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Application of Quantum Dots Theranostics Agents

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Table of Contents

  • Introduction
  • Pharmacokinetics, And Pharmacodynamics Of Theranostic Nanomaterials
  • Applications in drug delivery
  • Photodynamic therapy
  • Magnetic hyperthermia

Introduction

Quantum dots are tiny particles or nanocrystals of a semiconducting materials with diameters in the range of 2-10 nanometer (10-50 atoms). As result of this phenomenon, quantum dots can emit any color of the light from the same materials simply by changing the dots sized. Currently, nanoparticles, is the part of nanotechnology products, that are produced in worldwide. Nanoparticles have become worldwide used in area ranging from physics to biology due to their unique properties.

In the fields of nanotechnology, nanoparticles are usually categories into five which are carbon nanotubes (CNTs) and fullerenes, metals, ceramics, polymeric and semiconductors [known as quantum dots (QDs)]1. (The reasons of QDs becoming an importances class of nanoparticles are their photophysical and electrical properties that have great potential values in energy and healths applications. Quantum dots are nanometer-scale crystalline semiconductors consisting of chemical elements from Groups III–IV or Groups II–VI of the periodic table. Sizes of QDs diameter are close to or less than Exciton Bohr radius, and typical ones range from roughly (2–10 nm) (Leutwyler et al. , 1996).

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A typical QDs is composed of one kind of semiconductor material as core packaged with another kind of semiconductor material as shell. Sometimes, QDs need to be solubilization or biological interfacing for special biomedical applications. Thus, a large number of surface attachment materials, mostly biomolecules, need to be conjugated to QDs, such as peptides, antibodies and oligonucleotides (DNA or RNA) (Michalet et al. , 2005). Cancer is the uncontrolled growth of abnormal cells in the body. Cancer develops when the body is normal control mechanism stops working. Cancer is the second causative agents of death With an estimation of 1,658,370 new cases and 589,430 deaths in the United States in 2015, and 1600 deaths per day [1 Despite advances in management, treatment, diagnosis, and prevention options, cancer mortality rates, however, have only dropped 1. 6 %. These statistics indicate that there is a pressing need to develop novel treatments and approaches that will increase the survival rates.

Pharmacokinetics, And Pharmacodynamics Of Theranostic Nanomaterials

Pharmacodynamics of theranostic nanomaterials Sche matic illustration of a multifunctional nanocompositeThe therapeutic or medicinal effectiveness of any theranostics can be determining by the action of medicinal nanomaterials only. Usually, the nanomaterials are stimulant responsive (such as pH, magnetic field, light) and thus act spontaneously upon stimulation, however, the therapeutic can act only after being released from the carrier and reach the target site. For instance, gold nanostructures accumulated in the tumor region can be easily illiminate by near-infrared (NIR) light eading to spontaneous generation of heat and resulting in cancer cell death via hyperthermia.

On the other side, encapsulated anticancer drug molecules [doxorubicin (DOX)] can only execute cancer cell killing after their delivery by nanomaterial carrier, accumulation, migration to the cancerous cells, and finally release from nanodelivery vehicle. Hence, it is important to understand the therapeutic behaviors of nanomaterials in terms of the action mechanisms to studies PK characteristics of anomaterial-based management/ therapy. In addition, various other factors also complicate the explanation for the mechanism of herapeutic action of the nanomaterials such as toxicity, easy removal of conventional drugs from the body or liver metabolic pathways, nanomaterials accumulation not only at the target site but also in undesired organs such as liver. Therapeutic strategies used in theranostic applications.

