RGDfK‐functionalized gold nanorods bind only to activated platelets

Abstract

Integrin-targeting peptide RGDfK-labeled gold nanorods (GNR) seek to improve hyperthermia targeted to solid tumors by exploiting the known up-regulation of integrin αvβ3 cell membrane proteins on solid tumor vasculature surfaces. Tumor binding specificity might be expected since surrounding tissues and endothelial cells have limited numbers of these receptors. However, RGD peptide binding to many proteins is promiscuous, with known affinity to several families of cell integrin receptors, and also possible binding to platelets after intravenous infusion via a different integrin receptor, αIIbβ3, on platelets. Binding of RGDfK-targeted GNR could considerably impact platelet function, ultimately leading to increased risk of bleeding or thrombosis depending on the degree of interaction. We sought to determine if RGDfK-labeled GNR could interact with platelets and alter platelet function. Targeted and untargeted nanorods exhibited little interaction with resting platelets in platelet rich plasma (PRP) preparations. However, upon platelet activation, peptide-targeted nanorods bound actively to platelets. Addition of RGDfK-GNR to unactivated platelets had little effect on markers of platelet activation, indicating that RGDfK-nanorods were incapable of inducing platelet activation. We next tested whether activated platelet function was altered in the presence of peptide-targeted nanorods. Platelet aggregation in whole blood and PRP in the presence of targeted nanorods had no significant effect on platelet aggregation. These data suggest that RGDfK-GNR alone have little impact on platelet function in plasma. However, nonspecific nanorod binding may occur in vascular beds where activated platelets are normally cleared, such as the spleen and liver, producing a possible toxicity risk for these nanomaterials.

Engineering docetaxel-loaded micelles for non-small cell lung cancer: a comparative study of microfluidic and bulk nanoparticle preparation

“…67 The IC 50 of DTMM was slightly lower than that of DMM (19.3 mM vs. 26.0 mM, P < 0.05), indicating the targeting effect of cyclic RGD. 68,69 Meanwhile, in the 3LL cell line, the IC 50 of DMM was also smaller than that of DMD (26.7 mM vs. 44.1 mM, P < 0.05) but was nearly identical to that of DTMM (26.7 mM vs. 26.3 mM, P < 0.05) (Fig. 3B), indicating that the targeting effect of RGDfK was greatly decreased.…”

Advances in Targeting Drug Biological Carriers for Enhancing Tumor Therapy Efficacy

“…Gold nanorods exposed to an external light source can convert light energy into heat, leading to further recruitment of platelet NPs from the circulation and resulting in platelet‐based “self‐enhancing” cell therapy. [ 103 ] Tumor cells need platelets to maintain tumor vascular integrity, one exploited this fact targeted DNA nanorobots (nanorobot – TH) to deliver to tumor vessels, triggering intratumor thrombosis, inducing vascular infarction, and ultimately tumor necrosis. [ 104 ] Using a smart polymer nanogel, permanent and peripheral embolization of liver tumors was achieved by simulating a coagulation cascade.…”

Platelets and platelet extracellular vesicles in drug delivery therapy: A review of the current status and future prospects

“…In this process, gold nanorods were used to treat squamous cell carcinoma via light heat treatment, whereby the nanorods convert light energy into heat energy under the irradiation of an external light source ( Rao et al, 2018 ). This injures the tumor cells, which leads to the further recruitment of platelet-nanoparticles from the circulation, thereby realizing a “self-enhancing” platelet-based cell therapy ( Zeller Meidell et al, 2017 ). In addition, some studies also encapsulated fluorescent beads, viruses, and other particles in engineered platelets to achieve targeted drug delivery via platelet-targeting properties ( Sarkar et al, 2013 ; Li et al, 2016 ; Xu et al, 2017 ).…”

“…While EXOs with nanometer diameters (30–100 nm) come from multivesicular bodies and α-granules by the endocytic pathway, which including proteins, mRNAs, and miRNAs ( Raposo and Stoorvogel, 2013 ). In majority studies, researchers refer to MPs and EXOs consistently as PEVs ( Zeller Meidell et al, 2017 ). Recent studies showed that, PEVs have been found to participate in a variety of biological processes via intercellular and intracellular communication ( Risitano et al, 2012 ; Laffont et al, 2013 ; Semple, 2013 ), including clotting ( Midura et al, 2016 ), angiogenesis ( Mause et al, 2010 ), inflammation ( Boilard et al, 2010 ), and tumor progression ( Cocucci et al, 2009 ; Helley et al, 2009 ).…”