Optimizing Irradiation Geometry in LED-Based Photoacoustic Imaging with 3D Printed Flexible and Modular Light Delivery System.

Photoacoustic (PA) imaging-a technique combining the ability of optical imaging to probe functional properties of the tissue and deep structural imaging ability of ultrasound-has gained significant popularity in the past two decades for its utility in several biomedical applications. More recently, light-emitting diodes (LED) are being explored as an alternative to bulky and expensive laser systems used in PA imaging for their portability and low-cost. Due to the large beam divergence of LEDs compared to traditional laser beams, it is imperative to quantify the angular dependence of LED-based illumination and optimize its performance for imaging superficial or deep-seated lesions. A custom-built modular 3-D printed hinge system and tissue-mimicking phantoms with various absorption and scattering properties were used in this study to quantify the angular dependence of LED-based illumination. We also experimentally calculated the source divergence of the pulsed-LED arrays to be 58° ± 8°. Our results from point sources (pencil lead phantom) in non-scattering medium obey the cotangential relationship between the angle of irradiation and maximum PA intensity obtained at various imaging depths, as expected. Strong dependence on the angle of illumination at superficial depths (-5°/mm at 10 mm) was observed that becomes weaker at intermediate depths (-2.5°/mm at 20 mm) and negligible at deeper locations (-1.1°/mm at 30 mm). The results from the tissue-mimicking phantom in scattering media indicate that angles between 30-75° could be used for imaging lesions at various depths (12 mm-28 mm) where lower LED illumination angles (closer to being parallel to the imaging plane) are preferable for deep tissue imaging and superficial lesion imaging is possible with higher LED illumination angles (closer to being perpendicular to the imaging plane). Our results can serve as a priori knowledge for the future LED-based PA system designs employed for both preclinical and clinical applications.

Near Infrared Photoimmunotherapy with Combined Exposure of External and Interstitial Light Sources.

Near infrared photoimmunotherapy (NIR-PIT) is a new target-cell-specific cancer treatment that induces highly selective necrotic/immunogenic cell death after systemic administration of a photoabsorber antibody conjugate and subsequent NIR light exposure. However, the depth of NIR light penetration in tissue (approximately 2 cm) with external light sources limits the therapeutic effects of NIR-PIT. Interstitial light exposure using cylindrical diffusing optical fibers can overcome this limitation. The purpose in this study was to compare three NIR light delivery methods for treating tumors with NIR-PIT using a NIR laser system at an identical light energy; external exposure alone, interstitial exposure alone, and the combination. Panitumumab conjugated with the photoabsorber IRDye-700DX (pan-IR700) was intravenously administered to mice with A431-luc xenografts which are epithelial growth factor receptor (EGFR) positive. One and 2 days later, NIR light was administered to the tumors using one of three methods. Interstitial exposure alone and in combination with external sources showed the greatest decrease in bioluminescence signal intensity. Additionally, the combination of external and interstitial NIR light exposure showed significantly greater tumor size reduction and prolonged survival after NIR-PIT compared to external exposure alone. This result suggested that the combination of external and interstitial NIR light exposure was more effective than externally applied light alone. Although external exposure is the least invasive means of delivering light, the combination of external and interstitial exposures produces superior therapeutic efficacy in tumors greater than 2 cm in depth from the tissue surface.

Light dose versus rate of delivery: implications for macroalgal productivity.

The role of how light is delivered over time is an area of macroalgal photosynthesis that has been overlooked but may play a significant role in controlling rates of productivity and the structure and persistence of communities. Here we present data that quantify the relative influence of total quantum dose and delivery rate on the photosynthetic productivity of five ecologically important Phaeophyceae species from southern New Zealand. Results suggested that greater net oxygen production occurs when light is delivered at a lower photon flux density (PFD) over a longer period compared to a greater PFD over a shorter period, given the same total dose. This was due to greater efficiency (α) at a lower PFD which, for some species, meant a compensatory effect can occur. This resulted in equal or greater productivity even when the total quantum dose of the lower PFD was significantly reduced. It was also shown that light limitation at Huriawa Peninsula, where macroaglae were sourced, may be restricting the acclimation potential of species at greater depths, and that even at shallow depth periods of significant light limitation are likely to occur. This research is of particular interest as the variability of light delivery to coastal reef systems increases as a result of anthropogenic disturbances, and as the value of in situ community primary productivity estimates is recognised.

