Gold Nanoparticles in Drug Delivery
Gold Nanoparticles in Drug Delivery:
Current cancer therapy strategies are based in surgery, radiotherapy and chemotherapy, being the chemotherapy the one that shows the greater efficiency for cancer treatment, mainly in more advanced stages.. Introduction of new agents to cancer therapy has greatly improved patient survival but still there are several biological barriers that antagonize drug delivery to target cells and tissues, namely unfavourable blood half-life and physiologic behaviour with high off-target effects and effective clearance from the human organism . The development of side effects in normal tissues (e.g. nephrotoxicity, neurotoxicity, cardiotoxicity, etc) and multidrug resistance (MDR) mechanisms by cancer cells leads to a reduction in drug concentration at target location, a poor accumulation in the tumour with consequent reduction of efficacy that may associate to patient relapse.
To overcome these issues and still improve the efficiency of chemotherapeutic agents there is a demand for less toxic and more target specific therapies towards cancer cells, i.e. novel drugs, drug delivery systems (DDSs) and also gene delivery systems. AuNPs appears of great interest in the medical field, great efficiency towards cancer therapy. The continuous interest in AuNPs is based in their tuneable optical properties that can be controlled and modulated for the treatment and diagnosis of diseases. drug delivery to these disease sites and Au nanoparticles further offer a particularly unique set of physical, chemical and photonic properties with which to do so.
Sensing of DNA and Oligonucleotides:
The sensitivity and selectivity response to the biological environment, the optical properties of Au NPs have been used in sensing biological molecules and cells. Various Au NP formulations have been fabricated for targeting biological targets, such as DNA, RNA, cells, metal ions, small organic compounds, protein, and many more of biological specimens. using functionalized Au NPs for biosensing, namely, sensing of DNA and oligonucleotides, SPR biosensor with functionalized Au NPs, cell detection and labeling with functionalized Au NPs, protein detection, detecting heavy metal ions, sensing of glucose, and sensing of other biological-related molecules with functionalized gold nanoparticles, respectively. Detection of DNA, aptamers, and oligonucleotide has received great attention in the past few years because it has important applications in medical research and diagnosis and food and drug industry monitoring. Majority of the assays identify specific sequence through hybridization of an immobilized probe to the target analyte after the latter has been modified with a covalently linked optical probe. Currently, many research teams have developed DNA, aptamers, and oligonucleotide detection schemes that involve the use of chemically functionalized Au NPs . These approaches are simple and straightforward and use facile NPs surface functionalization chemistry and usually do not require expensive instrumentation. In this section, we will discuss a few examples of using functionalized Au NPs as ultrasensitive tools for sensing DNA, aptamers, and oligonucleotides. Many DNAsensing systems have been integrated with Au NPs toenhance the detection limit and sensitivity.
Gold (Au) nanoparticles (AuNPs) exhibit a combination of physical, chemical, optical and electronic properties unique from other biomedical nanotechnologies and provide a highly multifunctional platform with which to image and diagnose diseases, to selectively deliver therapeutic agents to sensitize cells and tissues to treatment regimens, to monitor and guide surgical procedures, and to preferentially administer electromagnetic radiant to disease sites. Owing to their large size, circulating nanoparticles preferentially accumulate at tumour sites and in inflamed tissues due to the characteristically defective architecture of the vessels that supply oxygen and nutrients to these tissue. These platforms can deliver compounds that are intrinsically susceptible to enzymatic degradation, as well as those that exhibit poor intracellular penetration (e.g., siRNA). AuNPs can be routinely surface functionalized with active ligands at densities (1.0 × 106 µm−2) that are 100- and 1000-fold higher than that achievable with conventional liposome’s or poly(lactic-co-glycolic acid) nanoparticles, respectively, allowing their binding affinity to be optimized for a particular disease type, stage or patient. Because of their comparability in size to the distances between cell-surface targets, Au nanostructures can simultaneously engage multiple, adjacent receptor sites, achieving increased selectivity in their uptake through this multivalent avidity.
Applications of colloidal Au nanoparticles in drug delivery and laser photo thermal therapy
AuNPs are particularly attractive for use in multimodal drug-delivery applications where these structures can afford enhanced drug pharmacokinetics/bio distribution and simultaneous hyperthermia and radiation therapy contrast, as well as photo-imaging contrast, spectro chemical diagnostic contrast and, when molecularly directed to specific sub cellular sites, intrinsic pharmacodynamic properties . The ability of these structures to act as photo thermal therapeutic agents arises due to the delocalized nature of their free (conduction) electrons and the increasing polarizability of these charge carriers at the surfaces of these materials. These surface electrons exhibit collective modes of oscillation (surface plasmon modes), which vary in frequency depending on the size/shape of the nanoparticles and its dielectric environment. Plasmon modes that result in a dipolar charge density distribution can couple with and resonantly absorb optical photons of the same frequency, resulting in a transient increase in The local temperature increases attainable using laser photo thermal therapy (PTT) are sufficient to induce rapid tumour cell death (necrosis) with minimal damage to surrounding tissues. The energy of these electrons equivalent to that of the photon (EFermi [Au] ~−5.1 eV v. Evac). AuNPs are comprised of a high atomic number (i.e., high-Z) element, they have been shown to substantially to improve the efficacy of radiotherapy treatments via tumour-localized photoelectron and Auger electron ejection, which can damage the DNA of tumour cells in the local surrounding tissue. Hyperthermia is also known to synergize with radiotherapy treatments; however, reports of multimodal plasmonic laser PTT and high-Z enhanced radiotherapy using AuNPs have yet to be explored.
