Prolonged Dye Release from Mesoporous Silica-Based Imaging Probes Facilitates Long-Term Optical Tracking of Cell Populations In Vivo

Abstract

Nanomedicine is gaining ground worldwide in therapy and diagnostics. Novel nanoscopic imaging probes serve as imaging tools for studying dynamic biological processes in vitro and in vivo. To allow detectability in the physiological environment, the nanostructure-based probes need to be either inherently detectable by biomedical imaging techniques, or serve as carriers for existing imaging agents. In this study, the potential of mesoporous silica nanoparticles carrying commercially available fluorochromes as self-regenerating cell labels for long-term cellular tracking is investigated. The particle surface is organically modified for enhanced cellular uptake, the fluorescence intensity of labeled cells is followed over time both in vitro and in vivo. The particles are not exocytosed and particles which escaped cells due to cell injury or death are degraded and no labeling of nontargeted cell populations are observed. The labeling efficiency is significantly improved as compared to that of quantum dots of similar emission wavelength. Labeled human breast cancer cells are xenotransplanted in nude mice, and the fluorescent cells can be detected in vivo for a period of 1 month. Moreover, ex vivo analysis reveals fluorescently labeled metastatic colonies in lymph node and rib, highlighting the capability of the developed probes for tracking of metastasis.

Factors Affecting Intracellular Delivery and Release of Hydrophilic Versus Hydrophobic Cargo from Mesoporous Silica Nanoparticles on 2D and 3D Cell Cultures

“…Namely, a higher amount of hydrophobic cargo loading would lead to an increased hydrophobicity of the overall drug carrier system, which could have implications on the release rate in terms of delayed release [38] with increased loading of hydrophobic agents. Consequently, a higher loading degree could provide a release of cargo over a prolonged period of time [39]. In our earlier studies, we have clearly observed a delayed but efficient intracellular release within a couple of days [37,39] when using hydrophobic dye molecules at a loading degree of 5 wt %, in spite of hardly any release taking place under in vitro conditions in buffer solution only over a time course of one week [22].…”

Multimodality Imaging of Silica and Silicon Materials In Vivo

“…A) The cells were visible for a period of 32 d. B,C) Ex vivo imaging of isolated organs verified tumor labeling and allowed for the detection of metastatic colonies. Reproduced with permission . Copyright 2016, Wiley‐VCH.…”

Tailored Approaches in Drug Development and Diagnostics: From Molecular Design to Biological Model Systems

“…Nanoscopic imaging probes have already made significant progress in overcoming limitations associated with conventional, molecular imaging agents . The nanostructures essentially can be either (1) inherently detectable by optical and biomedical imaging techniques, or (2) serve as carriers for existing, molecular imaging agents . Inorganic nanostructures are readily utilized as biomedical imaging probes due to their inherent detectability by a variety of different imaging modalities, for example, quantum dots, QDs, for optical imaging and superparamagnetic iron oxides, SPIONs, for magnetic resonance imaging (MRI).…”

“…With respect to drug delivery to inflammatory bowel diseases such as ulcerative colitis, novel material‐based rectal formulations have shown successful facilitation of mucosal healing by using drugs in hydrogels to target the inflamed colonic mucosa or thermo‐sensitive polymer platforms in murine models of colitis. Development and use of in vivo diagnostic imaging modalities is essential to follow effects of drugs and disease progression over time, for example, for intestinal inflammation by optical imaging and PET or optical imaging of cancer growth . A crucial challenge in utilizing nanodiagnostics if the nanoparticles carry the diagnostic probe is particle integrity (e.g., that the label remain attached to the particle during imaging).…”

“…The model is also well suited to assess vascularization of regenerating tissues and material‐based engineered tissues for regenerative medicine . The CAM model can thus be employed to evaluate drug delivery systems as well as functional materials in both cancer and regenerative therapies and to evaluate the utilization of cellular and molecular probes . The drawback of the system is that it is not human and that the chick embryos do not have a developed immune system during the experimental window.…”