Immuno-silent polymer capsules encapsulating nanoparticles for bioimaging applications.

PEGylated polymer capsules encapsulating LaVO4:Tb3+, GdVO4:Tb3+, Gd2O3:Tb3+, GdF3:Tb3+, YVO4:Tb3+ and iron oxide nanoparticles are promising new fluorescence, magnetic and magnetofluorescence imaging agents. Recently, we have reported their in vitro and in vivo level toxicity profiles which show the non-toxic nature of these polymer capsules encapsulating nanoparticles. However, prior to clinical use, it is essential to ensure that these agents are unlikely to activate immune responses. Herein, we investigated the immunocompatibility of polymer capsules with dendritic cells (DCs), macrophages (MOs), and major antigen presenting cell (APC) subsets required for the activation of innate and adaptive immunity. The capsules were efficiently internalized by both DCs and MOs in vitro. Importantly, despite the presence of intracellular capsules, there was no significant impact on the viability of the cells. We studied the impact of different capsules on the cytokine profiles of the DCs and MOs, which is known to be important for the polarization of T-cell immunity. None of the capsules elicited a change in cytokine secretion from the DCs. Furthermore, the capsules did not alter the polarization of either M1 or M2 MO subsets as determined by the balance of IL-12 and IL-10 secretion. These data support the notion that PEGylated polymer capsules loaded with nanoparticles have the potential to remain immunologically silent as they do not activate APCs nor do they hinder the response of DCs or MOs to pathogen activating signals. These systems, therefore, exhibit promising characteristics for bioimaging applications.

Targeted Stealth Polymer Capsules Encapsulating Ln3+-Doped LaVO4 Nanoparticles for Bioimaging Applications.

We report synthesis of targeted PEGylated polymer capsules encapsulating Stoke's shift and upconverting LaVO4 nanoparticles by following a unique approach for bioimaging applications. First, LaVO4:Ln3+@silica (Ln3+ = Tb3+, Eu3+, and Yb3+/Er3+) core-shell nanoparticles are prepared by sol-gel method followed by layer-by-layer assembly of polymers and PEGylation over core-shell particles. Second, removal of silica core facilitates the trapping of LaVO4:Ln3+ nanoparticles inside the PEGylated polymer capsules. Finally, capsules are surface modified with antibodies to target cancer cells. The nanoparticles-loaded polymer capsules are found to be internalized and biocompatible with various cells (e.g., HeLa, A498, H460, MCF-7, Schwann, L929, and IC-21) suggesting their applicability in different types of cells. In addition, the capsules modified with antibodies show more specific uptake suggesting their targeting ability by 3-fold for MCF-7 and 10-fold for H460 cancer cells. Moreover, the nanoparticle-loaded polymer capsules were internalized by HeLa cells via macropinocytosis mechanism. We observed localized bright Stoke's shift (Tb3+ ions, λex = 488 nm) and upconversion (Er3+ ions, λex = 980 nm) green fluorescence from cells suggesting their potential use as targeted bioimaging agents.