Nanomedicines for dysfunctional macrophage-associated diseases

He, Hongliang; Ghosh, Shobha; Yang, Hu

doi:10.1016/j.jconrel.2016.12.032

Cited by 45 publications

(32 citation statements)

References 227 publications

(191 reference statements)

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“…Targeting macrophages by their physiological ability to uptake particles is currently being proposed as a therapy for a number of diseases where macrophages are implicated, including chronic inflammation, metabolic diseases, fibrotic diseases, and cancer . Furthermore, this approach is being considered for viral infection, where macrophages are viral reservoirs, such as in acquired immune deficiency syndrome, or for chronic bacterial infection for instance in tuberculosis, where alveolar macrophages are reservoirs of the pathogenic Mycobacterium tuberculosis . In addition, the large proportion of capsules evading uptake by phagocytes in the lung at 20 h provides opportunities for targeting other cell populations for local drug delivery.…”

Section: Resultsmentioning

confidence: 99%

“…[41] Furthermore, this approach is being considered for viral infection, where macrophages are viral reservoirs, such as in acquired immune deficiency syndrome, or for chronic bacterial infection for instance in tuberculosis, where alveolar macrophages are reservoirs of the pathogenic Mycobacterium tuberculosis. [42] In addition, the large proportion of capsules evading uptake by phagocytes in the lung at 20 h provides opportunities for targeting other cell populations for local drug delivery.…”

Section: In Vivo Assessment Of Lung Cell Association Inflammation Amentioning

confidence: 99%

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Engineering of Nebulized Metal–Phenolic Capsules for Controlled Pulmonary Deposition

Cortez‐Jugo

Chen

et al. 2020

Advanced Science

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Particle‐based pulmonary delivery has great potential for delivering inhalable therapeutics for local or systemic applications. The design of particles with enhanced aerodynamic properties can improve lung distribution and deposition, and hence the efficacy of encapsulated inhaled drugs. This study describes the nanoengineering and nebulization of metal–phenolic capsules as pulmonary carriers of small molecule drugs and macromolecular drugs in lung cell lines, a human lung model, and mice. Tuning the aerodynamic diameter by increasing the capsule shell thickness (from ≈100 to 200 nm in increments of ≈50 nm) through repeated film deposition on a sacrificial template allows precise control of capsule deposition in a human lung model, corresponding to a shift from the alveolar region to the bronchi as aerodynamic diameter increases. The capsules are biocompatible and biodegradable, as assessed following intratracheal administration in mice, showing >85% of the capsules in the lung after 20 h, but <4% remaining after 30 days without causing lung inflammation or toxicity. Single‐cell analysis from lung digests using mass cytometry shows association primarily with alveolar macrophages, with >90% of capsules remaining nonassociated with cells. The amenability to nebulization, capacity for loading, tunable aerodynamic properties, high biocompatibility, and biodegradability make these capsules attractive for controlled pulmonary delivery.

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Section: Resultsmentioning

confidence: 99%

Section: In Vivo Assessment Of Lung Cell Association Inflammation Amentioning

confidence: 99%

Engineering of Nebulized Metal–Phenolic Capsules for Controlled Pulmonary Deposition

Cortez‐Jugo

Chen

et al. 2020

Advanced Science

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“…Macrophages in tumor tissues (TAMs) are mostly M2-like cells that produce tumor-promoting cytokines and growth factors that promote tumor expansion, angiogenesis, metastasis, and immune cell evasion. TAMs also contribute to drug resistance (27,28).…”

Section: Role Of Kupffer Cells In Hepatic Diseases: Cytokines and Chementioning

confidence: 99%

Targeting of Hepatic Macrophages by Therapeutic Nanoparticles

2020

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“…With the advancement of nanotechnology, development of nanomedicines to efficiently target dysfunctional macrophages can strengthen the effectiveness of therapeutics and improve clinical outcomes. 1 Several macrophage-specific surface receptors have been described including mannose receptor, 2 folate receptor, 3 and TIM-4 or BAI-1 4,5 that can potentially be used for effective targeting. Although folate-functionalized nanomedicine to target cancerous tissue-associated macrophages has been described 6 ; strategies to target dysfunctional macrophages in other chronic diseases such as atherosclerosis are very limited.…”

Section: Introductionmentioning

confidence: 99%

Development of mannose functionalized dendrimeric nanoparticles for targeted delivery to macrophages: use of this platform to modulate atherosclerosis

Yuan

Bie

et al. 2018

Translational Research

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Dysfunctional macrophages underlie the development of several diseases including atherosclerosis where accumulation of cholesteryl esters and persistent inflammation are 2 of the critical macrophage processes that regulate the progression as well as stability of atherosclerotic plaques. Ligand-dependent activation of liver-x-receptor (LXR) not only enhances mobilization of stored cholesteryl ester but also exerts anti-inflammatory effects mediated via trans-repression of proinflammatory transcription factor nuclear factor kappa B. However, increased hepatic lipogenesis by systemic administration of LXR ligands (LXR-L) has precluded their therapeutic use. The objective of the present study was to devise a strategy to selectively deliver LXR-L to atherosclerotic plaque-associated macrophages while limiting hepatic uptake. Mannose-functionalized dendrimeric nanoparticles (mDNP) were synthesized to facilitate active uptake via the mannose receptor expressed exclusively by macrophages using polyamidoamine dendrimer. Terminal amine groups were used to conjugate mannose and LXR-L T091317 via polyethylene glycol spacers. mDNPLXR-L was effectively taken up by macrophages (and not by hepatocytes), increased expression of LXR target genes (ABCA1/ABCG1), and enhanced cholesterol efflux. When administered intravenously to LDLR−/− mice with established plaques, significant accumulation of fluorescently labeled mDNP-LXR-L was seen in atherosclerotic plaque-associated macrophages. Four weekly injections of mDNP-LXR-L led to significant reduction in atherosclerotic plaque progression, plaque necrosis, and plaque inflammation as assessed by expression of nuclear factor kappa B target gene matrix metalloproteinase 9; no increase in hepatic lipogenic genes or plasma lipids was observed. These studies validate the development of a macrophage-specific delivery platform for the delivery of anti-atherosclerotic agents directly to the plaque-associated macrophages to attenuate plaque burden.

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Nanomedicines for dysfunctional macrophage-associated diseases

Cited by 45 publications

References 227 publications

Engineering of Nebulized Metal–Phenolic Capsules for Controlled Pulmonary Deposition

Engineering of Nebulized Metal–Phenolic Capsules for Controlled Pulmonary Deposition

Targeting of Hepatic Macrophages by Therapeutic Nanoparticles

Development of mannose functionalized dendrimeric nanoparticles for targeted delivery to macrophages: use of this platform to modulate atherosclerosis

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