Plasmonic photothermal therapy (PPTT) using gold nanoparticles

Title: Plasmonic photothermal therapy (PPTT) using gold nanoparticles

Authors: Xiaohua Huang, Prashant K. Jain, Ivan H. El-Sayed, Mostafa A. El-Sayed

By: Ehsan Moaseri – Behzad Changalvaie

 

Cancer therapeutics have been a principal part of biomedical research in the past two decades. A significant portion of this research has been aimed towards destruction of tumors by using light as a potential heat source. Different modalities, such as photodynamic therapy and photothermal therapy, have emerged as effective methods for tumor destruction. The presented article gives an overview of photothermal therapy and introduces plasmonic photothermal therapy, a subcategory of photothermal therapy using noble metals.

To understand tumor therapy methods, it is crucial to understand how tumors are destroyed. Due to their poor blood supply, tumors have a low heat tolerance compared to normal tissues. Heating tissues to temperatures ranging from 41-48˚C, and staying in this range for an extended period of time will damage the tumors irreversibly (this is known as hyperthermia). However, using traditional heating sources (radio, micro, and ultrasound waves) is not desirable, because these sources target and damage the surrounding healthy tissues as well. Thus, to avoid harming the healthy tissues, a heat source with improved precision and effective area is needed.

Laser provides a very narrow, intense beam that transmits deep into the target issue with great precision. However, laser therapy is not selective; meaning that both normal and tumor cells in the path of laser will be damaged. Laser also requires a high power density for tumor destruction.

To account for the non-selectivity of laser light, photothermal therapy (PTT) was developed. In this method, chemical agents enable selective heating only in locations where the chemical agents accumulate. It should be noted that these agents would preferentially accumulate in the tumor cells due to their poor blood circulation. The agents are able to absorb light and transform the energy from light into kinetic energy. The increase in kinetic energy will result in overheating of the local environment, which will lead to cell or tissue destruction. Historically, natural chromophores (atoms responsible for color) or externally added organic dyes have been used for PTT. However, chromophores have very low light absorption compared to dyes or metallic nanoparticles; and dye molecules photobleach (lose color) under laser irradiation.

This is where nanotechnology comes into play in this treatment technique. In recent years, noble metal nanostructures with unique optical properties have been created for biomedical applications. These nanostructures do not suffer from photo-bleaching and have up to five times higher absorption cross sections compared to photoabsorbing dyes. This high absorption results in a lower laser energy requirement. Great candidates for photothermal therapy include gold nanospheres, nanorods, and nanoshells; as they show strongly enhanced absorption in the 400-1000nm wavelength region, are easy to prepare, and have tunable optical properties. The use of plasmonic nanostructures for photothermal therapy has been categorized as “plasmonic photothermal theraphy” (PPTT).

It is useful to know why plasmonic nanostructures make suitable candidates for photothermal therapy. Regarding light absorption, gold nanoparticles absorb light strongly in the visible region due to the coherent oscillations of the conduction band electrons in strong resonance with visible frequencies of light. The mechanism in which light is transformed into heat is somewhat different than those of photothermal dyes. For metal nanoparticles, upon light irradiation, a heated electron gas is formed that rapidly cools by exchanging heat with the nanoparticle lattice. In turn, the nanoparticle lattice exchanges energy with the surrounding medium. This fast energy exchange causes a highly-efficient heating in the local environment. This local heating causes irreversible cell destruction through protein desaturation and membrane destruction. In addition, the laser power density needed for tumor destruction is several orders of magnitude lower than other phothermal therapy agents.

Noble metal nanoparticles show great potential for photothermal therapy. However, a number of issues regarding these nanoparticles have to be addressed. Their stability in physiological environments, biocompatibility, blood retention time, and their fate following therapy remain to be topics of interest in research related to cancer therapy and imaging. El-Sayed group have published many other papers related to cancer therapy, which can be helpful reads for an in-depth understanding of cancer therapeutics.

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