Nanotechnologies for early diagnosis, in situ disease monitoring, and prevention

Abstract

Nanotechnology is an enabling technology with great potential for applications in stem cell research and regenerative medicine. Fluorescent nanodiamond (FND), an inherently biocompatible and nontoxic nanoparticle, is well suited for such applications. We had developed a prospective isolation method using CD157, CD45, and CD54 to obtain lung stem cells. Labeling of CD45 ⁻CD54 ⁺CD157 ⁺ cells with FNDs did not eliminate their abilities for self-renewal and differentiation. The FND labeling in combination with cell sorting, fluorescence lifetime imaging microscopy, and immunostaining identified transplanted stem cells allowed tracking of their engraftment and regenerative capabilities with single-cell resolution. Time-gated fluorescence (TGF) imaging in mouse tissue sections indicated that they reside preferentially at the bronchoalveolar junctions of lungs, especially in naphthalene-injured mice. Our results presented in Subchapter 1.1 demonstrate not only the remarkable homing capacity and regenerative potential of the isolated stem cells, but also the ability of finding rare lung stem cells in vivo using FNDs.

The topical use of antiretroviral-based microbicides, namely of a dapivirine ring, has been recently shown to partially prevent transmission of HIV through the vaginal route. Among different formulation approaches, nanotechnology tools and principles have been used for the development of tentative vaginal and rectal microbicide products. Subchapter 1.2 provides an overview of antiretroviral drug nanocarriers as novel microbicide candidates and discusses recent and relevant research on the topic. Furthermore, advances in developing vaginal delivery platforms for the administration of promising antiretroviral drug nanocarriers are reviewed. Although mostly dedicated to the discussion of nanosystems for vaginal use, the development of rectal nanomicrobicides is also addressed.

Infectious diseases are currently responsible for over 8 million deaths per year. Efficient treatments require accurate recognition of pathogens at low concentrations, which in the case of blood infection (septicemia) can go as low as 1 mL ^–1. Detecting and quantifying bacteria at such low concentrations is challenging and typically demands cultures of large samples of blood (∼1 mL) extending over 24–72 h. This delay seriously compromises the health of patients and is largely responsible for the death toll of bacterial infections. Recent advances in nanoscience, spectroscopy, plasmonics, and microfluidics allow for the development of optical devices capable of monitoring minute amounts of analytes in liquid samples. In Subchapter 1.3 we critically discuss these recent developments that will, in the future, enable the multiplex identification and quantification of microorganisms directly on their biological matrix with unprecedented speed, low cost, and sensitivity.

Radiolabeled nanoparticles (NPs) are finding an increasing interest in a broad range of biomedical applications. They may be used to detect and characterize diseases, to deliver relevant therapeutics, and to study the pharmacokinetic/pharmacodynamic parameters of nanomaterials. The use of radiotracer techniques in the research of novel NPs offers many advantages, but there are still some limitations. The binding of radionuclides to NPs has to be irreversible to prevent their escape to other tissues or organs. Due to the short half-lives of radionuclides, the manufacturing process is time limited and difficult, and there is also a risk of contamination. Subchapter 1.4 presents the main selection criteria for radionuclides and applicable radiolabeling procedures used for the radiolabeling of various NPs. Also, an overview of different types of NPs that have so far been labeled with radionuclides is presented.