**3. Near-infrared photothermal ablation**

Near-infrared (NIR) laser light is ideal for *in vivo* hyperthermia applications because of its low absorption by tissue chromophores such as hemoglobin and water. NIR light demonstrates maximal penetration of tissue, thereby reaching deep inside the tissue. Photothermal ablation (PTA) therapy is a recently developed technique that uses NIR laser light-generated heat to destroy tumor cells. In recent years, PTA has gained a lot of popularity mainly because a specific amount of photoenergy is delivered directly into the tumor without causing systemic effects [29]. However, this therapy approach is limited by the fact that the heating is nonspecific and nonuniform mainly in areas peripheral to large blood vessels where heat can be rapidly dissipated by circulating blood.

The efficacy of PTA can be significantly enhanced by using different types of nanoparticles that are applied to the target tissue to mediate selective photothermal effects. For instance, AuNPs including gold nanorods, gold nanocages, gold nanostars, and gold nanopopcorns with unique optical proprieties have been developed [30].

In order to treat a tumor, AuNPs are systemically administered to the subject and allowed to passively localize in the tumor. The tumor is then exposed to an excitation source such as the NIR laser light. The AuNPs absorb the incident energy and convert it into heat, which raises the temperature of the tissue and ablates the cancerous cells by disrupting the cell membrane [31]. AuNPs have unique optical-electronic proprieties as a result of surface plasmon resonances (SPRs). SPR is a phenomenon in which free electrons oscillate collective‐ ly at the interface of metal and surrounding medium in resonance with external electromag‐ netic fields [30].

Nanoparticles in the tissues produce heat strong enough for thermal ablation in both tumors and surrounding cells. Therefore, it is crucial to increase the intratumoral localization of the nanoparticles on the one hand and to protect the surrounding tissue on the other hand. Selective accumulation of AuNPs in the target tumor tissue can be achieved by surface conjugation of targeting agents, such as antibodies and peptides that can recognize specific cell types. For instance Liu et al. reported that gold nanoshells functionalized with the small peptide A54 can significantly increase the efficiency of cancer cell death in the NIR photother‐ mal treatment due to the specific binding (targeting) between the A54-nanoshells and the liver cancer cells, BEL-7404 and BEL-7402 [32].

AuNP can also be functionalized to load various cargoes such as different types of anticancer drugs. As an example in this setting, You et al. investigated DOX-loaded hollow gold nano‐ spheres (DOX@HAuNSs) and conjugated them with a peptide sequence that targets EPHB4, a tyrosine kinase receptor that is often overexpressed in many tumor cell membranes including HCC. NIR laser irradiation after treatment with targeted DOX@HAuNSs resulted in signifi‐ cantly suppressed tumor growth when compared with the control treatment with nontargeted DOX@HAuNSs or HAuNSs [33]. Moreover, another study conducted by the same authors, evaluated the triggered release of paclitaxel via NIR laser irradiation and its antitumor efficacy by hepatic arterial administration of HAuNS and paclitaxel loaded microspheres into rabbits with liver carcinoma in situ [34]. The results showed statistically significant increases in necrosis and apoptosis percentage in the MS-HAuNS-PTX-plus-NIR treatment group com‐ pared with the other two treatment groups.

NPs have been shown to induce cytotoxic effects on themselves and surrounding cells via ROS-

Understanding how nanomaterials affect live cell function, controlling such effects, and using them in therapy (for example In tumor ablation), is now the most challenging aspects of nanobiotechnology. An ideal NP would be a multifunctional one, targeting both the tumor cells and tumor microenvironment with low toxicity, which is easy to engineer, and has low costs. However, there is still a long way and a great deal of research has to be performed in

Near-infrared (NIR) laser light is ideal for *in vivo* hyperthermia applications because of its low absorption by tissue chromophores such as hemoglobin and water. NIR light demonstrates maximal penetration of tissue, thereby reaching deep inside the tissue. Photothermal ablation (PTA) therapy is a recently developed technique that uses NIR laser light-generated heat to destroy tumor cells. In recent years, PTA has gained a lot of popularity mainly because a specific amount of photoenergy is delivered directly into the tumor without causing systemic effects [29]. However, this therapy approach is limited by the fact that the heating is nonspecific and nonuniform mainly in areas peripheral to large blood vessels where heat can be rapidly

