Photothermal Sensitizers Research Articles

Photothermal ablation therapy for cancer based on metal nanostructures

Besides conventional surgery, radiation therapy, and chemotherapy, which all tend to have side-effects and damage normal tissues, new medical strategies, such as photothermal sensitization and photothermal ablation therapy (PTA) with near-IR laser light, have been explored for treating cancer. Much of the current excitement surrounding nanoscience is directly connected to the promise of new nanotechnology for cancer diagnosis and therapy. The basic principle behind PTA is that heat generated from light can be used to destroy cancer cells. Strong optical absorption and high efficiency of photothermal conversion at the cancer sites are critical to the success of PTA. Because of their unique optical properties, e.g., strong surface plasmon resonance (SPR) absorption, noble metal nanomaterials, such as gold and silver, have been found to significantly enhance photothermal conversion for PTA applications. Substantial effort has been made to develop metal nanostructures with optimal structural and photothermal properties. Ideal metal nanostructures should have strong and tunable SPR, be easy to deliver, have low toxicity, and be convenient for bioconjugation for actively targeting specific cancer cells. This review would highlight some gold nanostructures with various shapes and properties, including nanoparticles (NPs), nanorods (NRs), nanoshells, nanocages, and hollow nanospheres, which have been studied for PTA applications. Among these structures, hollow gold nanospheres (HGNs) exhibit arguably the best combined properties because of their small size (30–50 nm), spherical shape, and strong, narrow, and tunable SPR absorption.

Photophysical Behavior of Open-Shell First-Row Transition-Metal Octabutoxynaphthalocyanines: CoNc(OBu)8 and CuNc(OBu)8 as Case Studies

Ultrafast photodynamics and density functional theory/time-dependent density functional theory (DFT/TDDFT) results for complexes of Co and Cu with 5,9,14,18,23,27,32,36-octabutoxynaphthalocyanine [CoNc(OBu)8 and CuNc(OBu)8] are reported. As a basis for this work, details concerning the syntheses of these complexes and the corresponding Zn complex (used as a reference) are given. Transient absorption spectrometry with femtosecond time resolution combined with a detailed DFT/TDDFT analysis has been employed to construct a complete picture of the excited-state dynamics after Q-band excitation of the Co and Cu complexes and to gain an understanding of the relationship between the nature of the metal center and the excited-state lifetime. The Co complex was shown to return to its ground state via two competing channels: a (2)T1(pi, pi*) state that decayed with a lifetime of 1 ps and a low-lying (2)(d, d) state that repopulated the ground-state surface with a lifetime of 15 ps. CuNc(OBu)8 showed ground-state repopulation from the (2)T1(pi, pi*) state via a lower-lying ligand-to-metal charge-transfer (LMCT) state that was completed within a few nanoseconds. The photophysical behavior of the cobalt and copper complexes was compared to that previously reported for the nickel analog in an effort to highlight the effect of the central metal on the nature and rates of the deactivation pathways. The results described in this work provide basic knowledge that is relevant to the use of these compounds as photothermal sensitizers in cancer therapy.

On the photophysics of metallophthalocyanine-based photothermal sensitizers: Synergism between theory and experiment

A comprehensive understanding of the factors governing the efficiency of metallophthalocyanine-based photothermal sensitizers requires the knowledge of their excited-state dynamics. This can only be properly gained when the nature and energy of the excited states (often spectroscopically silent) lying between the photogenerated state and the ground state are known. Here the excited state deactivation mechanism of two very promising metallophthalocyanine-based photothermal sensitizers, NiPc(OBu) 8 and NiNc(OBu) 8, is reviewed. It is shown that time dependent density functional theory (TDDFT) methods are capable to provide reliable information on the nature and energies of the low-lying excited states along the relaxation pathways. TDDFT calculations and ultrafast experiments consistently show that benzoannulation of the Pc ring modifies the photodeactivation mechanism of the photogenerated S 1(π, π ∗) state by inducing substantial changes in the relative energies of the excited states lying between the S 1(π, π ∗) state and the ground state.

Photothermal sensitisation: evidence for the lack of oxygen effect on the photosensitising activity

Irradiation of amelanotic melanoma B78H1 cells in the presence of liposome-delivered Ni(II)-octabutoxy-naphthalocyanine with a Q-switched Ti:sapphire laser operated in a pulsed mode (850 nm, 30 ns pulses, 10 Hz, 120 mJ pulse -1) promotes a photothermal sensitization process leading to extensive cell inactivation. The photoprocess occurs with identical efficiency in N2-saturated and air-equilibrated media, indicating that this photosensitization modality does not require the presence of oxygen.