Drug delivery. Efficient drug delivery is importent therapeutic strategy aquired in the design of a nanotheranostic agent. Anticancer Dugs as such Mephalan, Doxorubicin, vincristine, Topoteca, Cisplatin, Chlorambucil, Carmustine, Lomustine, 5Fluorouracil etc are conjugated or entrapped with the theranostic nanoparticles to accomplish the desired therapeutic response Singh et al. , 2009). These theranostic nanoparticles by virtue of its enhanced permeability and retention effect accumulates on the tumor tissues and releases the loaded drug in a slow and sustainable manner (Fang et al. , 2011). The properties of theranostic agents such as surface charge, size, biodegradability and hydrophobicity are tailored to get the optimal therapeutic response (Moghimi et al. , 2001), (Panyam et al. , 2003), (Panyam et al. , 2003). The nanosize of these carriers favors good cellular uptake and targeted distribution of drugs. Non-targeted distributions of anticancer drugs are one of the major concerns in cancer therapy. Thesenanotheranostic agents can be incorporated with stimuli responsive units. Different types of stimuli responsive strategy are investigated for drug delivery.

Applications in drug delivery

Drug loading strategy Is the essential features of a desirable drugs delivery platform include controllable size, easy surface modification, excellent biocompatibility, low toxicity, high stability and sufficient biosafety in biological systems. pH responsive drug delivery pH is one of the most important stimuli used for drug delivery applications. There is a natural existence of pH gradient inside the body among different organs and tissues such as stomach lumen (pH 1-3), duodenum and ileum (pH 6. 6-7. 5), normal tissues (7. 4) and tumor tissues (5. 7-7. 8) (Gao et al. , 2010), (Rajput et al. , 2010), (Davis et al. , 1993).

The acidic environment around the tumor tissues can be attributed to high levels of production of lactic acid owing to increased rate of glucose uptake by tumor cells. This effect is termed as Warburg’s effect (Kim. , 2006). Hence this natural existence of pH difference among different organs and tissues can be exploited for the construction of smart responsive drug reservoirs. They act as programmable drug delivery vehicles where the release of the loaded drug can be controlled by the external pH (Asokan et al. , 2002), (Vaupel et al. , 2004), (Gerweck et al. , 2006). The pH sensitivity can be imparted to a nanocarrier by the incorporation of pH sensitive groups such as carboxylic acid or amino acid on the structural units of these nanocarriers. pH sensitivity arises due to the ionization of these pendant carboxylic acid or amino acid groups present in the carrier with pKa values ranging from 3-11. Depending on the type of drug delivery, pH sensitivity can be tuned such as for tumor therapy. Usually the protonating amino groups in the nanocarriers undergo ionization and induce subsequent release of the loaded drug upon reaching the tumor site (lower pH) (Schmalijohann et al. , 2006). On the other hand for drug delivery applications such as acidic environments of stomach.

Photodynamic therapy

Photodynamic therapy is an emerging therapeutic modality used for cancer management and treatment. Unlike the conventional chemotherapy which has more systemic side effects, photodynamic therapy offers several advantages such as minimum invasiveness, repeatability without cumulative toxicity and effective ablation of tumor cells without injure the surrounding normal cells (Lucky et al. , 2015). Photodynamic therapy was first demonstrated by Dougherty etal in 1975 (Dougherty et al. , 1975); afterwards much important advancement has taken place to increase the efficacy of this treatment modality. The primary action mechanism of photodynamic therapy involves the administration of a photosenisitizer into the tumor site followed by the irradiation of the tumor site with light having specific wavelength. This irradiation of light excites the photosensitizer to excited singlet state and generates cytotoxic reactive oxygen species which can lead to cancer cell ablation (Castano et al. , 2005).

The tumor cell destruction capability of photodynamic therapy depends on several factors such as concentration of the administrated photosensitizer, the type of tumor and the level of oxygenation produced after light irradiating.

Magnetic hyperthermia

Magnetic hyperthermia is a treatment modality widely used to destroy cancer cells. Even though the major intention of magnetic hyperthermia is to kill cancer cells, it is also used to make cancer cells more sensitive to radiation and certain anticancer drugs (Banobre et al. , 2013), (Chichel et al. , 2007). Magnetic hyperthermia uses electromagnetic radiation in radiofrequency region which is safer and ensures high penetration to inner organs and tissues.

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