GOLD NANOPARTICLE-MEDIATED DRUG DELIVERY
Cytotoxicity of gold nanoparticles is inacceptable level as gold nanoparticles are considered to be Gold nanoparticles have the ability of bio-imaging of the effected cancerous cells for therapy. For effective drug delivery system or drug therapy it is important to investigate about the biological effects of the nanoparticles as gold nanoparticles have unique physical and chemical properties and have strong binding attraction for thiols, proteins , carboxylic acid aptamers and disulfides so they have been extensively used in the field of biosciences especially in drug delivery for cancer therapy. Gold nanoparticles followed three main pathways for the cellular uptake which includes receptor mediated endocytosis, phagocytosis and fluidphase endocytosis non-toxic agent. There are two factors, i.e. drug release and transport, which are very important for the efficient drug delivery system. Drugs are loaded on nano carriers by non-covalent interaction or through covalent conjugation with the help of pro-drug, which is treated by the cell. Gold nanoparticles have functional flexibility due to their mono layers so they provide efficient system.
Applications of gold nanoparticles in drug and gene delivery systems
The unique optical, chemical, and biological properties of gold nanoparticles have resulted in them becoming of clinical interest in several applications including drug and gene delivery. The attractive features of gold nanoparticles include their surface Plasmon resonance, the controlled manner in which they interact with thiol groups, and their non-toxic nature in the use of gold nanoparticles in drug and gene delivery systems
New use of dendrimer entrapped gold nanoparticles (Au DENPs) modified with folic acid (FA) as a non-viral vector for targeted gene delivery applications. In this study, amine-terminated generation 5 poly (amidoamine) dendrimers modified with FA via covalent conjugation were used as templates to synthesize gold nanoparticles with an Au salt/dendrimer molar ratio of 25 : 1. The synthesized FA-modified Au DENPs (Au DENPs-FA) were used as a non-viral vector for the delivery of plasmid DNA (pDNA) into a model cancer cell line (HeLa cells) over expressing high-affinity FA receptors (FAR). The DNA compaction ability of the formed Au DENPs-FA was systematically characterized using a gel retardation assay, zeta potential, and dynamic light scattering. We show that similar to the Au DENPs vector without FA, the Au DENPs-FA. was able to compact the pDNA encoding enhanced green fluorescent protein (EGFP). With a lower cytotoxicity than that of the Au DENPs without FA proven by a cell viability assay, the developed FA-modified Au DENPs may be used as a promising non-viral vector for safe and targeted gene therapy applications.
Gold Nanoparticles for Nucleic Acid Delivery
Nucleic acid delivery vehicles are generally divided into two categories: biological and synthetic vectors. On the biological side, viral vectors provide efficient delivery; however, immunogenicity, carcinogenicity, and inflammation can become an issue for clinical applications. Traditional synthetic vectors—including cationic lipids, polymers, and dendrimers have been widely used for intracellular nucleic acid delivery.
Covalent AuNP : The application of RNA interference (RNAi) using AuNPs mainly involves delivery of microRNAs (miRNAs) and small interfering RNAs (siRNAs). Synthesized a class of polyvalent nucleic acid AuNPs (pNA–AuNPs) by functionalizing AuNPs covalently with thiol-modified oligo-nucleotides and applied them to siRNA-based gene silencing. The dense shell of oligo-nucleotides on the surface of these NPs inhibits degradation by nucleases, protecting the payload. Surprisingly, cellular uptake of these pNA–AuNPs was quite rapid with >50 different cell lines, even though their strong negative charge would be expected to prevent uptake (see following text). Cellular uptake of pNA–AuNPs was strongly dependent on the density of the oligo nucleotide on the particle surface, with higher density providing more efficient delivery
Noncovalent AuNP conjugates
Non-covalent nucleic acid delivery vehicles are an attractive alternative to covalent systems. Using supra-molecular conjugates allows the use of unmodified nucleic acids, allowing delivery of DNA for gene therapy and of RNA for knockdown applications. With these systems, the synthetic versatility of the AuNP platform provides multiple options for vehicle design, such as mixed-monolayer-protected AuNPs (MM-AuNPs), amino acid–functionalized AuNPs (AA–AuNPs), and layer-by-layer-fabricated AuNPs (LbL-AuNPs).
The strong negative charge of nucleic acids makes cationic AuNPs obvious partners for self-assembly. In early studies, Rotello et al.created effective delivery vehicles for plasmid DNA using quaternary ammonium–functionalized AuNPs
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