Deposition of thin polytetrafluoroethylene (PTFE) films using fundamental pulses of a Nd3+: YAG laser

Pulsed laser deposition of PTFE was carried out using a 1064-nm laser. Two different pulse regimes were examined to determine their effectiveness in causing deposition. The first of these consisted of a 20-ns Gaussian pulse, while the second was a pulse train comprising twenty 1-μs pulses with a total duration time of 100-μs. The main feature of the deposition technique that we present in this work is that ablation is induced by the efficient photothermal sensitization of graphite particles that are used to lightly dope (0.1 wt. %) a PTFE target. Both of the pulse regimes produced thin films whose infrared spectra were similar to that of PTFE. For the ns-pulse, however, carbon particles were contained in the deposited films. This behavior can be easily interpreted within the framework of photothermal ablation. For the μs pulse train, homogeneous heating is achieved due to the long thermal diffusion length, which is comparable to the average distance between the graphite particles used to dope the PTFE target. The thin PTFE films are deposited mainly by the mechanism of monomer re-polymerization. The present study demonstrates that near-infrared lasers of the μs-pulse type, which are versatile, economical and widely used in industry, are capable of the deposition of PTFE.

Comparison of the photothermal sensitivity of an interferometric optical fiber probe with pulsed photothermal radiometry

An interferometric optical fiber probe for making photothermal measurements of tissue optical and thermal properties is compared to pulsed photothermal radiometry in terms of its overall thermal sensitivity, linearity, and response time. The principles of operation of the probe are described and its performance as a low finesse Fabry–Perot interferometer is discussed. A probe with a 12 μm sensing film is characterized by a thermal noise floor of 50 mK and a response time of 850 μs. The sensitivities to the optical and thermal coefficients of the two techniques have been analyzed. As a result of the different source geometries, the optical fiber probe was found to be more sensitive to the thermal coefficients of tissue than the optical coefficients while pulsed photothermal radiometry provided maximum sensitivity to the optical coefficients.

Quantitative photothermal characterization of ion-implanted layers in Si

Quantitative analysis of ion-implanted layers in Si using the damage-based theoretical modeling and experimental results obtained with the photomodulated reflectance (PMR) technique are described. Our theoretical approach combines the conventional quantum mechanics based calculations of the ion-induced damage depth profiles in semiconductors with the corresponding scaling of the thermal and carrier plasma parameters followed by the calculation of the photothermal response from a multilayered sample. The theoretical limit of the photothermal signal sensitivity to the implantation dose in the absence of optical and carrier plasma-wave interference effects is estimated. Simulations of the photothermal amplitude and phase dose dependencies allow us to follow the dynamics of the thermal- and carrier plasma waves in an ion-implanted semiconductor. The validity of the proposed damage-based modeling approach to the problem of quantitative analysis of surface-modified semiconductors is analyzed. It is shown that the results of the photothermal damage-based modeling are in a very good agreement with experimentally observed PMR signal implantation dose behavior for B+-implanted Si across the entire range of practically important implantation doses: 109–1015 cm−2.

Photothermal sensitization of amelanotic melanoma cells by Ni(II)-octabutoxy-naphthalocyanine

Incubation of B78H1 amelanotic melanoma cells with a potential photothermal sensitizer, namely, liposome-incorporated Ni(II)-octabutoxy-naphthalocyanine (NiNc), induces an appreciable cellular accumulation of the naphthalocyanine, which is dependent on both the NiNc concentration and the incubation time. No detectable decrease in cell survival occurs upon red-light irradiation (corresponding to the longest-wavelength absorption bands of NiNc) in a continuous-wave (c.w.) regime of the naphthalocyanine-loaded cells. On the other hand, 850 nm irradiation with a Q-switched Ti:sapphire laser operating in a pulsed mode (30 ns pulses, 10 Hz, 200 mJ/pulse) induces an efficient cell death. Thus, ca. 98% decrease in cell survival is obtained upon 5 min irradiation of cells that have been incubated for 48 h with 5.1 μM NiNc. The efficiency of the photoprocess is strongly influenced by the NiNc cell incubation time prior to irradiation. Photothermal sensitization with NiNc appears to open new perspectives for therapeutic applications, as suggested by preliminary in vivo studies with C57/BL6 mice bearing a subcutaneously implanted amelanotic melanoma.

