Two-Photon Photodynamic Therapy

Bhawalkar, Jayant D.; Kumar, N. Deepak; Zhao, Chanfeng; Prasad, Paras N.

doi:10.1089/clm.1997.15.201

Cited by 530 publications

(311 citation statements)

References 11 publications

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“…However healthy tissues 65 which contain the photosensitiser may be damaged if they lie in the beam path. An additional degree of spatial selectivity may be achieved by two-photon excited photodynamic therapy [10][11][12] due to the quadratic dependence of the absorption probability on the light intensity. This approach has great potential for the treatment of 70 conditions where precise differentiation between healthy and diseased tissue is necessary, such as during the treatment of wet age-related macular degeneration (wet AMD) where abnormal blood vessels are targeted in the retina.…”

Section: Introductionmentioning

confidence: 99%

Photophysical properties and intracellular imaging of water-soluble porphyrin dimers for two-photon excited photodynamic therapy

et al. 2009

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Section: Introductionmentioning

confidence: 99%

Photophysical properties and intracellular imaging of water-soluble porphyrin dimers for two-photon excited photodynamic therapy

et al. 2009

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“…Multiphoton excitation using infrared light as irradiation source has been proposed and explored. [5][6][7][8][9] The new design of versatile PDT photosensitizers we propose is schematically shown in Figure 1. PUNPs are first coated with a porous, thin layer of silica.…”

mentioning

confidence: 99%

“…Multiphoton excitation using infrared light as irradiation source has been proposed and explored. [5][6][7][8][9] Experiment to combine photon upconverting materials with well-established PDT drug was mentioned, albeit with very limited efficiency in generating singlet oxygen. [10] The new design of versatile PDT photosensitizers we propose is schematically shown in Figure 1.…”

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confidence: 99%

Versatile Photosensitizers for Photodynamic Therapy at Infrared Excitation

et al. 2007

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A new type of photosensitizers used in photodynamic therapy, which is based on photon upconverting nanoparticles, is reported. These photosensitizers are excitable with infrared irradiation, which has several times larger tissue penetration depth than the currently available ones. They are brought close to the target cancer cells through antigen-antibody interaction with good specificity and versatility. The design is also flexible in that various photosensitive molecules can be potentially adopted into the design. Results from in vitro experiments demonstrate their promise of becoming the next generation photodynamic therapy drugs.Photodynamic therapy (PDT) is gaining acceptance as a technique for cancer treatment in recent years. [1][2][3] PDT utilizes a photosensitizer, working as a light-sensitive drug, to treat the target tissue locally upon the irradiation of light with appropriate wavelengths. It is generally accepted that the mechanism of PDT is based on the interaction between the excited photosensitizer and surrounding molecules, generating reactive oxygen species (ROS), such as singlet oxygen. ROS can cause oxidative damage to biological substrates and ultimately cell death. One of the key components in effective and efficient PDT is the photosensitizers, also called PDT drugs. Features most desired for an ideal PDT drug include: 1) Be specific to the target tissue; 2) Have a high photochemical reactivity, i.e., can effectively produce ROS when exposed to appropriate irradiation; 3) Exhibit little toxicity in the dark; and 4) Can be excited at a wavelength in the region where tissue penetration of irradiation is at a maximum. Here we report the design of a type of versatile photosensitizers, which could potentially satisfy all the above requirements and become the next generation PDT drugs, based on photon upconverting nanoparticles (PUNPs).Photon upconverting materials convert lower-energy light to higher-energy light through excitation with multiple photons. They have been widely used for some time in such applications as display, bioassay, and bioimaging, to name a few. [4] In this application, we take advantage of the fact that such materials would adsorb infrared irradiation and emit visible light to further excite the photosensitizing molecules. The particles of nanometer size would also facilitate the delivery and excretion of the proposed photosensitizer as PDT drug.The optimal spectral window for biological tissue penetration of irradiation is around 800 nm to 1 μm. Yet, single photons with infrared wavelengths are usually energetically too low for singlet oxygen generation. Multiphoton excitation using infrared light as irradiation source has been proposed and explored. [5][6][7][8][9] The new design of versatile PDT photosensitizers we propose is schematically shown in Figure 1. PUNPs are first coated with a porous, thin layer of silica. During the coating process, photosensitizing molecules with high absorbance in the spectral window matching the emission of the PUNPs are doped, ...

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“…The molecule was shown to have a high two-photon absorption efficiency at 800 nm excitation (two-photon absorption coefficient β = 1.45 cm/GW) and to transfer its energy to a PS in solution leading to singlet oxygen generation by indirect activation in presence of molecular oxygen [102]. Four years later another group demonstrated that singlet oxygen was efficiently generated by excitation of 4-(diphenylaminostilbene)-substituted porphyrin-based PSs molecularly designed for enhanced two-photon absorption at 780 nm (within the "tissue window") using a 150 femtosecond pulsed laser [50].…”

Section: Two-photon Pdt (2p-pdt)mentioning

confidence: 99%

New Approaches to Photodynamic Therapy from Types I, II and III to Type IV Using One or More Photons

Scherer

Bisby²,

Botchway³

et al. 2017

ACAMC

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Photodynamic therapy (PDT) is an alternative cancer treatment to conventional surgery, radiotherapy and chemotherapy. It is based on activating a drug with light that triggers the generation of cytotoxic species that promote tumour cell killing. At present, PDT is mainly used in the treatment of wet age-related macular degeneration, for precancerous conditions of the skin (e.g. actinic keratosis) and in the palliative care of advanced cancers, for instance of the bladder or the oesophagus. Due to a lack of phase III clinical trials and limitations of light penetration to deeper lying tumours (in excess of 1 cm), PDT is still not used as a first line cancer treatment, which is surprising given the first clinical trials by Dougherty's group dating back to the 1970's. However research continues to demonstrate the potential benefits of PDT and the need to stimulate funding and uptake of clinical studies using next generation photosensitizers offering advanced targeted delivery, improved photodynamic dose combined with modern light delivery technologies. This review surveys the available PDT treatments and emerging novel developments in the field with a particular focus on two-photon techniques that are anticipated to improve the effectiveness of PDT in tissues at depth and on next generation drugs that work without the need of the presence of oxygen for photosensitization making them effective where hypoxia has taken hold.

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Two-Photon Photodynamic Therapy

Cited by 530 publications

References 11 publications

Photophysical properties and intracellular imaging of water-soluble porphyrin dimers for two-photon excited photodynamic therapy

Photophysical properties and intracellular imaging of water-soluble porphyrin dimers for two-photon excited photodynamic therapy

Versatile Photosensitizers for Photodynamic Therapy at Infrared Excitation

New Approaches to Photodynamic Therapy from Types I, II and III to Type IV Using One or More Photons

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