Iodinated cyanine dye-based nanosystem for synergistic phototherapy and hypoxia-activated bioreductive therapy

Abstract

Photodynamic therapy (PDT) has been applied in cancer treatment by utilizing reactive oxygen species (ROS) to kill cancer cells. However, the effectiveness of PDT is greatly reduced due to local hypoxia. Hypoxic activated chemotherapy combined with PDT is expected to be a novel strategy to enhance anti-cancer therapy. Herein, a novel liposome (LCT) incorporated with photosensitizer (PS) and bioreductive prodrugs was developed for PDT-activated chemotherapy. In the design, CyI, an iodinated cyanine dye, which could simultaneously generate enhanced ROS and heat than other commonly used cyanine dyes, was loaded into the lipid bilayer; while tirapazamine (TPZ), a hypoxia-activated prodrug was encapsulated in the hydrophilic nucleus. Upon appropriate near-infrared (NIR) irradiation, CyI could simultaneously produce ROS and heat for synergistic PDT and photothermal therapy (PTT), as well as provide fluorescence signals for precise real-time imaging. Meanwhile, the continuous consumption of oxygen would result in a hypoxia microenvironment, further activating TPZ free radicals for chemotherapy, which could induce DNA double-strand breakage and chromosome aberration. Moreover, the prepared LCT could stimulate acute immune response through PDT activation, leading to synergistic PDT/PTT/chemo/immunotherapy to kill cancer cells and reduce tumor metastasis. Both in vitro and in vivo results demonstrated improved anticancer efficacy of LCT compared with traditional PDT or chemotherapy. It is expected that these iodinated cyanine dyes-based liposomes will provide a powerful and versatile theranostic strategy for tumor target phototherapy and PDT-induced chemotherapy.

Ligand-regulated three-photon AIE properties of manganese(ii) complexes for photodynamic therapy

“…This is due to the heavy atom effect of the halogen atoms, which decreases the 1 O 2 yield of the substance after the introduction of the halogen atoms. 22,23 Therefore, the heavy atom effect connects the three-photon cross-section and the 1 O 2 yield of the substance, resulting in an inverse relationship between the two. Compared with the 1 O 2 yields of other noble metals as photodynamic materials, the 1 O 2 yields of MD3 are higher (Table S7 †).…”

“…Our synthesized halogenated carbazole-based manganese complex with AIE properties is expected to replace precious metal materials (such as Ir, Pt, and Ru) as a new and inexpensive photosensitizer. [15][16][17] The carbazolyl trispyridyl ligand is an N^N^N^type tridentate ligand and can chelate with manganese ions in an almost planar coordination geometry to form stable complexes, which are beneficial for the three-photon activity. MD1-MD3 all exhibit three-photon AIE properties.…”

An Activity‐Based Photosensitizer to Reverse Hypoxia and Oxidative Resistance for Tumor Photodynamic Eradication

“…[ 1 ] PDT takes advantage of the local reactive oxygen species (ROS) engendered by the systemic administration of photosensitizers (PS) through laser irradiation in the focused area. [ 2 ] The oxidative lesions trigger cell apoptosis, seal blood vessels, and eventually eliminate the nidus. [ 3 ] However, during the accelerated growth of tumors, O 2 consumption exceeds O 2 supply, and the hypoxia tumor microenvironment (TME) can develop gradually with increasing distance from the tumor‐associated vasculature.…”

Recent Development of Photoresponsive Liposomes Based on Organic Photosensitizers, Au Nanoparticles, and Azobenzene Derivatives for Nanomedicine

“…For example, adding organic photosensitizers to vehicles can increase the local temperature by their photothermal effect, improve blood flow and oxygenation within the tumor, and induce tumor ablation by combining photodynamic therapy and chemotherapy. 13,14 This is a well-established strategy for photoresponsive liposomes in nanomedicine applications. Introducing azobenzene derivatives into liposomal bilayers can achieve isomeric conversion upon light exposure and drive structural changes in phospholipid molecules, resulting in rapid release of encapsulated material 15 (Figure 1).…”

“…The former is classified as the photothermal effect, while the latter is the photoisomerization effect (in a fraction of liposomes prepared from thermosensitive lipids, light is still the initial condition that triggers a series of dynamic reactions for which they were classified as photoresponsive liposomes). For example, adding organic photosensitizers to vehicles can increase the local temperature by their photothermal effect, improve blood flow and oxygenation within the tumor, and induce tumor ablation by combining photodynamic therapy and chemotherapy. , This is a well-established strategy for photoresponsive liposomes in nanomedicine applications. Introducing azobenzene derivatives into liposomal bilayers can achieve isomeric conversion upon light exposure and drive structural changes in phospholipid molecules, resulting in rapid release of encapsulated material (Figure ).…”