Irradiation of Amelanotic Melanoma Cells with 532 nm High Peak Power Pulsed Laser Radiation in the Presence of the Photothermal Sensitizer Cu(II)‐Hematoporphyrin: A New Approach to Cell Photoinactivation

Cu(II)-hematoporphyrin (CuHp) was efficiently accumulated by B78H1 amelanotic melanoma cells upon incubation with porphyrin concentrations up to 52 microM. When the cells incubated for 18 h with 13 microM CuHp were irradiated with 532 nm light from a Q-switched Nd: YAG laser operated in a pulsed mode (10 ns pulses, 10 Hz) a significant decrease in cell survival was observed. The cell photoinactivation was not the consequence of a photodynamic process, as CuHp gave no detectable triplet signal upon laser flash photolysis excitation and no decrease in cell survival was observed upon continuous wave irradiation. Thus, it is likely that CuHp sensitization takes place by photothermal pathways. The efficiency of the photoprocess was modulated by different parameters; thus, while varying the amount of added CuHp in the 3.25-26 microM range had little effect, pulse energies larger than 50 mJ and irradiation times of at least 120 s were necessary to induce a cell inactivation of about 50%. The porphyrin-cell incubation time prior to irradiation had a major influence on cell survival, suggesting that the nature of the CuHp microenvironment can control the efficiency of photothermal sensitization.

Novel approaches towards a detailed control of the mechanism and efficiency of photosensitized processes in vivo

The photoexcitation of an endogenous or exogenous biological chromophore can result in the re-emission of light as fluorescence or phosphorescence; this may be used for photodiagnostic applications or in the conversion of at least part of the absorbed radiation into thermal or chemical energy. The last two processes generate photothermal and photochemical sensitization respectively leading to the irreversible damage of cells and tissues; hence they can be used for phototherapeutic purposes. The efficacy and scope of photodiagnostic and phototherapeutic techniques are improving as we increase our knowledge about the influence of biological microenvironments on the mechanisms of photoprocesses and as new approaches are developed for controlling the biodistribution of photosensitizing agents in vivo and the depth/diffusion of incident light into tissues. In particular, even the localized and sublethal damage of cells can often be modulated to generate intracellular signalling in order to either induce a programmed cell death (apoptosis) or an acceleration of cell metabolism (photostimulation).

Liquid-crystal phase transitions of thin layers: A photothermal analysis

A numerical analysis of the photothermal probe-beam signal generated at first- and second-order phase transitions in 4-n-octyl-4'-cyanobiphenyl (8CB) is proposed. A criterion for photothermal signal sensitivity in detection of phase transitions is given. The influences of probe-beam transverse offset and modulation frequency, as well as thermal parameters of the probed medium, on this sensitivity are investigated experimentally and theoretically. It is shown that the photothermal signal may be insensitive to the phase transitions for certain values of the modulation frequency and the probe-beam transverse offset, while a maximum of sensitivity is obtained for a range of values of these parameters. It is also shown that this sensitivity is improved if we use a probed medium with an effusivity smaller than the sample effusivity. A comparison of some of the results of the theory with experimental results is given.

Photothermal sensitizers: Possible use in tumor therapy

Photothermal damage of tissues or endotissular compartments may be induced by pulsed irradiation of either endogenous chromophores ( e.g. hemoglobin, melanin) or externally added dyes; the latter should have short triplet lifetimes and mainly decay from electronically excited states by non-radiative pathways. Potential photothermal sensitizers are some metallo derivatives of porphyrins and porphyrinoid compounds, azo dyes and triphenylmethane derivatives. These dyes have the additional property of significant absorbance at wavelengths longer than 600 nm, which can penetrate deep into biological tissues. Spatial confinement of the photothermal process depends on the absorption coefficient of the photoexcited chromophore and its thermal relaxation time. Present evidence indicates that the selective photothermal damage of macromolecules or subcellular organelles requires pulsed excitation at picosecond or nanosecond regimes, while microsecond or millisecond domains are effective in the case of cells or similar structures. The possible use of photothermal sensitization in the treatment of tumors is briefly discussed.

Response of Wheat Genotypes to Temperature and Photoperiod in Natural Conditions

Floral initiation in wheat (Triticum aestivum L.) depends on complex interactions between temperature and photoperiod. The aim of this study was to analyze genetic variation in the response to combined variations of changing and often suboptimal photoperiods and temperatures as they occur in natural environments. Twelve genotypes were analyzed in the field, using vernalized and nonvernalized seeds, for times of floral initiation, anthesis, and beginning of stem elongation. Climate was varied by changing sowing date, year, and site. This resulted in large variations in the date of achievement of all stages. However, these variations could be expressed by a unique curve for each genotype when dates were characterized by the combination of the thermal time from seedling emergence (K) and of the daylength (P) on the date considered. The curve was specific to a stage and to a genotype. The curves obtained for the different genotypes were variants of the same general curve, which allowed definition and quantitative assessment of three characteristics for describing the developmental response of a genotype to climate: vernalization requirements, photothermal sensitivity, and intrinsic earliness. These three components, which are confounded in the common notion of earliness, showed large variations among genotypes, especially at the lemma stage. They were largely independent. Our results also show that, compared to differences in the sensitivity to photoperiod and temperature, differences in vernalization requirements are of secondary importance in choosing a genotype in temperate areas, even for a very late spring sowing.