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Co-coating of receptor-targeted drug nanocarriers with anti-phagocytic moieties enhances specific tissue uptake versus non-specific phagocytic clearance.

ABSTRACT: Nanocarriers (NCs) help improve the performance of therapeutics, but their removal by phagocytes in the liver, spleen, tissues, etc. diminishes this potential. Although NC functionalization with polyethylene glycol (PEG) lowers interaction with phagocytes, it also reduces interactions with tissue cells. Coating NCs with CD47, a protein expressed by body cells to avoid phagocytic removal, offers an alternative. Previous studies showed that coating CD47 on non-targeted NCs reduces phagocytosis, but whether this alters binding and endocytosis of actively-targeted NCs remains unknown. To evaluate this, we used polymer NCs targeted to ICAM-1, a receptor overexpressed in many diseases. Co-coating of CD47 on anti-ICAM NCs reduced macrophage phagocytosis by ?50% for up to 24 h, while increasing endothelial-cell targeting by ?87% over control anti-ICAM/IgG NCs. Anti-ICAM/CD47 NCs were endocytosed via the CAM-mediated pathway with efficiency similar (0.99-fold) to anti-ICAM/IgG NCs. Comparable outcomes were observed for NCs targeted to PECAM-1 or transferrin receptor, suggesting broad applicability. When injected in mice, anti-ICAM/CD47 NCs reduced liver and spleen uptake by ?30-50% and increased lung targeting by ?2-fold (?10-fold over IgG NCs). Therefore, co-coating NCs with CD47 and targeting moieties reduces macrophage phagocytosis and improves targeted uptake. This strategy may significantly improve the efficacy of targeted drug NCs.

SUBMITTER: Kim J

PROVIDER: S-EPMC5667353 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Co-coating of receptor-targeted drug nanocarriers with anti-phagocytic moieties enhances specific tissue uptake versus non-specific phagocytic clearance.

Kim Joshua J Sinha Sauradeep S Solomon Melani M Perez-Herrero Edgar E Hsu Janet J Tsinas Zois Z Muro Silvia S

Biomaterials 20170906

Nanocarriers (NCs) help improve the performance of therapeutics, but their removal by phagocytes in the liver, spleen, tissues, etc. diminishes this potential. Although NC functionalization with polyethylene glycol (PEG) lowers interaction with phagocytes, it also reduces interactions with tissue cells. Coating NCs with CD47, a protein expressed by body cells to avoid phagocytic removal, offers an alternative. Previous studies showed that coating CD47 on non-targeted NCs reduces phagocytosis, bu ...[more]

PMID: 28923682

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Project description:Zinc oxide nanoparticles (ZnO-NPs) hold promise as novel fertilizer nutrients for crops. However, their ultra-small size could hinder large-scale field application due to potential for drift, untimely dissolution or aggregation. In this study, urea was coated with ZnO-NPs (1%) or bulk ZnO (2%) and evaluated in wheat (Triticum aestivum L.) in a greenhouse, under drought (40% field moisture capacity; FMC) and non-drought (80% FMC) conditions, in comparison with urea not coated with ZnO (control), and urea with separate ZnO-NP (1%) or bulk ZnO (2%) amendment. Plants were exposed to ? 2.17 mg/kg ZnO-NPs and ? 4.34 mg/kg bulk-ZnO, indicating exposure to a higher rate of Zn from the bulk ZnO. ZnO-NPs and bulk-ZnO showed similar urea coating efficiencies of 74-75%. Drought significantly (p ? 0.05) increased time to panicle initiation, reduced grain yield, and inhibited uptake of Zn, nitrogen (N), and phosphorus (P). Under drought, ZnO-NPs significantly reduced average time to panicle initiation by 5 days, irrespective of coating, and relative to the control. In contrast, bulk ZnO did not affect time to panicle initiation. Compared to the control, grain yield increased significantly, 51 or 39%, with ZnO-NP-coated or uncoated urea. Yield increases from bulk-ZnO-coated or uncoated urea were insignificant, compared to both the control and the ZnO-NP treatments. Plant uptake of Zn increased by 24 or 8% with coated or uncoated ZnO-NPs; and by 78 or 10% with coated or uncoated bulk-ZnO. Under non-drought conditions, Zn treatment did not significantly reduce panicle initiation time, except with uncoated bulk-ZnO. Relative to the control, ZnO-NPs (irrespective of coating) significantly increased grain yield; and coated ZnO-NPs enhanced Zn uptake significantly. Zn fertilization did not significantly affect N and P uptake, regardless of particle size or coating. Collectively, these findings demonstrate that coating urea with ZnO-NPs enhances plant performance and Zn accumulation, thus potentiating field-scale deployment of nano-scale micronutrients. Notably, lower Zn inputs from ZnO-NPs enhanced crop productivity, comparable to higher inputs from bulk-ZnO. This highlights a key benefit of nanofertilizers: a reduction of nutrient inputs into agriculture without yield penalities.

Dataset Information

Co-coating of receptor-targeted drug nanocarriers with anti-phagocytic moieties enhances specific tissue uptake versus non-specific phagocytic clearance.

Publications

Co-coating of receptor-targeted drug nanocarriers with anti-phagocytic moieties enhances specific tissue uptake versus non-specific phagocytic clearance.

Similar Datasets

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