2.4.3. Gold Nanoparticles/Nanofibers

It is well-known that some non-spherical gold nanoparticles (Au NPs) display large near infrared (NIR) resonances that can be used to induce both hyperthermia and drug delivery when they are irradiated with the appropriate wavelength [97]. As non-invasive therapy, NIR radiation is crucial for biomedical uses because it penetrates tissue more deeply, but it is absorbed less than other types of radiation. NIR hyperthermia is a minimally-invasive oncological treatment strategy in which photon energy is selectively administered and converted into sufficient heat to induce cellular injury [98–100]. An important property concerning Au NPs is that by varying their size and shape, the surface plasmon absorption can be tuned from ultraviolet (UV) to infrared (IR) wavelengths. Recently, the potential uses of gold nanoparticles in NIR-hyperthermia have been reported using a variety of noble metal nanostructures, including gold nanoshells [99,101], gold nanorods [102–104], and recently, gold nanocages [105]. The potential toxic impact of AuNPs has been discussed. The particles size, surface chemistry and the presence of functional groups may play a relevant role in cell toxic effects [106]. Some studies have reported that cationic Au NPs are toxic while anionic AuNPs are non-toxic for cells [107]. The toxicity is caused by the electrostatic interaction of Au NPs with the negatively charged bilayer of the cellular membrane. Several investigations have also confirmed that some modified Au NPs (as PEG-modified Au NPs) are non-toxic at the dose that is effective for in vivo drug delivery [108]. Recently, the synthetic toxicity of AuNPs capped with polyethylenimine (PEI) and PEGylated anisamide has been tested for in vivo investigations, obtaining changes in blood cells by hemocytometer. These results demonstrated nonsignificant differences between hematological toxicity of these modified NPs and controls (saline serum) In addition, an extensive analysis of the tissue injury was carried out using gold nanoparticles prepared with PEG and DOX. In this case, Au3 treatment did not induce histopathologically observable differences in mice (including among others, heart, lung, stomach, intestine, liver, pancreas, kidney, spleen, skeletal muscle, brain, spinal cord) from those treated with saline serum, thus indicating no systemic toxicity [109].

In this context, Zhang et al. [97] incorporated gold nanorods (AuNRs) into pNIPAM NFs in order to create a hybrid composite with fast thermal/optical response and structural integrity by electrospinning. They prepared a mixture of the pNIPAM polymer at 12 wt% and AuNRs in THF, then electrospinning was performed to achieve the hybrid AuNRs-IN-pNIPAM NFs. The photothermal property of these metal nanoparticles and the thermo-responsive property of pNIPAM were demonstrated. They obtained a NFs heating from room temperature to 34.5 ◦C after 1 s of laser application, and a further increase to 60 ◦C in 5 s of irradiation. Figure 8 shows TEM images of both the AuNRs dispersion and the hybrid NFs where the metal nanoparticles are incorporated onto the pNIPAM surface, a photograph of the hybrid composite is also included.

Poly (ε-caprolactone diol) based polyurethane solutions were used to synthesize NFs by electrospinning and they were combined with gold nanoparticles [110]. This nanoformulation was loaded with temolozolamide and was designed as a potential implant that allows a continued release of the antitumor drug for the treatment of glioblastoma multiforme. In fact, in U-87 MG human glioblastoma cell line this nanoformulation achieves a greater cell death overtime in contrast with free temozolamide (25% more) that practically does not modify the percentage of cell proliferation. In the same way as with electrospun NFs made of poly(allylamine hydrochloride) and polyamide 6 covered with MWCNTs, these NFs were also covered with gold nanoparticles for the detection of the pancreatic cancer biomarker CA19-9. In this case, lower biomarker detection thresholds were obtained with the use of gold nanoparticles (1.57 U mL<sup>−</sup>1) compared with the use of MWCNTs (1.84 U mL−1) [79].

**Figure 8.** TEM images of (**A**) Au nanorods (AuNRs), (**B**) AuNRs/PNIPAM electrospun fibers and (**C**) photograph of AuNRs/PNIPAM composite film immersed in water. Reprinted with permission from reference [97]. Copyright ACS Publications, 2017.