The efficacy of PTA can be significantly enhanced by using different types of nanoparticles that are applied to the target tissue to mediate selective photothermal effects. For instance, AuNPs including gold nanorods, gold nanocages, gold nanostars, and gold nanopopcorns

In order to treat a tumor, AuNPs are systemically administered to the subject and allowed to passively localize in the tumor. The tumor is then exposed to an excitation source such as the NIR laser light. The AuNPs absorb the incident energy and convert it into heat, which raises the temperature of the tissue and ablates the cancerous cells by disrupting the cell membrane [31]. AuNPs have unique optical-electronic proprieties as a result of surface plasmon resonances (SPRs). SPR is a phenomenon in which free electrons oscillate collective‐ ly at the interface of metal and surrounding medium in resonance with external electromag‐

Nanoparticles in the tissues produce heat strong enough for thermal ablation in both tumors and surrounding cells. Therefore, it is crucial to increase the intratumoral localization of the nanoparticles on the one hand and to protect the surrounding tissue on the other hand. Selective accumulation of AuNPs in the target tumor tissue can be achieved by surface conjugation of targeting agents, such as antibodies and peptides that can recognize specific cell types. For instance Liu et al. reported that gold nanoshells functionalized with the small peptide A54 can significantly increase the efficiency of cancer cell death in the NIR photother‐ mal treatment due to the specific binding (targeting) between the A54-nanoshells and the liver

mediated activation of the c-jun N-terminal kinase pathway [28].

order to develop what we consider the ideal nanoparticle.

with unique optical proprieties have been developed [30].

**3. Near-infrared photothermal ablation**

dissipated by circulating blood.

228 Recent Advances in Liver Diseases and Surgery

netic fields [30].

cancer cells, BEL-7404 and BEL-7402 [32].

A different approach in the field of NPs, mediated NIR thermal ablation has been developed in the last two years mainly due to the development of therenostic agents, which combine diagnostic and therapeutic modalities. This approach offers tremendous potential for the management of chronic liver injury or HCC. In a recent article, multifunctional nanoprobe based on Glypican-3 anti-body-mediated HCC-targeting Prussian blue nanoparticles (an‐ tiGPR-PBNPs) was developed as a novel theranostic agent for the targeted PTT and MR imaging of HCC treatments [35]. They concluded that antiGPC3-PBNPs could be used as a promising nanoprobe for further treating and early diagnosis of HCC.

A major limitation of nanoparticle-assisted drug delivery is represented by their uptake in the reticuloendothelial system leading to undesirable systemic toxicity and reduced efficacy. Hence many researchers have investigated the use of different cell types for drug delivery. Zhao J et al. in their study used adipose-derived mesenchymal cells (AD-MSCs) to deliver superparamagnetic iron oxide (SPIO)-loaded gold nanoparticles (SPIO@AuNP) into HCC tumors [36]. They demonstrated that AD-MSC is an effective carrier for the specific delivery of theranostic agents to liver injuries or HCC and SPIO@AuNP is a host-compatible cargo that enables both MRI enhancement and laser induced thermal ablation.

Besides the different types of gold nanoparticles described above, carbon nanotubes (CNT) also have the ability to efficiently convert NIR into heat. The role on CNT-mediated thermal therapy for the treatment of a wide variety of cancer types both *in vitro* and *in vivo* have been recently reviewed [37]. It is hard to claim that CNTs are better than GNPs because direct comparisons are hard to make; however, some estimates indicate that CNTs can achieve thermal destruction of tumors at 10-fold-lower doses and a 3-fold-lower power than what is required for gold nanorods [23]. On the other hand GNP can be synthesized with great uniformity and have already been tested in human clinical trials.

It is worth to mentioning that there is a massive amount of research in the field of nanoparticlesmediated PTA therapy. We only provided a few examples that we considered most suitable. Describing all the possible applications of nanoparticles mediated thermal therapy is beyond the purpose of this chapter.
