Send Orders for Reprints to reprints@benthamscience.net 6622 Current Pharmaceutical Design, 2013, 19, 6622-6634 Nanomaterials for Photohyperthermia: A Review Jonathan Fang and Yu-Chie Chen* Department of Applied Chemistry, National Chiao Tung University, Hsinchu 300, Taiwan Abstract: The unique properties of nanomaterials have propelled the field of nanomedicine. Nanomaterials have been used as drug de- livery, imaging, and photothermal agents for diagnosis and therapy of diseases. Recently, photohyperthermia has attracted great interest from researchers and is actively being investigated as an alternative method of therapy for cancer and even bacteria. Photohyperthermia, or photothermal therapy, is the process of a photothermal agent absorbing light and converting it into heat for the destruction of malig- nant cells, which is due to elevated temperatures. This technique is non-invasive, can target specific diseased cells for minimal adverse side effects, and can be used in conjunction with other cancer treatments, such as chemotherapy. In this review, we will discuss different nanomaterials that have been implemented as photothermal agents for the treatment of various cancer and bacterial cells. The review will mainly focus on gold nanoparticles, magnetic nanoparticles, and carbon nanotubes. However, other nanomaterials, such as semiconductor nanoparticles and polymer composites, will be briefly discussed. In addition, the photothermal mechanism, current developments, dual imaging and therapy, and future perspectives of nanoparticle-based photohyperthermia will be presented. Keywords: Nanomaterials, photohyperthermia, photothermal agents, gold nanoparticles, magnetic nanoparticles, carbon nanotubes, theranos- tics. 1. INTRODUCTION The advent of nanotechnology has had a tremendous impact on many areas in science and engineering, especially in biotechnology and health care. Nanomaterials have greatly advanced the field of nanomedicine and have recently been used in areas such as drug delivery, imaging [1], cell targeting [2], and photothermal therapy [1, 2]. There are a wide variety of drug carriers that have been used for the delivery of therapeutic agents. Specifically, biodegradable polymeric nanoparticles [3-6] are a promising group of organic compounds that have been researched and utilized for drug delivery applications due to properties such as excellent biocompatibility and controlled, stimuli-responsive release capabilities. One class of these polymeric nanoparticles is polyesters [3], such as poly(lactic acid) (PLA) [4], poly(lactide-co-glycolide) (PLGA) [5], and poly(- caprolactone) (PCL) [6], which have been used for the delivery of anti-cancer therapeutic agents [3-6]. In addition, non-polymeric nano-scale drug carriers, such as liposomes, have been used for the delivery of anti-HIV drugs [7]. These materials are excellent drug carriers due to their established biocompatibility and their ability to enhance drug bioavailability. Other nanomaterials that have been used for drug delivery are inorganic nanoparticles, such as silica nanoparticles [8, 9]. In contrast to drug delivery, photohyperthermia is an alternative therapeutic method that has recently attracted re- searchers and been investigated for the treatment of cancer and other infectious diseases. This technique relies on the use of pho- tothermal agents that can convert light energy into heat for the pur- pose of destroying malignant cells. In this review, we will provide an overview on the nanomaterials that have been implemented as photothermal agents for photohyperthermia. 2. PHOTOHYPERTHERMIA Hyperthermia is the procedure of heating a region in the body affected by cancer or other diseases and killing the malignant cells, which is typically achieved when the temperature is raised to be- tween 40°C and 44°C [10-12]. It is a therapeutic method that has been gaining interest due to its generally low toxicity [12], non- invasiveness, simplicity [13], and potential to treat tumors in areas *Address correspondence to this author at the Department of Applied Chemistry, National Chiao Tung University, Hsinchu 300, Taiwan; Tel: +886-3-5131527; Fax: +886-3-5723764; E-mail: yuchie@mail.nctu.edu.tw where surgical resection may not be viable [14]. The rationale for this type of treatment is based on the observation that direct cell- killing of tumors occurs at or above temperatures between 41°C and 42°C [11, 15-17]. Tumors are more susceptible to heat than healthy cells, making hyperthermia a viable treatment option [10]. Cell death from hyperthermia can be caused by several mechanisms, such as degradation of the cell wall membrane [13, 16], protein denaturation [13], and the production of reactive oxygen species, leading to necrosis and apoptosis [18]. Hyperthermia has been combined with chemotherapy [11, 15, 17, 19] and radiotherapy [17, 20, 21] for enhanced treatment of many different types of cancer. Multimodal cancer treatments have increased response rates and patient survival [17]. The types of cancers that have been treated with hyperthermia include melanoma, head and neck, esophageal [12], liver [14], cervical [21], breast [22], prostate [23], rectal [24], and ovarian cancer [25]. Hyperthermia has even been used to treat bone tumors [26] and patients with human immunodeficiency virus [27]. Energy sources that have been used for hyperthermia include magnetic fields [22], lasers [28], radiofrequency (RF) pulses [29], and ultrasound [30]. There have been plenty of reviews that have covered clinical hyperthermia, such as those by van der Zee [10], Wust et al. [11], Falk and Issels [12], and Christophi et al. [16]. In addition, cancer treatments that combine hyperthermia with chemo- therapy (Takahashi et al. [19]) and radiotherapy (Horsman and Overgaard [20]) have been reviewed. Research on photohyperthermia, or photothermal therapy, for the treatment of cancer and bacteria has been recently gaining mo- mentum. Photothermal therapy is the process of converting light energy into heat for the purpose of damaging and destroying dis- eased cells, such as cancer and bacteria. Surface plasmon resonance (SPR) can be described as resonant oscillations of free electrons of a particle irradiated by light [31]. When a photothermal agent, such as a gold nanoparticle, strongly absorbs incident light near its SPR peak, conduction band electrons decay to the ground state and re- leases heat in the process [32, 33]. The photothermal process is similar to that of another treatment method, photodynamic therapy (PDT), except that PDT undergoes photochemical processes that produce singlet oxygen, which introduces concerns over tissue oxy- genation and cytotoxicity [2, 34, 35]. The majority of studies in- volving photothermal therapy have focused on treating or destroy- ing various cancer cells, with some emphasis on killing bacteria. Photohyperthermia is rapidly emerging as an alternative to conven- 1873-4286/13 $58.00+.00 © 2013 Bentham Science Publishers