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Gold nanostructures as a platform for combinational therapy in future cancer therapeutics.

Jelveh S, Chithrani DB - Cancers (Basel) (2011)

Bottom Line: The field of nanotechnology is currently undergoing explosive development on many fronts.In addition, the heat generation capability of gold nanostructures upon exposure to UV or near infrared light is being used to damage tumor cells locally in photothermal therapy.In this review article, the recent progress in the development of gold-based NPs towards improved therapeutics will be discussed.

View Article: PubMed Central - PubMed

Affiliation: Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, Toronto, ON, Canada. devika.chithrani@rmp.uhn.on.ca.

ABSTRACT
The field of nanotechnology is currently undergoing explosive development on many fronts. The technology is expected to generate innovations and play a critical role in cancer therapeutics. Among other nanoparticle (NP) systems, there has been tremendous progress made in the use of spherical gold NPs (GNPs), gold nanorods (GNRs), gold nanoshells (GNSs) and gold nanocages (GNCs) in cancer therapeutics. In treating cancer, radiation therapy and chemotherapy remain the most widely used treatment options and recent developments in cancer research show that the incorporation of gold nanostructures into these protocols has enhanced tumor cell killing. These nanostructures further provide strategies for better loading, targeting, and controlling the release of drugs to minimize the side effects of highly toxic anticancer drugs used in chemotherapy and photodynamic therapy. In addition, the heat generation capability of gold nanostructures upon exposure to UV or near infrared light is being used to damage tumor cells locally in photothermal therapy. Hence, gold nanostructures provide a versatile platform to integrate many therapeutic options leading to effective combinational therapy in the fight against cancer. In this review article, the recent progress in the development of gold-based NPs towards improved therapeutics will be discussed. A multifunctional platform based on gold nanostructures with targeting ligands, therapeutic molecules, and imaging contrast agents, holds an array of promising directions for cancer research.

No MeSH data available.


Related in: MedlinePlus

Mechanisms of radiation induced DNA damage. (a) Absorption of high-energy radiation by water molecules results in formation of H2O+ ions and free electrons. After losing their kinetic energy, the electrons enter a short-lived, prehydrated state. (b) The H2O+ ions react with more water molecules to form protonated water (H3O+) and hydroxyl radicals (OH•). These radicals have long been thought to cause the DNA damage observed in irradiated cells. (c) Prehydrated electrons form complexes with water molecules and turn into hydrated electrons. (d) Prehydrated electrons also react with the bases of certain nucleotides in aqueous solution. This suggests that prehydrated electrons can react with the bases of DNA duplexes, forming transient anions. In some cases, these anions could decompose, breaking molecular bonds in the DNA and so damaging it. Reproduced with permission [33].
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f2-cancers-03-01081: Mechanisms of radiation induced DNA damage. (a) Absorption of high-energy radiation by water molecules results in formation of H2O+ ions and free electrons. After losing their kinetic energy, the electrons enter a short-lived, prehydrated state. (b) The H2O+ ions react with more water molecules to form protonated water (H3O+) and hydroxyl radicals (OH•). These radicals have long been thought to cause the DNA damage observed in irradiated cells. (c) Prehydrated electrons form complexes with water molecules and turn into hydrated electrons. (d) Prehydrated electrons also react with the bases of certain nucleotides in aqueous solution. This suggests that prehydrated electrons can react with the bases of DNA duplexes, forming transient anions. In some cases, these anions could decompose, breaking molecular bonds in the DNA and so damaging it. Reproduced with permission [33].

Mentions: As illustrated in Figure 2, radiation produces ions, radicals and free electrons, as they travel through matter [32-34]. The electrons in turn generate large quantities of a second generation of radicals, ions and free electrons. Most studies suggest that DNA is damaged indirectly by hydroxyl radicals [35]. However, the electrons can also cause damage to DNA, as illustrated in a recent study in which low-energy electrons emitted from metal films were found to cause DNA strand breaks directly [36]. This study was performed using dry films. However, it is important to look at the role of electrons in a biologically relevant environment, such as water. When electrons are generated in water, they become hydrated and form a complex with several water molecules as illustrated in Figure 2. It was assumed that these hydrated electrons do not cause much DNA damage as compared to hydroxyl radicals [33]. Now, the question is whether these hydrated electrons can cause DNA damage. Recently, Wang et al. performed an experiment to study the reaction of prehydrated electrons with deoxyribonucleotides, the building blocks of DNA [37]. The authors performed their experiments in water, which provides a good model for cells. They found that significant quantities of single- and double- strand breaks of irradiated aqueous DNA are induced by prehydrated electrons. Based on these recent studies, both electrons and hydroxyl radicals could be responsible for DNA damage in irradiated cells. In the next section, we will discuss the contribution from GNPs to these existing mechanisms of cell damage after exposure to radiation.


