Naturally Derived Carbon Dots as Bioimaging Agents

*Gangaraju Gedda, Arun Bhupathi and V.L.N. Balaji Gupta Tiruveedhi*

## **Abstract**

The recent advances in nanoscience and technology have opened new avenues for carbon-based nanomaterials. Especially, Carbon dots (CDs) have gained significant attention due to their simple, economic and rapid green synthesis. These materials exhibit excellent water solubility, fluorescence emission, high fluorescence quantum yield, Ultraviolet (UV) to Infrared (IR) range absorbance and high bio-compatibility. Therefore, these materials are widely used for various biological applications including bio-imaging. With the integration and doping of surface passive agents and elements, respectively influenced the enhancement of fluorescence property of CDs. Also, the conjugation of receptor-based targeting ligands leads to targeted bioimaging. CDs in combination with other imaging contrast agents lead to the development of novel contrast agents for bimodal imaging and multimodal imaging techniques. The combination of diagnostic CDs with therapeutic agents resulted in the formation of theragnostic CDs for image guided therapies. In this chapter, a comprehensive view on the top-down and bottom–up green synthesis methods for naturally derived CDs discussed. Further, unique physical, chemical, optical and biological properties of CDs described. Finally, fluorescence based bimodal and multimodal imaging techniques also described.

**Keywords:** carbon dot, bioimaging, fluorescence, theragnostic, contrast agent

### **1. Introduction**

The term 'imaging' is a perception that it is a type of photography; however, it is far from the biomedical domain. Bioimaging provides the anatomical visualization of cellular, subcellular structures, tissues, organs of multicellular organisms [1]. The biomedical imaging modalities utilize the various kind of energy sources such as light, magnetic resonance, positrons, ultrasound, electrons, and X-rays. The broad range of medical imaging modalities includes fluorescence (FL); X-ray computed tomography (CT), magnetic resonance (MR), ultrasound (US), positron emission tomography (PET) and single-photon emission computed tomography (SPECT) for diagnosis of various soft tissues and hard tissue pathologies and scientific research [2]. These techniques disclose the three-dimensional molecular information of any specimen's biological structures and physiological processes.

Optical imaging, predominantly FL imaging modality received special attention from all the imaging modalities due to their simple operation process, cost-effective armamentarium, excellent resolution, incredible sensitivity and high resolution [3–5]. Therefore, a wide range of fluorescent imaging probes has been discovered for FL imaging, such as organic dyes, semiconductor quantum dots, metal nanocluster and up-conversion nanoparticles [3, 4, 6]. Nevertheless, their limitations include high toxicity, complicated synthesis mechanisms, poor water-solubility and high cost. On the other hand, single-mode fluorescence imaging techniques were limited to depth penetration and difficulty to provide tomographic information due to light attenuation and photon scattering of biological tissue. Therefore, developing FL based multimodal imaging by integrating other imaging modalities with FL imaging modality has become an essential strategy to resolve the single mode FL imaging limitations. Interestingly, FL based multimodal imaging provides several advantages including non-invasive imaging visualization with superior depth penetration, higher sensitivity and resolution [7]. Hence, it is necessary to develop a single probe by integrating other contrast agents with fluorescent materials for FL-based multimodality imaging applications.

Nanotechnology advancements in contrast agent development are progressing rapidly either by doping/incorporating or conjugation of other contrast elements into/with fluorescent nanomaterials to obtain a multimodal imaging probe [8]. Among the various types of nanomaterials, carbon dots (CDs) gained remarkable attention due to their significant physical, chemical and biological properties [9]. The integration of several unique properties in single nanosize carbon dots (CDs), make them ideal alternative material to replace the semiconductor quantum dots, metallic nanomaterials and other forms of carbon materials in various fields. Specifically, bioimaging, drug delivery, phototherapy, anti-microbial agents, sensors, solar cells, light-emitting diodes and photocatalysis [10–13]. Specifically, CDs show significant potential in fluorescence-based multimodal imaging *in vivo* and *in vitro*. For example, FL/MR dual-modal imaging was developed by integrating iron oxide nanomaterials or doping Gd3+ or Mn2+ ions into CDs. Similarly, FL/PA, FL/CT and FL/PET etc., established by incorporating respective contrast agents. This book chapter initially discusses the top-down, bottom-up and green synthesis procedures of CDs, optical properties, and elemental doping and surface functionalization. Next, the bioimaging, importance of carbon dots application in the various medical imaging techniques, and therapeutic applications of carbon dots together as theragnostic are described. Finally, the outlook of carbon dots in bioimaging is mentioned.
