pheophytin-a and Neoplasms

To investigate and compare the pharmacokinetic profile and anti-cancer activity of fluorinated and iodinated photosensitizers (PSs), the 3-(1'-(

Topics: Animals; Cell Line, Tumor; Chlorophyll; Chlorophyll A; Male; Mice; Neoplasms; Photochemotherapy; Photosensitizing Agents

Photodynamic therapy (PDT) is considered as a promising therapeutic approach for clinical cancer treatment. However, the hypoxia of the tumor microenvironment leads to the low effect of single PDT. Here, a dual-photosensitizer nanoplatform based on near-infrared excitation orthogonal emission nanomaterials is constructed by introducing two kinds of photosensitizers into the nanosystem. Orthogonal emission upconversion nanoparticles (OE-UCNPs) were used as light conversion reagents to generate red emission under 980 nm irradiation and green emission under 808 nm irradiation. On the one hand, merocyanine 540 (MC540) is introduced as a photosensitizer (PS), which can absorb green light to generate reactive oxygen species (ROS) and trigger PDT for tumor treatment. On the other hand, another photosensitizer, chlorophyll a (Chla), which can be excited by red light, has also been introduced into the system to build a dual PDT nanotherapeutic platform. The introduction of photosensitizer Chla can synergistically increase ROS concentration to accelerate cancer cell apoptosis. Our research shows that this dual PDT nanotherapeutic platform combined with Chla has better therapeutic effects and effectively destroys cancer.

Topics: Chlorophyll A; Humans; Nanoparticles; Neoplasms; Photochemotherapy; Photosensitizing Agents; Reactive Oxygen Species; Tumor Microenvironment

Effective anti-cancer therapy is hurdled by the complicated extracellular and intracellular barriers, and thus a smart gene vector that can enable programmable gene delivery is highly demanded. Photo-manipulation of gene delivery processes features spatial and temporal precision, while majority of current strategies utilizes short-wavelength UV/visible light with poor tissue penetration or high-power-density near-infrared (NIR) light that would cause undesired heat damage. Herein, an ROS-degradable polycation was designed and co-delivered with a photosensitizer (PS), thus realizing photo-programmable gene delivery using far-red light (661 nm) at low optical power density (down to 5 mW cm

Topics: Animals; Antineoplastic Agents; Cell Death; Combined Modality Therapy; Cross-Linking Reagents; DNA; DNA Damage; Endocytosis; Endosomes; Gene Transfer Techniques; Hyaluronic Acid; Light; Male; Melanoma, Experimental; Mice, Inbred C57BL; Nanoparticles; Neoplasms; Pheophytins; Photochemotherapy; Polyethyleneimine; Reactive Oxygen Species; Tumor Suppressor Protein p53; Xenograft Model Antitumor Assays

A series of chlorophyll a-based chlorins conjugated with pyridyl or quinoxalyl group at different positions were synthesized, characterized and evaluated for their photodynamic effect in vitro. It was found that all the pyridyl and quinoxalyl chlorins showed promising photocytotoxicities but nontoxic without irradiation in HeLa cells, and the substituted types and positions had a significant influence on the photocytotoxicities of the chlorophyll a-based chlorins. All the chlorins with a pyridyl group at the C-D ring end exhibited relatively high photocytotoxicity as compared to those with 3(2)-pyridyl. Among them, compound 12 conjugated with a pyridyl group at its C12 position showed the best photodynamic effect in HeLa cells with an IC50 value of 0.033μM. These facts, associated with the relative high long wavelength absorptions of those chlorins may provide valuable ways to design and prepare promising photosensitizers for application in photodynamic therapy.

Topics: Chlorophyll; Chlorophyll A; HeLa Cells; Humans; Neoplasms; Photochemotherapy; Photosensitizing Agents; Porphyrins; Pyridines; Quinoxalines

Using stereoselective aldol-like condensation as a key methodology, a series of chlorophyll a-based long wavelength cationic chlorins were synthesized using methyl pyropheophorbide a (MPPa) and purpurin-18-N-methoxylimide methyl ester as starting materials. Such long wavelength cationic chlorins possess covalently linked cationic moieties (pyridinium or quinolinium) on the peripheral of their tetrapyrrole macrocycles. It was found that all long wavelength cationic chlorins showed their longest absorption maxima in the range of 712-763nm, making them potential photosensitizers in photodynamic therapy. The results of preliminary experiments probing in vitro photodynamic effects showed that the purpurinimide derivatives exhibit relatively high phototoxicity in HeLa cells as compared to MPPa derivatives.

Topics: Cell Survival; Chlorophyll; Chlorophyll A; HeLa Cells; Humans; Neoplasms; Photochemotherapy; Photosensitizing Agents; Porphyrins; Stereoisomerism

Two positional isomers of purpurinimide, 3-[1'-(3-iodobenzyloxyethyl)] purpurin-18-N-hexylimide methyl ester 4, in which the iodobenzyl group is present at the top half of the molecule (position-3), and a 3-(1'-hexyloxyethy)purpurin-18-N-(3-iodo-benzylimide)] methyl ester 5, where the iodobenzyl group is introduced at the bottom half (N-substitued cyclicimide) of the molecule, were derived from chlorophyll-a. The tumor uptake and phototherapeutic abilities of these isomers were compared with the pyropheophorbide analogue 1 (lead compound). These compounds were then converted into the corresponding 124I-labeled PET imaging agents with specific activity >1 Ci/micromol. Among the positional isomers 4 and 5, purpurinimide 5 showed enhanced imaging and therapeutic potential. However, the lead compound 1 derived from pyropheophorbide-a exhibited the best PET imaging and PDT efficacy. For investigating the overall lipophilicity of the molecule, the 3-O-hexyl ether group present at position-3 of purpurinimide 5 was replaced with a methyl ether substituent, and the resulting product 10 showed improved tumor uptake, but due to its significantly higher uptake in the liver, spleen, and other organs, a poor tumor contrast in whole-body tumor imaging was observed.

Topics: Animals; Anthraquinones; Chlorophyll; Chlorophyll A; Iodine Radioisotopes; Iodobenzenes; Isomerism; Mice; Neoplasms; Photochemotherapy; Photosensitizing Agents; Positron-Emission Tomography; Tissue Distribution

Topics: Chlorophyll; Chlorophyll A; Deodorants; Humans; Neoplasms