Gold nanostructures as a platform for combinational therapy in future cancer therapeutics.

Jelveh S, Chithrani DB - Cancers (Basel) (2011)

Mechanisms of radiation induced DNA damage. (a) Absorption of high-energy radiation by water molecules results in formation of H2O+ ions and free electrons. After losing their kinetic energy, the electrons enter a short-lived, prehydrated state. (b) The H2O+ ions react with more water molecules to form protonated water (H3O+) and hydroxyl radicals (OH•). These radicals have long been thought to cause the DNA damage observed in irradiated cells. (c) Prehydrated electrons form complexes with water molecules and turn into hydrated electrons. (d) Prehydrated electrons also react with the bases of certain nucleotides in aqueous solution. This suggests that prehydrated electrons can react with the bases of DNA duplexes, forming transient anions. In some cases, these anions could decompose, breaking molecular bonds in the DNA and so damaging it. Reproduced with permission [33].
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3756404&req=5

f2-cancers-03-01081: Mechanisms of radiation induced DNA damage. (a) Absorption of high-energy radiation by water molecules results in formation of H2O+ ions and free electrons. After losing their kinetic energy, the electrons enter a short-lived, prehydrated state. (b) The H2O+ ions react with more water molecules to form protonated water (H3O+) and hydroxyl radicals (OH•). These radicals have long been thought to cause the DNA damage observed in irradiated cells. (c) Prehydrated electrons form complexes with water molecules and turn into hydrated electrons. (d) Prehydrated electrons also react with the bases of certain nucleotides in aqueous solution. This suggests that prehydrated electrons can react with the bases of DNA duplexes, forming transient anions. In some cases, these anions could decompose, breaking molecular bonds in the DNA and so damaging it. Reproduced with permission [33].
Mentions: As illustrated in Figure 2, radiation produces ions, radicals and free electrons, as they travel through matter [32-34]. The electrons in turn generate large quantities of a second generation of radicals, ions and free electrons. Most studies suggest that DNA is damaged indirectly by hydroxyl radicals [35]. However, the electrons can also cause damage to DNA, as illustrated in a recent study in which low-energy electrons emitted from metal films were found to cause DNA strand breaks directly [36]. This study was performed using dry films. However, it is important to look at the role of electrons in a biologically relevant environment, such as water. When electrons are generated in water, they become hydrated and form a complex with several water molecules as illustrated in Figure 2. It was assumed that these hydrated electrons do not cause much DNA damage as compared to hydroxyl radicals [33]. Now, the question is whether these hydrated electrons can cause DNA damage. Recently, Wang et al. performed an experiment to study the reaction of prehydrated electrons with deoxyribonucleotides, the building blocks of DNA [37]. The authors performed their experiments in water, which provides a good model for cells. They found that significant quantities of single- and double- strand breaks of irradiated aqueous DNA are induced by prehydrated electrons. Based on these recent studies, both electrons and hydroxyl radicals could be responsible for DNA damage in irradiated cells. In the next section, we will discuss the contribution from GNPs to these existing mechanisms of cell damage after exposure to radiation.

Bottom Line: The field of nanotechnology is currently undergoing explosive development on many fronts.In addition, the heat generation capability of gold nanostructures upon exposure to UV or near infrared light is being used to damage tumor cells locally in photothermal therapy.In this review article, the recent progress in the development of gold-based NPs towards improved therapeutics will be discussed.

View Article: PubMed Central - PubMed

Affiliation: Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, Toronto, ON, Canada. devika.chithrani@rmp.uhn.on.ca.

ABSTRACT
The field of nanotechnology is currently undergoing explosive development on many fronts. The technology is expected to generate innovations and play a critical role in cancer therapeutics. Among other nanoparticle (NP) systems, there has been tremendous progress made in the use of spherical gold NPs (GNPs), gold nanorods (GNRs), gold nanoshells (GNSs) and gold nanocages (GNCs) in cancer therapeutics. In treating cancer, radiation therapy and chemotherapy remain the most widely used treatment options and recent developments in cancer research show that the incorporation of gold nanostructures into these protocols has enhanced tumor cell killing. These nanostructures further provide strategies for better loading, targeting, and controlling the release of drugs to minimize the side effects of highly toxic anticancer drugs used in chemotherapy and photodynamic therapy. In addition, the heat generation capability of gold nanostructures upon exposure to UV or near infrared light is being used to damage tumor cells locally in photothermal therapy. Hence, gold nanostructures provide a versatile platform to integrate many therapeutic options leading to effective combinational therapy in the fight against cancer. In this review article, the recent progress in the development of gold-based NPs towards improved therapeutics will be discussed. A multifunctional platform based on gold nanostructures with targeting ligands, therapeutic molecules, and imaging contrast agents, holds an array of promising directions for cancer research.

No MeSH data available.


Related in: MedlinePlus