Versatile Photosensitizers for Photodynamic Therapy at Infrared Excitation

Abstract

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, ...

Morphologically controlled synthesis of colloidal upconversion nanophosphors and their shape-directed self-assembly

“…Monodisperse UCNPs with distinct shapes are model systems to advance the understanding of the shape-directed assembly/packing behaviors of nanocolloids, but also open new opportunities in fields such as bioimaging (18,19) and photodynamic therapy (20,49). Programming anisotropic NCs to assemble into desired two-and three-dimensional patterns enables the production of complex nanoscale architectures useful for applications such as solar cells (46) and plasmonic metamaterials (50).…”

“…These NCs often possess "peculiar" optical properties [e.g., quantum cutting (16) and photon upconversion (17)], allowing the management of photons that could benefit a variety of areas including biomedical imaging (18,19) and therapy (20), photovoltaics (16,21), solid state lighting (22), and display technologies (23). Colloidal upconversion nanophosphors (UCNPs) are capable of converting long-wavelength near-infrared excitation into short-wavelength visible emission through the long-lived, metastable excited states of the lanthanide dopants (24).…”

Multifunctional upconversion–nanoparticles–trismethylpyridylporphyrin–fullerene nanocomposite: a near-infrared light-triggered theranostic platform for imaging-guided photodynamic therapy

“…UCNP-based PDT nanocomposites are considered promising platforms for cancer therapy due to the non-invasive manner and deep tissue penetration of NIR light, which breaks the dilemma of using UV or visible lights as irradiation source. Since Zhang et al 32 first demonstrated the application of UCNP-based nanocomposite for PDT of bladder cancer cells, recent advances in the integration of UCNPs with PSs such as chlorin e6, Rose Bengal, and IR825 (an NIR-absorbing dye) for their PDT applications in vitro and in vivo have created many excitements. [33][34][35] However, the phototoxic effect of 1 O 2 on PDT is restricted because of a hypoxic condition in tumor tissue.…”

Chemical modification of temoporfin – a second generation photosensitizer activated using upconverting nanoparticles for singlet oxygen generation

“…The application of Ln 3+ -UCNPs as an energy source for exciting photosensitizers has been proposed. [8][9][10][11][12][13] The nanoconstructs, which were prepared using upconverting nanoparticles for the excitation of different photosensitizers, made use of the Er 3+ transitions, 2 H 11/2 , 4 S 3/2 -4 I 11/2 and 4 F 9/2 -4 I 11/2 . The transitions have one major disadvantage, the emission from these transitions does not overlap with the strongest absorption peak, the Soret band, of the photosensitizer presently used, which is at B400 nm.…”