Targeted drug delivery via caveolae-associated protein PV1 improves lung fibrosis

Abstract

Systemic administration of bio-therapeutics can result in only a fraction of drug reaching targeted tissues, with the majority of drug being distributed to tissues irrelevant to the drug’s site of action. Targeted delivery to specific organs may allow for greater accumulation, better efficacy, and improved safety. We investigated how targeting plasmalemma vesicle-associated protein (PV1), a protein found in the endothelial caveolae of lungs and kidneys, can promote accumulation in these organs. Using ex vivo fluorescence imaging, we show that intravenously administered αPV1 antibodies localize to mouse lungs and kidneys. In a bleomycin-induced idiopathic pulmonary fibrosis (IPF) mouse model, αPV1 conjugated to Prostaglandin E₂ (PGE₂), a known anti-fibrotic agent, significantly reduced collagen content and fibrosis whereas a non-targeted PGE₂ antibody conjugate failed to slow fibrosis progression. Our results demonstrate that PV1 targeting can be utilized to deliver therapeutics to lungs and this approach is potentially applicable for various lung diseases.

Marchetti et al. show that antibodies against Plasmalemma Vesicle Associated Protein (PV1) can be used to efficiently target drugs to lungs and kidneys. In a bleomycin induced lung fibrosis model, mice treated with anti-PV1 antibodies linked to an anti-fibrotic drug exhibited reduced collagen deposition and fibrosis progression compared to control antibodies.