Macrophage Delivery of Therapeutic Nanozymes in A Murine Model of Parkinson‘S Disease

Brynskikh, Anna M.; Zhao, Yanxin; Mosley, R. Lee; Li, Shu; Boska, Michael D.; Klyachko, Natalia L.; Kabanov, Alexander V.; Gendelman, Howard E.; Batrakova, Elena V.

doi:10.2217/nnm.10.7

Cited by 156 publications

(138 citation statements)

References 51 publications

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“…The idea of targeting activated macrophages to convert them to a normal phenotype has been proposed, however in many cases the cell surface biomarkers for abnormal activity and the regulatory effector molecules to revert activated macrophages are yet to be identified [9, 11-13]. By contrast, delivery of drugs to infected macrophages using nanocarriers (NCs) or cell carriers has been extensively explored [14-19]. …”

Section: Introductionmentioning

confidence: 99%

Optimal structural design of mannosylated nanocarriers for macrophage targeting

Chen

Zhang

Jia

et al. 2014

Journal of Controlled Release

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Macrophages are involved in a number of diseases, such as HIV infection/AIDS, tuberculosis, tumor development and atherosclerosis. Macrophages possess several cell surface receptors (e.g., the mannose receptor, MR) that may serve as drug delivery cellular portals for nanocarriers (NCs). In this study, the optimal structural configuration for cell uptake of mannosylated poly(ethylene glycol)-conjugate type NCs was determined. A series NCs was synthesized to systematically evaluate the effects of the number of mannose units (Man), the PEG carrier size and the mPEG spacer length between adjacent mannose units on NC uptake into MR-expressing J774.E murine macrophage-like cells. Among NCs with 0, 1, 2 or 4 units of mannose, the uptake of (Man)2-NC was the highest, suggesting a trade-off between avidity and NC-MR clustering on the cell surface that sterically hinders endocytosis. This optimal (Man)2-NC configuration was built into subsequent NCs to optimize the other two parameters, PEG carrier size and spacer length. NCs with 0, 5, 12, 20, 30 or 40 kDa linear PEG carriers showed an inverse relationship between PEG size and uptake. The 12 kDa PEG carrier was chosen for investigating the third parameter, the Man-Man distance, since it may represent the best trade off (i.e., tissue penetration vs. systemic clearance) for in vivo macrophage targeting. Three (Man)2-PEG12kDa NCs with different Man-Man distances (39, 56 or 89 Å) were synthesized. The uptake of the NC with the 56 Å distance between mannoses was four- and two-fold higher than NCs with 39 Å and 89 Å distances, respectively. Confocal microscopy confirmed that the optimized (Man)2-PEG12kDa NC with the 56 Å Man-Man distance was internalized via endocytosis consistent with temperature-dependent active uptake. In conclusion, the optimal NC structural parameters for targeting the MR on macrophage-like J774.E cells are (i) a small PEG polymer carrier, (ii) two mannose units per NC and (iii) a 56 Å distance between adjacent mannose units.

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Section: Introductionmentioning

confidence: 99%

Optimal structural design of mannosylated nanocarriers for macrophage targeting

Chen

Zhang

Jia

et al. 2014

Journal of Controlled Release

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“…The MSC-NP system overcame blood-brain barrier and actively targeted orthotropic glioma. In order to evaluate the homing capability of NPs with MSCs, HA- (Brynskikh et al, 2010). Cu with the same amount of radioactivity was also injected as a control, PET imaging demonstrated that there was a 5.2 ± 1.3-fold higher tumor accumulation in the glioma by MSC-HA-MSN-64 Cu within 24 h after injection than the free HA-MSN-64 Cu (Huang et al, 2013).…”

Section: Stem Cellsmentioning

confidence: 99%

A novel strategy to achieve effective drug delivery: exploit cells as carrier combined with nanoparticles

et al. 2017

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Cell-mediated drug delivery systems employ specific cells as drug vehicles to deliver drugs to targeted sites. Therapeutics or imaging agents are loaded into these cells and then released in diseased sites. These specific cells mainly include red blood cells, leukocytes, stem cells and so on. The cell acts as a Trojan horse to transfer the drug from circulating blood to the diseased tissue. In such a system, these cells keep their original properties, which allow them to mimic the migration behavior of specific cells to carry drug to the targeted site after in vivo administration. This strategy elegantly combines the advantages of both carriers, i.e. the adjustability of nanoparticles (NPs) and the natural functions of active cells, which therefore provides a new perspective to challenge current obstacles in drug delivery. This review will describe a fundamental understanding of these cell-based drug delivery systems, and discuss the great potential of combinational application of cell carrier and NPs.

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“…Cell-mediated delivery of nanoformulations has gained increasing attention for the treatment of various brain diseases, including brain cancer [133], neurodegenerative disorders [134], and HAND [111, 135]. Parkinson’s disease has been one of the first targets for cell-based therapy [136].…”

Section: Art Nanomedicinesmentioning

confidence: 99%

Development of HIV Reservoir Targeted Long Acting Nanoformulated Antiretroviral Therapies

Edagwa¹,

Zhou²,

McMillan³

et al. 2014

CMC

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Human immunodeficiency virus (HIV) infection commonly results in a myriad of comorbid conditions secondary to immune deficiency. Infection also affects broad organ system function. Although current antiretroviral therapy (ART) reduces disease morbidity and mortality through effective control of peripheral viral load, restricted infection in HIV reservoirs including gut, lymphoid and central nervous system tissues, is not eliminated. What underlies these events is, in part, poor ART penetrance into each organ across tissue barriers, viral mutation and the longevity of infected cells. We posit that one means to improve these disease outcomes is through nanotechnology. To this end, this review discusses a broad range of cutting-edge nanomedicines and nanomedicine platforms that are or can be used to improve ART delivery. Discussion points include how polymer-drug conjugates, dendrimers, micelles, liposomes, solid lipid nanoparticles and polymeric nanoparticles can be harnessed to best yield cell-based delivery systems. When completely developed, such nanomedicine platforms have the potential to clear reservoirs of viral infection.

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Macrophage Delivery of Therapeutic Nanozymes in A Murine Model of Parkinson‘S Disease

Cited by 156 publications

References 51 publications

Optimal structural design of mannosylated nanocarriers for macrophage targeting

Optimal structural design of mannosylated nanocarriers for macrophage targeting

A novel strategy to achieve effective drug delivery: exploit cells as carrier combined with nanoparticles

Development of HIV Reservoir Targeted Long Acting Nanoformulated Antiretroviral Therapies

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