Emerging Targets in Photopharmacology.

The field of photopharmacology uses molecular photoswitches to establish control over the action of bioactive molecules. It aims to reduce systemic drug toxicity and the emergence of resistance, while achieving unprecedented precision in treatment. By using small molecules, photopharmacology provides a viable alternative to optogenetics. We present here a critical overview of the different pharmacological targets in various organs and a survey of organ systems in the human body that can be addressed in a non-invasive manner. We discuss the prospects for the selective delivery of light to these organs and the specific requirements for light-activatable drugs. We also aim to illustrate the druggability of medicinal targets with recent findings and emphasize where conceptually new approaches have to be explored to provide photopharmacology with future opportunities to bring "smart" molecular design ultimately to the realm of clinical use.

Optical Microneedle-Lens Array for Selective Photothermolysis.

Photothermolysis is the process that converts radiation energy into thermal energy, which results in the destruction of surrounding tissues or cells through thermal diffusion. Laser therapy that is based on photothermolysis has been a widely used treatment for various skin diseases such as skin cancers and port-wine stains. It offers several benefits such as non-invasiveness and selective treatment. However, the use of light, e.g., laser, for safe and effective photothermolysis becomes challenging due to the limited penetration of light into skin tissue as well as the presence of melanin, which absorbs this light. To solve the current issues, we propose an optical microneedle-lens array (OMLA) coated with gold in this work to directly deliver light to targeted skin layers without being absorbed by surrounding tissues as well as melanin, which results in the improvement of the efficiency of photothermal therapy. We developed a novel fabrication method, frame-guided micromolding, to prepare the OMLA by assembling two negative molds with simultaneous alignment. In addition, evaluations of the optical and heat transfer characteristics of the OMLA were performed. We expect our developed OMLA to play a crucial role in realizing more effective laser therapy by allowing the precise delivery of photons to the target area.

Efficacy of interstitial photodynamic therapy using talaporfin sodium and a semiconductor laser for a mouse allograft glioma model.

To investigate the therapeutic potential of photodynamic therapy (PDT) for malignant gliomas arising in unresectable sites, we investigated the effect of tumor tissue damage by interstitial PDT (i-PDT) using talaporfin sodium (TPS) in a mouse glioma model in which C6 glioma cells were implanted subcutaneously. A kinetic study of TPS demonstrated that a dose of 10 mg/kg and 90 min after administration was appropriate dose and timing for i-PDT. Performing i-PDT using a small-diameter plastic optical fiber demonstrated that an irradiation energy density of 100 J/cm2 or higher was required to achieve therapeutic effects over the entire tumor tissue. The tissue damage induced apoptosis in the area close to the light source, whereas vascular effects, such as fibrin thrombus formation occurred in the area slightly distant from the light source. Furthermore, when irradiating at the same energy density, irradiation at a lower power density for a longer period of time was more effective than irradiation at a higher power density for a shorter time. When performing i-PDT, it is important to consider the rate of delivery of the irradiation light into the tumor tissue and to set irradiation conditions that achieve an optimal balance between cytotoxic and vascular effects.

The efficacy of LED microneedle patch on hair growth in mice.

Light penetration depth in the scalp is a key limitation of low-level light therapy for the treatment of androgenetic alopecia (AGA). A novel light emitting diode (LED) microneedle patch was designed to achieve greater efficacy by enhancing the percutaneous light delivery. The study aimed to investigate the efficacy and safety of this device on hair growth in mice. Thirty-five male C57BL/6 mice which their dorsal skin was split into upper and lower parts to receive either LED irradiation alone or LED irradiation with a microneedle patch. Red (629 nm), green (513 nm), and blue light (465 nm) at an energy dose of 0.2 J/cm2 were applied once daily for 28 days. Outcomes were evaluated weekly using digital photographs. Histopathological findings were assessed using a 6 mm punch biopsy. A significant increase in hair growth was observed in the green light, moderate in the red light, and the lowest in the blue light group. The addition of the microneedle patch to LED irradiation enhanced greater and faster anagen entry in all the groups. Histopathology showed an apparent increase in the number of hair follicles, collagen bundles in the dermis, angiogenesis, and mononuclear cell infiltration after treatment with the green-light LED microneedle patches. No serious adverse effects were observed during the experiment. Our study provides evidence that the newly developed green-light LED microneedle patch caused the optimal telogen-to-anagen transition and could lead to new approaches for AGA. Microneedle stimulation may aid percutaneous light delivery to the target hair follicle stem cells.

