Light-activated, photosensitizer-based therapies have been established as safe modalities of tumour ablation for numerous cancer indications. Two main approaches are available: photodynamic therapy, which results in localized chemical damage in the target lesions, and photothermal therapy, which results in localized thermal damage. Whereas the administration of photosensitizers is a key component of photodynamic therapy, exogenous photothermal contrast agents are not required for photothermal therapy but can enhance the efficiency and efficacy of treatment. Over the past decades, great strides have been made in the development of phototherapeutic drugs and devices as cancer treatments, but key challenges have restricted their widespread clinical use outside of certain dermatological indications. Improvements in the tumour specificity of photosensitizers, achieved through targeting or localized activation, could provide better outcomes with fewer adverse effects, as could combinations with chemotherapies or immunotherapies. In this Review, we provide an overview of the current clinical progress of phototherapies for cancer and discuss the emerging preclinical bioengineering approaches that have the potential to overcome challenges in this area and thus improve the efficiency and utility of such treatments.

Clinical development and potential of photothermal and photodynamic therapies for cancer

Nonlinear Optical Crystals: A Complete Survey

Photochemistry at adsorbate/metal interfaces

Standards which eliminate ambiguity in reporting nonlinear phenomena, especially in the increasingly complex realm of biaxial crystals, are proposed. In order to restore uniformity to the designation of crystallographic axes and crystal tensor properties, adoption of IEEE/ANSI Std. 176, with a small but much needed modification for crystal class mm2, is recommended. For the reporting of nonlinear interaction characteristics, other frames are proposed which result in simpler rules than heretofore given for categorizing phase-matching loci, and for characterizing eigenmode polarizations, double refraction, effective nonlinear coupling, and first- and second-order acceptance bandwidths (angular, spectral, thermal) along these loci. Similarities as well as differences between biaxial and uniaxial crystals are emphasized. >

Simplified characterization of uniaxial and biaxial nonlinear optical crystals: a plea for standardization of nomenclature and conventions

Laser-induced gas-surface interactions

A refractive laser surgery process is disclosed for using compact, low-cost ophthalmic laser systems which have computer-controlled scanning with a non-contact delivery device for both photo-ablation and photo-coagulation in corneal reshaping. The basic laser systems may include flash-lamp and diode pumped UV solid state lasers (193-215 nm), compact excimer laser (193 nm), free-running Er:glass (1.54 microns), Ho:YAG (2.1 microns), Q-switched Er:YAG (2.94 microns), and tunable IR lasers, (750-1100) nm and (2.5-3.2) microns. The advantages of the non-contact, scanning device used in the process over other prior art lasers include being safer, reduced cost, more compact and more precise and with greater flexibility. The theory of beam overlap and of ablation rate and coagulation patterns is also disclosed for system parameters. Lasers are selected with energy of (0.01-10) mJ, repetition rate of (1-10,000), pulse duration of 0.01 nanoseconds to a few hundreds of microseconds, and with spot size of (0.05-2) mm for use with refractive laser surgery.

Ophthalmic surgery method using non-contact scanning laser

We present a novel pulsed-train near-IR diode laser system with real-time temperature monitoring of the laser-heated cancer cell mixed in gold nanorod solution. Near-IR diode laser at 808nm matching the gold nanorod absorption peak (with an aspect ratio about 4.0) was used in this study. Both surface and volume temperatures were measured and kept above 43°C, the temperature for cancer cells destruction. The irradiation time needed in our pulsed-train system with higher laser fluence for killing the cancel cells is about 1-3 minutes, much shorter than conventional methods (5-10 minutes). Cell viabilities in gold nanorod mixed and controlled solutions are studied by green fluorescence.

https://downloads.hindawi.com/journals/jnm/2012/861385.pdf

In vitro photothermal destruction of cancer cells using gold nanorods and pulsed-train near-infrared laser

A study is made of photoablation of the porcine cornea and synthetic collagen with 213-nm radiation generated by the fifth harmonic from a Q-switched Nd:YAG laser. The new nonlinear crystals, beta barium borate (BBO), with specific angle cutting were used to optimize the fifth-harmonic generation (213 nm). For comparison purposes, the above materials were also ablated by 266-nm (fourth-harmonic) laser radiation. Light and electron microscopy demonstrated that the damage zones created by 213- and 266-nm radiation are >

Ablation of the cornea and synthetic polymers using a UV (213 nm) solid-state laser

Surface temperatures generated by gaussian, rectangular, and triangular laser pulses are determined by solving a heat diffusion equation. The dependence of the temperature on the pulse shape and, in turn, the dependence of the thermal diffusivity and absorptance on the temperature are investigated. The lifetime of an adspecies on a laser‐heated solid (e.g., Cs on W) is estimated in terms of the temperature, the desorption energy, and the coverage. The mechanism of laser‐generated electron emission from the adspecies is analyzed by means of the Richardson equation. A condition for generating an intense electron beam is that the laser pulse duration and the rise time of the temperature must be less than the lifetime of the adspecies.

https://apps.dtic.mil/sti/pdfs/ADA114282.pdf

Laser-Generated Electron Emission from Surfaces: Effect of the Pulse Shape on Temperature and Transient Phenomena.

Objective 
Analysis of the crosslink time, depth and efficacy profiles of UV-light-activated corneal collagen crosslinking (CXL).


Methods 
A modeling system described by a coupled dynamic equations are numerically solved and analytic formulas are derived for the crosslinking time (T*) and crosslinking depth (z*). The z-dependence of the CXL efficacy is numerically produced to show the factors characterizing the profiles.


Results 
Optimal crosslink depth (z*) and maximal CXL efficacy (Ceff) have opposite trend with respective to the UV light intensity and RF concentration, where z* is a decreasing function of the riboflavin concentration (C0). In comparison, Ceff is an increasing function of C0 and the UV exposure time (for a fixed UV dose), but it is a decreasing function of the UV light intensity. CXL efficacy is a nonlinear increasing function of [C0/I0]-0.5 and more accurate than that of the linear theory of Bunsen Roscoe law. Depending on the UV exposure time and depth, the optimal intensity ranges from 3 to 30 mW/cm2 for maximal CXL efficacy. For steady state (with long exposure time), low intensity always achieves high efficacy than that of high intensity, when same dose is applied on the cornea.


Conclusions 
The crosslinking depth (z*) and the crosslinking time (T*) have nonlinear dependence on the UV light dose and the efficacy of corneal collagen crosslinking should be characterized by both z* and the efficacy profiles. A nonlinear scaling law is needed for more accurate protocol.

/pdf/modeling-the-efficacy-profiles-of-uv-light-activated-corneal-j5funv9t67.pdf

Jui-Teng Lin

Papers

Ophthalmic surgery method using non-contact scanning laser

In vitro photothermal destruction of cancer cells using gold nanorods and pulsed-train near-infrared laser

Ablation of the cornea and synthetic polymers using a UV (213 nm) solid-state laser

Laser-Generated Electron Emission from Surfaces: Effect of the Pulse Shape on Temperature and Transient Phenomena.

Modeling the efficacy profiles of UV-light activated corneal collagen crosslinking.