A Kidney-Targeted Nanoparticle to Augment Renal Lymphatic Density Decreases Blood Pressure in Hypertensive Mice

Abstract

Chronic interstitial inflammation and renal infiltration of activated immune cells play an integral role in hypertension. Lymphatics regulate inflammation through clearance of immune cells and excess interstitial fluid. Previously, we demonstrated increasing renal lymphangiogenesis prevents hypertension in mice. We hypothesized that targeted nanoparticle delivery of vascular endothelial growth factor-C (VEGF-C) to the kidney would induce renal lymphangiogenesis, lowering blood pressure in hypertensive mice. A kidney-targeting nanoparticle was loaded with a VEGF receptor-3-specific form of VEGF-C and injected into mice with angiotensin II-induced hypertension or LNAME-induced hypertension every 3 days. Nanoparticle-treated mice exhibited increased renal lymphatic vessel density and width compared to hypertensive mice injected with VEGF-C alone. Nanoparticle-treated mice exhibited decreased systolic blood pressure, decreased pro-inflammatory renal immune cells, and increased urinary fractional excretion of sodium. Our findings demonstrate that pharmacologically expanding renal lymphatics decreases blood pressure and is associated with favorable alterations in renal immune cells and increased sodium excretion.

Metal‐based nanomaterials and nanocomposites as promising frontier in cancer chemotherapy

“… 245 The shape, size, and core chemical characteristics of NPs are all important factors in cellular uptakes, like spherical, cubic, rod shape, or worm shape, which have a significant impact on cellular uptake and anticancer properties. 246 When cubic, spherical, and rodlike AuNPs are compared, spherical NPs found to have the higher uptake in terms of weight, and rod‐shaped NPs demonstrate the large uptake in terms of quantity. 247 The circulation period improved as the size of AuNPs increased from 5 to 25 nm.…”

“…For example, the pore diameters of malignancies in the cranial window are significantly smaller than those found in the dorsal chamber; the size of the NPs must be adjusted to the type and location of the tumor 245 . The shape, size, and core chemical characteristics of NPs are all important factors in cellular uptakes, like spherical, cubic, rod shape, or worm shape, which have a significant impact on cellular uptake and anticancer properties 246 . When cubic, spherical, and rodlike AuNPs are compared, spherical NPs found to have the higher uptake in terms of weight, and rod‐shaped NPs demonstrate the large uptake in terms of quantity 247 .…”

Sodium, Interstitium, Lymphatics and Hypertension—A Tale of Hydraulics

“…The BP lowering and the renoprotective effects are in keeping with independent reports of salt-loaded mice treated with subcutaneous VEGF-C, 89 or its targeted delivery to the kidney with nanoparticles. 90 Although BP assessment relied only on tail cuff methods in these studies, data on correlated renal interstitial hydrostatic pressure changes are missing and whether an expanded lymphatic network results in an increased total lymph flow or alters interstitial fluid volume 91 remains to be established, it is safe to conclude that targeting VEGFR-3 in the kidney shows promise in opposing renal sodium retention and decreasing BP.…”

Update on Immune Mechanisms in Hypertension

“…This was able to decrease renal pro-inflammatory immune cells and blood pressure in mice with various forms of hypertension. 33 , 34 …”