Emerging optogenetics technologies in biomedical applications.

Optogenetics is a cutting-edge technology that merges light control and genetics to achieve targeted control of tissue cells. Compared to traditional methods, optogenetics offers several advantages in terms of time and space precision, accuracy, and reduced damage to the research object. Currently, optogenetics is primarily used in pathway research, drug screening, gene expression regulation, and the stimulation of molecule release to treat various diseases. The selection of light-sensitive proteins is the most crucial aspect of optogenetic technology; structural changes occur or downstream channels are activated to achieve signal transmission or factor release, allowing efficient and controllable disease treatment. In this review, we examine the extensive research conducted in the field of biomedicine concerning optogenetics, including the selection of light-sensitive proteins, the study of carriers and delivery devices, and the application of disease treatment. Additionally, we offer critical insights and future implications of optogenetics in the realm of clinical medicine.

Non-Invasive Treatment of Early Diabetic Macular Edema by Multiwavelength Photobiomodulation with the Valeda Light Delivery System.

Purpose: Diabetes is associated with ocular complications including diabetic macular edema (DME). Current therapies are invasive and include repeated intravitreal injections and laser therapy. Photobiomodulation (PBM) is a treatment (Tx) that utilizes selected wavelengths of light to induce cellular benefits including reduction of inflammation and edema. This single-center, open-label, post-hoc analysis explored the utility of multiwavelength PBM in subjects with DME. Methods: Analysis included review of data from patients undergoing standard clinical care with an approved and marketed PBM medical device, the Valeda® Light Delivery System. Subjects with early-stage DME with good vision (Best-corrected visual acuity (BCVA) > 20/25, logMAR > 0.1) were evaluated in clinic and treated with one series of multiwavelength PBM (Tx delivered 3x/week over 3-4 weeks; total of 9 Tx sessions). Clinical, anatomical, and safety parameters were assessed in addition to subjective quality of life. Results: A total of 30 eyes (19 subjects) were analyzed. Subjects were predominately male (68.4%) with a mean age of 56 ± 14 years. Reductions in central retinal thickness (CRT), resolution of intraretinal fluid (IRF) and improvement in diabetic retinopathy severity scale scores were observed following PBM treatment in select patients. Baseline BCVA remained stable over the follow-up observation period of 3 months post-PBM. Approximately 64% of patients reported subjective improvements in their ocular condition and decreased influence in everyday life. Detailed OCT evaluations confirmed no safety issues related to phototoxicity up to 16 months. Conclusion: Early-stage DME subjects treated with Valeda multiwavelength PBM showed improvements in clinical and anatomical parameters. The Valeda multiwavelength PBM approach demonstrates a favorable safety profile with no signs of phototoxicity following an independent OCT review. PBM therapy may offer an alternative, non-invasive treatment strategy with a unique mechanism and modality for patients with early-stage DME.

Recent advances in cellular optogenetics for photomedicine.

Since the successful introduction of exogenous photosensitive proteins, channelrhodopsin, to neurons, optogenetics has enabled substantial understanding of profound brain function by selectively manipulating neural circuits. In an optogenetic system, optical stimulation can be precisely delivered to brain tissue to achieve regulation of cellular electrical activity with unprecedented spatio-temporal resolution in living organisms. In recent years, the development of various optical actuators and novel light-delivery techniques has greatly expanded the scope of optogenetics, enabling the control of other signal pathways in non-neuronal cells for different biomedical applications, such as phototherapy and immunotherapy. This review focuses on the recent advances in optogenetic regulation of cellular activities for photomedicine. We discuss emerging optogenetic tools and light-delivery platforms, along with a survey of optogenetic execution in mammalian and microbial cells.

Materials and device design for advanced phototherapy systems.

Phototherapy has recently emerged as a promising solution for cancer treatment due to its multifunctionality and minimal invasiveness. Notwithstanding the limited penetration depth of light through skin, the ability of photopharmaceutical device systems to deliver light to desired lesions is important. The device system deploys advanced biocompatible materials and fabrication technologies for electronics, and eventually enables more efficient phototherapy. In this review, we focus on diverse optical electronics to illuminate the lesion site with light. Then, moving on to the phototherapy, we highlight photo-thermal therapy with light absorbing materials, photo-activated chemotherapy with light sensitive materials, and photo-dynamic therapy using photosensitizers. Furthermore, we introduce a drug delivery system that can deliver these photopharmaceutical agents spatiotemporally to the tumor site. To this end, we provide a general overview of materials and devices for phototherapy and discuss critical issues and pending limitations of such phototherapy.

