Phosphors in Role of Magnetic Resonance, Medical Imaging and Drug Delivery Applications: A Review

Neha Dubey¹, Vikas Dubey², Jagjeet Kaur¹, Dhananjay Kumar Deshmukli³* and K.V.R. Murthy¹

• 1 Department of Physics, Govt. V.Y.T.PG. Auto. College, Durg - 491001, India
• 2 Department of Physics, Bhilai Institute of Technology Raipur, Kendri - 493661, India
• 3 Chubu Institute for Advance Studies, Chubu University, Kasugai - 487-8501, Japan
• 4 Fellow Luminescence Society of India, President, Luminescence Society of India, Applied Physics Department, Faculty of Technology and Engineering, M. S. University of Baroda, Baroda - 390001, India

Introduction

Metastasis—which accounts for 90% of cancer-related deaths (Chaffer and Weinberg 2011), and occurs when cancer cells detach from their primary site and home in distant organs—can be detected through non-invasive clinical- imaging modalities such as Magnetic Resonance Imaging (MRI), X-ray Computed Tomography (CT) and Positron Emission Tomography (PET) (O'Connor et al. 2011; Heinzmann et al. 2017). Contrast enhanced MRI is typically the preferred choice because of its higher sensitivity and specificity; yet CT, which is highly accessible and has lower operating costs, is used more widely. Although these imaging modalities are capable of detecting large metastases, they do not offer the resolution necessary to detect the early spread of metastatic tumor cells. Rare-earth-doped nanoprobes emitting short-wavelength infrared light enable the detection of metastatic lesions in multiple organs (Zh

In vivo fluorescence imaging in the near-infrared region between 1500-1700 nm (NIR-IIb window) affords high spatial resolution, deep- tissue penetration and diminished auto-fluorescence due to the suppressed ^Corresponding author: This email address is being protected from spam bots, you need Javascript enabled to view it scattering of long-wavelength photons and large fluorophore Stokes shifts (Zhong et al. 2017).

In vivo fluorescence-based optical imaging provides high spatial and temporal resolution, giving researchers the unique ability to visualize biological processes in real-time (30 frames per second) down to the cellular level (Choi et al. 2013; Hong et al. 2014; Zhu et al. 2017). For decades, one- photon fluorescence imaging in the visible (400-700 nm) and traditional near-infrared (NIR-I; 750-900 nm) regions of the electromagnetic spectrum have been plagued by the inability to clearly resolve deep-tissue structures and physiological dynamics (Hong et al. 2012). As a recent development, NIR-emissive fluorescent probes in the second near-infrared window (NIR- II, 1000-1700 nm) have led to improved in vivo fluorescence imaging quality owing to suppressed scattering of photons and diminished autofluorescence (Welsher et al. 2011; Hong et al. 2014; Zhang et al. 2012). Several classes of fluorescent NIR-II probes have been reported including carbon nanotubes (Hong et al. 2014), conjugated polymers (Tao et al. 2013), small molecular dyes (Antaris et al. 2016) and inorganic-based nanoparticles of quantum dots (Zhang et al. 2012; Tao et al. 2013; Franke et al. 2016), and rare-earth nanocrystals (Naczynski et al. 2013). Indeed, progress has been made in NIR- II in vivo biological imaging owing to the development of various NIR-II fluorescent probes (Sun et al. 2016; Li et al. 2014; Dong et al. 2013). Still, bright probes with emission in the long end of the NIR-II region remain scarce and are desired in order to further reduce scattering of emitted photons arid maximize in vivo fluorescence imaging depth and clarity.

Cancer is one of the most fatal diseases in today's world that kills millions of people every year. It is one of the major health concerns of the 21st century which does not have any boundary and can affect any organ of people from any place (Bharali and Mousa 2010). Cancer, the uncontrolled proliferation of cells where cipoptosis disappears, requires a very complex process of treatment. Because of complexity in genetic and phenotypic levels, it shows clinical diversity and therapeutic resistance. A variety of approaches are being practised for the treatment of cancer each of which has some significant limitations and side effects (Zhao and Rodriguez 2013). Cancer treatment includes surgical removal, chemotherapy, radiation and hormone therapy. Chemotherapy, a very common treatment, delivers anticancer drugs systemically to patients for quenching the uncontrolled proliferation of cancerous cells (Jabir et al. 2012). Unfortunately, due to nonspecific targeting by anticancer agents, many side effects occur and poor drug delivery of those agents cannot bring out the desired outcome in most of the cases. Cancer drug development involves a very complex procedure which is associated with advanced polymer chemistry and electronic engineering. The main challenge of cancer therapeutics is to differentiate the cancerous cells and the normal body cells. That is why the main objective becomes engineering the drug in such a way that it can identify the cancer cells to diminish their growth arid proliferation.

Conventional chemotherapy fails to target the cancerous cells selectively without interacting with the normal body cells. Thus they cause serious

Fig. 7.1. Ce³⁺ doped rare-earth nanoparticles with enhanced NIR-IIb luminescence, (a) Schematic design of a NaYbF₄:Er,Ce@NaYF₄ core-shell nanoparticle (left) with corresponding large scale ТЕМ image (upper right, scale bar = 200 nm) and HRTEM image (lower right, scale bar = 2 nm). (b) Simplified energy-level diagrams depicting the energy transfer between Yb³', Er³', and Ce³⁺ ions, (c) Schematic illustration of the proposed energy-transfer mechanisms in Er-RENPs with and without Ce³~ doping, (d) Upconversion and downconversion luminescence spectra of the Er-RENPs with 0 and 2% Ce³⁺ doping, (e) Schematic representation of Ce³⁺ doping concentration and corresponding upconversion and downconversion emission intensity of the Er- RENPs upon 980 nm excitation (Zhong et al. 2017).

side effects including organ damage resulting in impaired treatment with lower dose and ultimately low survival rates (Mousa and Bharali 2011). Nanotechnology is the science that usually deals with the size range from a few nanometres (nm) to hundred nm, depending on their intended use (Peer et al. 2007). It has been an area of interest over the last decade for developing precise drug delivery systems as it offers numerous benefits to overcome the limitations of conventional formulations (Malam et al. 2009).

Nanoparticles are rapidly being developed and trailed to overcome several limitations of traditional drug delivery systems and are coming up as a distinct therapeutics for cancer treatment. Conventional chemotherapeutics possess some serious side effects including damage of the immune system and other organs with rapidly proliferating cells due to nonspecific targeting, lack of solubility and inability to enter the core of the tumors resulting in impaired treatment with a reduced dose and with low survival rate. Nanotechnology has provided the opportunity to get direct access of the cancerous cells selectively with increased drug localization and cellular uptake. Nanoparticles can be programmed for recognizing the cancerous cells and giving selective and accurate drug delivery avoiding interaction with the healthy cells. This chapter mainly discusses the cell's recognizing ability of nanoparticles by various strategies having unique identifying properties that distinguish them from previous anticancer therapies. It also discusses specific drug delivery by nanoparticles inside the cells illustrating many successful researches and how nanoparticles remove the side effects of conventional therapies with tailored cancer treatment (Sutradhar and Amin 2014).