Laser-Induced Heating of Dextran-Coated Mesocapsules Containing Indocyanine Green Mohammad A. Yaseen, † Jie Yu, ‡ Michael S. Wong, ‡ and Bahman Anvari* ,§ Department of Bioengineering, Rice University, MS-142, Houston, Texas 77251, Department of Chemical and Biomolecular Engineering, Rice University, MS-362, Houston, Texas 77251, and Department of Bioengineering, Bourns College of Engineering, University of California, Riverside, California 92521 Indocyanine green (ICG) is a photosensitive reagent with clinically relevant diagnostic and therapeutic applications. Recently, ICG has been investigated for its utility as an exogenous chromophore during laser-induced heating. However, ICG’s effectiveness remains hindered by its molecular instability, rapid circulation kinetics, and nonspecific systemic distribution. To overcome these limitations, we have encapsulated ICG within dextran-coated mesocapsules (MCs). Our objective in this study was to explore the ability of MCs to induce thermal damage in response to laser irradiation. To simulate tumorous tissue targeted with MCs, cylindrical phantoms were prepared consisting of gelatin, intralipid emulsion, and various concentrations of MCs. The phantoms were embedded within fresh chicken breast tissue representing surrounding normal tissue. The tissue models were irradiated at λ ) 808 nm for 10 min at constant power (P ) 4.2 W). Five hypodermic thermocouples were used to record the temperature at various depths below the tissue surface and transverse distances from the laser beam central axis during irradiation. Temperature profiles were processed to remove the baseline temperature and influence of light absorption by the thermocouple and subsequently used to calculate a damage index based on the Arrhenius damage integral. Tissue models containing MCs experienced a maximum temperature change of 18.5 °C. Damage index calculations showed that the heat generation from MCs at these parameters is sufficient to induce thermal damage, while no damage was predicted in the absence of MCs. ICG maintains its heat-generating capabilities in response to NIR laser irradiation when encapsulated within MCs. Such encapsulation provides a potentially useful methodology for laser-induced therapeutic strategies. Introduction Laser-induced thermal injury is a technique aimed at destroy- ing anomalous tissue structures such as tumors or hypervascular lesions. The process relies on the absorption of light to induce temperature rises within the targeted tissue, resulting in necrosis. As is true with all laser-mediated therapeutic strategies, selective laser-induced heating requires substantial absorption of the laser light by the targeted structure with minimal absorption by the surrounding tissues (1, 2). Numerous investigations have demonstrated the ability to destroy tumorous tissue by the introduction of exogenous chromophores such as light-absorbing nanoparticles into the tumor followed by irradiation with a deep penetrating near- infrared (NIR) laser (3-5). In particular, some studies have focused on the use of indocyanine green (ICG) as an exogenous chromophore (6-10). ICG is a tricarbocyanine dye which absorbs and fluoresces in the near-infrared spectral bandwidth of 650-850 nm and is utilized extensively in clinical settings for measurements of cardiac output and plasma volume, imaging choroidal structure, and assessment of liver function (10, 11). ICG’s minimal toxicity and vascular retention have motivated investigations into its utility for a variety of therapeutic applications including photodynamic therapy, tissue welding, and photothermal therapy as well as diagnostic purposes (12- 16). ICG’s utility, however, is limited by its rapid circulation kinetics, inability to be localized, and molecular instability (17). When administered as a bolus injection, ICG binds to plasma proteins in blood and circulates throughout the body. It is also rapidly taken up by liver and excreted to bile (17, 18). After a systemic injection, ICG concentration in blood decreases at a nearly biexponential rate with time constants on the order of 2-4 min (18). The optical properties of IGC also vary considerably with factors such as concentration, solvent, tem- perature, and pH (19-22). In an effort to overcome ICG’s physical limitations, we have formulated charge-assembled capsules with adjustable diameters ranging between 50 nm and 5 μm as a means to encapsulate ICG (23, 24). The capsules containing ICG comprise a polymer-salt aggregate core with a positive surface charge. The core can be coated with a wide variety of negatively charged species, including silica nanoparticles and dextran. Fluorescence images of the capsules reveal that ICG molecules reside within both the capsule’s core and shell (24). In this study, we performed laser-heating experiments using an ICG-capsule system prepared with dextran polymer, with potential for increased biocompatibility and functionalization. The capsule diameters range between 400 and 800 nm, smaller * To whom correspondence should be addressed. E-mail: anvari@ engr.ucr.edu. Tel: 951-827-5726. Fax: 951-827-6416. † Department of Bioengineering, Rice University. ‡ Department of Chemical and Biomolecular Engineering, Rice Univer- sity. § University of California, Riverside. 1431 Biotechnol. Prog. 2007, 23, 1431-1440 10.1021/bp0701618 CCC: $37.00 © 2007 American Chemical Society and American Institute of Chemical Engineers Published on Web 10/03/2007