Steering light in fiber-optic medical devices: a patent review.

INTRODUCTION: Steering light is relevant to many medical applications that require tissue illumination, sensing, or modification. To control the propagation direction of light beams, a great variety of innovative fiber-optic medical devices have been designed. AREAS COVERED: This review provides a comprehensive overview of the patent literature on light beam control in fiber-optic medical devices. The Web of Science Derwent Innovation Index database was scanned, and 81 patents on fiber-optic devices published in the last 20 years (2001-2021) were retrieved and categorized based on the working principle to steer light (refraction/reflection, scattering, diffraction) and the design strategy that was employed (within fiber, at fiber end, outside fiber). EXPERT OPINION: Patents describing medical devices were found for all categories, except for generating diffraction at the fiber end surface. The insight in the different designs reveals that there are still several opportunities to design innovative devices that can collect light at an angle off-axis, reduce the angular distribution of light, or split light into multiple beams.

Inside-the-body light delivery system using endovascular therapy-based light illumination technology.

BACKGROUND: Light-based therapies are promising for treating diseases including cancer, hereditary conditions, and protein-related disorders. However, systems, methods, and devices that deliver light deep inside the body are limited. This study aimed to develop an endovascular therapy-based light illumination technology (ET-BLIT), capable of providing deep light irradiation within the body. METHODS: The ET-BLIT system consists of a catheter with a single lumen as a guidewire and diffuser, with a transparent section at the distal end for thermocouple head attachment. The optical light diffuser alters the emission direction laterally, according to the optical fibre's nose-shape angle. If necessary, after delivering the catheter to the target position in the vessel, the diffuser is inserted into the catheter and placed in the transparent section in the direction of the target lesion. FINDINGS: ET-BLIT was tested in an animal model. The 690-nm near-infrared (NIR) light penetrated the walls of blood vessels to reach the liver and kidneys without causing temperature increase, vessel damage, or blood component alterations. NIR light transmittance from the diffuser to the detector within the organ or vessel was approximately 30% and 65% for the renal and hepatic arteries, respectively. INTERPRETATION: ET-BLIT can be potentially used in clinical photo-based medicine, as a far-out technology. ET-BLIT uses a familiar method that can access the whole body, as the basic procedure is comparable to that of endovascular therapy in terms of sequence and technique. Therefore, the use of the ET-BLIT system is promising for many light-based therapies that are currently in the research phase. FUNDING: Supported by Programme for Developing Next-generation Researchers (Japan Science and Technology Agency); JSPS KAKENHI (18K15923, 21K07217); JST-CREST (JPMJCR19H2); JST-FOREST-Souhatsu (JPMJFR2017); The Uehara Memorial Foundation; Yasuda Memorial Medical Foundation; Mochida Memorial Foundation for Medical and Pharmaceutical Research; Takeda Science Foundation; The Japan Health Foundation; Takahashi Industrial and Economic Research Foundation; AICHI Health Promotion Foundation; and Princess Takamatsu Cancer Research Fund.

Enhancing CO2 photo-biochemical conversion in a newly-designed attached photobioreactor characterized by stacked horizontal planar waveguide modules.

Aiming at alleviating the adverse effects on attached microalgae biofilm growth caused by heterogeneous spatial light distributions within the attached cultivation photobioreactors (PBRs), an innovative PBR integrated with stacked horizontal planar waveguide modules (SHPW-PBR) was proposed in this work. Different from the conventional PBR, the emergent light from the external LED light bars were guided and evenly redistributed within the SHPW-PBR by the planar waveguides and hence provided light energy for microalgae cells photoautotrophic growth. In comparison with the control PBR, the average light intensity illuminating the attached Chlorella vulgaris biofilm in the SHPW-PBR was elevated by 204.11% and contributed to a 145.20% improvement on areal C. vulgaris biofilm production. Thereafter, responses of attached C. vulgaris biofilm growth in the SHPW-PBR to various light intensities were evaluated and the maximum areal C. vulgaris biofilm density reached 90.43 g m-2 under the light intensity of 136 µmol m-2 s-1 after 9 days cultivation. Furthermore, the SHPW-PBR can be easily scaled-up by increasing the quantity of the stacked planar waveguide modules and thus shows great potential in biofilm-based biomass production.

