clearance mechanisms, poor maneuverability, and complex synthetic processes. [17][18][19] Thus, new drug carriers with improved administration techniques and biosecurity, as well as effective tumor-targeting, are required.…”

Section: Introductionmentioning

confidence: 99%

Ultrasound‐Responsive Microfluidic Microbubbles for Combination Tumor Treatment

Huang

Zhang

Zhao

et al. 2021

Advanced Therapeutics

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Anticancer treatment is a worldwide challenge, and there are constant endeavors in this field to develop intelligent drug delivery systems to improve the therapeutic effect. This paper presents novel ultrasound-responsive delivery microbubbles (UDMs), with chemotherapeutic-encapsulated hydrogel shells and therapeutic gas cores. These are developed using microfluidic electrospray to treat pancreatic tumors. As the hydrogel shells are composed of thermo-sensitive poly(N-isopropylacrylamide) (PNIPAM), they can contract under mild hyperthermia generated by the acoustic-wave-induced oscillation of the encapsulated gas. Thus, by triggering with ultrasound, the chemotherapeutic Gemcitabine (Gem) encapsulated in the hydrogel shells and the hydrogen sulfide (H 2 S) encased in the cores can be controllably released. Based on the UDMs, it is demonstrated that the multiple drug-loaded microcarriers exhibit an excellent tumor-killing effect through combination therapy. The Gem and H 2 S coloaded UDMs have good therapeutic efficacy and adaptability in an orthotopic pancreatic implantation tumor model established in mice. These results indicate that the proposed UDMs have a large potential for codelivery of multiple drugs for treating deep-seated tumors and for realizing combination drug treatment to avoid untoward reactions.

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“…Generally, PEG has been shown to enhance systemic circulation and blood endothelium needs to be targeted using additional vectors such as ICAM1 or sugars that target specific ligands on the blood endothelium [28, 29]. This is likely due to the high flow rates in blood vessels that cause nanoparticles not to come into close contact with endothelial cells for long enough to allow uptake and transport across the endothelium [30, 31]. A recent study used 100 nm poly(lactic acid)-PEG nanoparticles with surface PEG ranging from 1 – 10 kDa to probe the effects of PEG MW on transcytosis across brain vascular endothelial monolayers [32].…”

Section: Discussionmentioning

confidence: 99%

Dense poly(ethylene glycol) coatings maximize nanoparticle transport across lymphatic endothelial cells and accumulate in the skindraining lymph nodes

McCright

Skeen

Yarmovsky

et al. 2020

Preprint

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Lymphatic vessels have received considerable attention in recent years as delivery route for immune modulatory therapies to the lymph nodes. Lymph node targeting of immunotherapies and vaccines has been shown to significantly enhance their therapeutic efficacy. Lymphatics transport functions materials from peripheral tissues to the lymph nodes, including small 10 – 250 nm therapeutic nanoparticles. While size required to enter lymphatic vessels, surface chemistry is more poorly studied. Here, we probed the effects of surface poly(ethylene glycol) (PEG) density on nanoparticle transport across lymphatic endothelial cells (LECs). We differentially PEGylated model carboxylate-modified polystyrene nanoparticles to form either a brush or dense brush PEG conformation on the nanoparticle surfaces. Using an established in-vitro lymphatic transport model, we found that the addition of any PEG improved the transport of nanoparticles through lymphatic endothelial cells (2.5 - 2.6 ± 0.9% transport efficiency at 24 hours) compared to the unmodified PS-COOH nanoparticles (0.05 ± 0.05% transport efficiency at 24 hours). Additionally, we found that transcellular transport is maximized (4.2 ± 0.7% transport efficiency at 24 hours) when the PEG is in a dense brush conformation on nanoparticle surfaces, corresponding with a high grafting density (Rf/D = 4.9). These results suggest that PEG conformation has a crucial role in determining translocation of nanoparticles across LECs and into lymphatic vessels. Thus, we identified PEG density as a major design criteria for maximizing lymphatic targeting of therapeutic nanoparticle formulations that can be widely applied to enhance immunotherapeutic and vaccine outcomes in future studies.

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Nanoparticle delivery in vivo: A fresh look from intravital imaging

Cited by 27 publications

References 68 publications

Receptor-mediated targeted drug delivery systems for treatment of inflammatory bowel disease: Opportunities and emerging strategies

Receptor-mediated targeted drug delivery systems for treatment of inflammatory bowel disease: Opportunities and emerging strategies

Ultrasound‐Responsive Microfluidic Microbubbles for Combination Tumor Treatment

Dense poly(ethylene glycol) coatings maximize nanoparticle transport across lymphatic endothelial cells and accumulate in the skindraining lymph nodes

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