# Gold Nanoparticles for Drug Delivery and Cancer Therapy
## 4 Gold Nanoparticle-Based Drug Delivery
### Plasmid Deoxynucleic Acids Vector (pDNAAs) Delivery  
DNA-functionalized Au NPs are widely used in biosensors and drug delivery. The DNA Au NP conjugate can affect DNA absorption and the function of the attached protein corona on the NP [74]. Polyvalent DNA-Au NP conjugate has been an efficient and universal nano-carrier for drug and gene delivery, used in over 50 types of primary and cancer cell lines in the past 10 years. The interaction with blood serum content and nuclease degradation are the two primary barriers that limit the effectiveness of the DNA-Au NP conjugate. Terminal PEGylation of the complementary DNA strand hybridized to a polyvalent DNA-Au NP conjugate can eliminate the nonspecific absorption of serum proteins and increase its resistance against DNase I-based degradation. This increases the efficiency while maintaining a high cellular uptake [75]. For recent studies in the functionalization of Au NPs with thiol-modification, oligonucleotides have made the design of sophisticated NPs and nanostructures. Oligonucleotides are considered superior ligands due to their biomedical relevance, versatility, selectivity, high specificity and ease of chemical manipulation. Oligonucleotide functionalized Au NPs have been used to create NP dimers, trimers and tetramers that have adjustable NP distances and mesoscale structures, which contain millions of NPs in a precise pattern. DNA materials can be bound to the Au NPs with covalent linkage, which enhances their stability under DNA denaturingconditions. Synthetic oligonucleotides can be modified by an azide or alkyne group when brought in proximity using a templating splint strand. Partial complementarity to modified oligonucleotides causes oligonucleotide hybridization and eventually catalyzes a ligation reaction. This method was used to create Au NP dimers and trimers with a high production rate and was stable in DNA denaturing condition. These dimers have multiplexed synergistic function in a cellular environment. They can be directed to two mRNA targets, and simultaneously or independently deliver one or two anticancer drugs to the living cells [76]. For therapeutic purposes to deliver nucleic acids efficiently, we need delivery systems that can compact genetic materials and maintain structural integrity when overcoming different delivery barriers, which must unload the genetic material to the target. Au NPs are often coated with amphiphiles to better transport DNA materials. A study was conducted to observe the delivery of plasmid DNA (pDNA) using Au NP coated with pyridinium amphiphiles (SPYRIT-68). The shape and size of the NP impacted the cell and its uptake. A very high curvature can produce a higher cytotoxic profile through the membrane portion. The size and shape of the Au NPs also control the blending of NP to bilayer forming cation lipids such as Ole, which generally has a cylindrical structure. For this experiment, small Au NPs (20 nm) with typical curvature were used. The Au NPs were stabilized using amphiphilic triethylenedylocal mercaptan. Positively charged Au NPs were used for DNA compaction and Ole alone could fully compact the DNA at a +35 mV. This synergistic compaction effect of Au NPs and Ole allows a decrease in charge ratio, while still providing a good compaction of pDNA [77]. DNA delivery encapsulated in Au NPs in nanogels has been introduced and showed improved results. Polymeric NPs, such as in a nanogel, is a versatile delivery system that can encapsulate and release various biomolecules in controllable ways, prohibit metal NP aggregation, and reduce cytotoxicity. The reaction parameters of Poly(N-isopropylacrylamide)--such as concentration of the monomer and initiator, medium polarity and polymerization temperature--were investigated for biomedical and bioengineering applications [78]. In a study, a poly(N-isopropylacrylamide)-based nanogel was used as a template for Au NPs due to biocompatibility, and properties such as easy modification and thermo-responsiveness.