Light delivery device modelling for homogenous irradiation distribution in photodynamic therapy of non-spherical hollow organs.

SIGNIFICANCE: Photodynamic therapy (PDT) is a useful treatment for select cancers. Homogeneous illumination is a key factor in the successful application of PDT treatment of tumours in hollow organs. Over illumination may damage normal tissue while under illumination may not ablate the target. BACKGROUND: There have been many approaches to provide homogeneous irradiation for PDT treatment of hollow organs, including light-scattering medium and isotropic emitter to diffuse light, a balloon filled with solution to expand the organ wall, and shaped fibres. In most studies, the organ is assumed to be spherical. However, many hollow organs treated by PDT are non-spherical, and the uniformity of azimuthal irradiation remains an unsolved problem for cylindrical light sources. OBJECTIVE: Find a design principle for homogeneous irradiation in a non-spherical cavity for PDT treatment. METHOD: A PDT light delivery device is modeled by a series of sub light sources placed along the longitudinal axis of an ellipsoid. In order to achieve a homogeneous azimuthal irradiation distribution on the elliptical arc, a cost function is solved by adding modulation coefficient to the emission profile. The coefficient of variation of uniformity (Ucov) describes the statistical dispersion of the variation in irradiation over the ellipsoid to the average value. Ucov is used to evaluate the homogeneity of the azimuthal irradiation distribution. RESULT: By minimizing the cost function, we found that the truncated Gaussian function can be chosen as the emission profile to generate homogeneous irradiation profile within an ellipsoid cavity model. The emission profile can be tailored to generate Ucov of 96.7 %. Further discussion shows that the light distribution could be generated practically by a side-emitting optical fibre, a LED array, or moving an isotropic emitter successively. The impact of emission angle of light sub-source is analysed and the irradiation profile from discrete longitudinal emissions is calculated. CONCLUSION: Theory analysis and simulation indicate that a cylindrical emitter with a non-uniform longitudinal emission profile (truncated Gaussian functions) results in an approximate homogeneous irradiance profile within an ellipsoidal cavity.

Optimized light delivery probe using ball lenses for co-registered photoacoustic and ultrasound endo-cavity subsurface imaging.

An optimized hand-held photoacoustic and ultrasound probe suitable for endo-cavity tumor subsurface imaging was designed and evaluated. Compared to previous designs, the prototype probe, consisting of four 1 mm multi-mode optical fibers attached with 1.5 mm diameter ball-shaped fiber tips sandwiched between a transvaginal ultrasound transducer and a custom-made sheath, demonstrated a higher light output and better beam homogeneity on tissue subsurface. The output power and fluence profile were simulated for different design parameters. A camera recorded fluence profiles through calibrated intralipid solution at various imaging depths. The light delivery efficiency was experimentally compared with and without the ball lenses, based on ex-vivo imaging of human colorectal cancer and in-vivo imaging of a palmar vein proximal to the human wrist. The simulations and experiments demonstrated that ball-shaped fiber tip design can achieve homogeneous fluence distribution on tissue subsurface with acceptable light output efficiency, suggesting its clinical potential for in-vivo endo-cavity imaging.

Principles of Optogenetic Methods and Their Application to Cardiac Experimental Systems.

Optogenetic techniques permit studies of excitable tissue through genetically expressed light-gated microbial channels or pumps permitting transmembrane ion movement. Light activation of these proteins modulates cellular excitability with millisecond precision. This review summarizes optogenetic approaches, using examples from neurobiological applications, and then explores their application in cardiac electrophysiology. We review the available opsins, including depolarizing and hyperpolarizing variants, as well as modulators of G-protein coupled intracellular signaling. We discuss the biophysical properties that determine the ability of microbial opsins to evoke reliable, precise stimulation or silencing of electrophysiological activity. We also review spectrally shifted variants offering possibilities for enhanced depth of tissue penetration, combinatorial stimulation for targeting different cell subpopulations, or all-optical read-in and read-out studies. Expression of the chosen optogenetic tool in the cardiac cell of interest then requires, at the single-cell level, introduction of opsin-encoding genes by viral transduction, or coupling "spark cells" to primary cardiomyocytes or a stem-cell derived counterpart. At the system-level, this requires construction of transgenic mice expressing ChR2 in their cardiomyocytes, or in vivo injection (myocardial or systemic) of adenoviral expression systems. Light delivery, by laser or LED, with widespread or multipoint illumination, although relatively straightforward in vitro may be technically challenged by cardiac motion and light-scattering in biological tissue. Physiological read outs from cardiac optogenetic stimulation include single cell patch clamp recordings, multi-unit microarray recordings from cell monolayers or slices, and electrical recordings from isolated Langendorff perfused hearts. Optical readouts of specific cellular events, including ion transients, voltage changes or activity in biochemical signaling cascades, using small detecting molecules or genetically encoded sensors now offer powerful opportunities for all-optical control and monitoring of cellular activity. Use of optogenetics has expanded in cardiac physiology, mainly using optically controlled depolarizing ion channels to control heart rate and for optogenetic defibrillation. ChR2-expressing cardiomyocytes show normal baseline and active excitable membrane and Ca2+ signaling properties and are sensitive even to ~1 ms light pulses. They have been employed in studies of the intrinsic cardiac adrenergic system and of cardiac arrhythmic properties.

Multichannel optrodes for photonic stimulation.

An emerging method in the field of neural stimulation is the use of photons to activate neurons. The possible advantage of optical stimulation over electrical is attributable to its spatially selective activation of small neuron populations, which is promising in generating superior spatial resolution in neural interfaces. Two principal methods are explored for cochlear prostheses: direct stimulation of nerves with infrared light and optogenetics. This paper discusses basic requirements for developing a light delivery system (LDS) for the cochlea and provides examples for building such devices. The proposed device relies on small optical sources, which are assembled in an array to be inserted into the cochlea. The mechanical properties, the biocompatibility, and the efficacy of optrodes have been tested in animal models. The force required to insert optrodes into a model of the human scala tympani was comparable to insertion forces obtained for contemporary cochlear implant electrodes. Side-emitting diodes are powerful enough to evoke auditory responses in guinea pigs. Chronic implantation of the LDS did not elevate auditory brainstem responses over 26 weeks.

Design of optimal light delivery system for co-registered transvaginal ultrasound and photoacoustic imaging of ovarian tissue.

A hand-held transvaginal probe suitable for co-registered photoacoustic and ultrasound imaging of ovarian tissue was designed and evaluated. The imaging probe consists of an ultrasound transducer and four 1-mm-core multi-mode optical fibers both housed in a custom-made sheath. The probe was optimized for the highest light delivery output and best beam uniformity on tissue surface, by simulating the light fluence and power output for different design parameters. The laser fluence profiles were experimentally measured through chicken breast tissue and calibrated intralipid solution at various imaging depths. Polyethylene tubing filled with rat blood mimicking a blood vessel was successfully imaged up to ∼30 mm depth through porcine vaginal tissue at 750 nm. This imaging depth was achieved with a laser fluence on the tissue surface of 20 mJ/cm(2), which is below the maximum permissible exposure (MPE) of 25 mJ/cm(2) recommended by the American National Standards Institute (ANSI). Furthermore, the probe imaging capability was verified with ex vivo imaging of benign and malignant human ovaries. The co-registered images clearly showed different vasculature distributions on the surface of the benign cyst and the malignant ovary. These results suggest that our imaging system has the clinical potential for in vivo imaging and characterization of ovarian tissues.

Advance in photosensitizers and light delivery for photodynamic therapy.

The brief history of photodynamic therapy (PDT) research has been focused on photosensitizers (PSs) and light delivery was introduced recently. The appropriate PSs were developed from the first generation PS Photofrin (QLT) to the second (chlorins or bacteriochlorins derivatives) and third (conjugated PSs on carrier) generations PSs to overcome undesired disadvantages, and to increase selective tumor accumulation and excellent targeting. For the synthesis of new chlorin PSs chlorophyll a is isolated from natural plants or algae, and converted to methyl pheophorbide a (MPa) as an important starting material for further synthesis. MPa has various active functional groups easily modified for the preparation of different kinds of PSs, such as methyl pyropheophorbide a, purpurin-18, purpurinimide, and chlorin e6 derivatives. Combination therapy, such as chemotherapy and photothermal therapy with PDT, is shortly described here. Advanced light delivery system is shown to establish successful clinical applications of PDT. Phtodynamic efficiency of the PSs with light delivery was investigated in vitro and/or in vivo.