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Alternative Tumor-Targeting Strategies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
The chemical structures of porfimer sodium and temoporfin are based on the porphyrin and closely related chlorin structures (Figure 10.28), a group of naturally occurring intensely colored compounds whose name originates in the Greek word for purple (i.e., porphura). Molecules of this type perform biologically important roles in plants, animals, and bacteria, including photosynthesis. The porphyrins are tetrapyrrolic molecules, with the overall heterocyclic macrocycle known as a porphine. The basic porphine frame consists of four pyrrolic subunits linked on opposing sides through four methine (CH) bridges known as the meso-carbon atoms/positions. The resulting conjugated planar macrocycle may be substituted at the meso- or other positions. The related chlorin structure consists of three pyrroles and one pyrroline coupled through four =CH- linkages. Unlike porphin, the central aromatic ring structure of the porphyrins, a chlorin is predominantly aromatic but not through the entire circumference of the macrocyclic ring. The chlorophyll macrocycles that provide the central photosensitive pigments in the chloroplasts of plants and bacteria are magnesium-containing chlorins. For porphyrin-based PDT agents such as porfimer sodium and temoporfin, the excited state of the porphyrin molecules after illumination with light of an appropriate wavelength and energy, and the subsequent electron spin transfer to molecular oxygen, generate singlet oxygen atoms (i.e., free radicals) which exert the cytotoxic effect.
Photodynamic Therapy
Published in Glenn J. Jaffe, Paul Ashton, P. Andrew Pearson, Intraocular Drug Delivery, 2006
Preclinical studies using another chlorin, mono-L-aspartyl chlorin e6 (NPe6) have been conducted in rabbits and monkeys (34). PDT using Npe6 was performed in the monkey model of laser-induced CNV with dye doses ranging from 0.5 to 10 mg/kg and fluences from 7.5 to 225.0 J/cm2 (35). While successful occlusion was obtained at all dye doses, optimal parameters were judged to involve treatment 5–30 minutes following dye injection with dye doses of either 0.5 or 1.0 mg/kg. Higher fluences were required with the lower photosensitizer dose and with increasing time between injection and irradiance. Histologic analysis seven days after treatment revealed numerous vacuoles in the cytoplasm of RPE cells, but the neurosensory retina remained intact.
Topical Photodynamic Therapy for Skin Diseases: Current Status of Preclinical and Clinical Research, Nanocarriers and Physical Methods for Photosensitizer Delivery
Published in Andreia Ascenso, Sandra Simões, Helena Ribeiro, Carrier-Mediated Dermal Delivery, 2017
Fabíola Silva Garcia Praça, Patricia Mazureki Campos, Josimar O. Eloy, Raquel Petrilli, Maria Vitória Lopes Badra Bentley, Wanessa Silva Garcia Medina
Chlorins are reduced forms of porphyrins that are attracting attention in PDT field due to the pronounced absorption at 650-900 nm and because of the ability to sensitize singlet oxygen in high quantum yields and low remaining toxicity in the dark [36–39]. Furthermore, chlorin absorption bands in the UV, blue region and red visible, the latter usually in the range of red at 640-700 nm, can be modified by chelated metal ions [40,41]. As a consequence of their low green region absorption, chlorins exhibit the green color that is related to the name in greek “chloros” [40]. Basically, a chlorin consists of a large heterocyclic aromatic compound with a core of three pyrroles and one reduced pyrrole ring that are coupled by methine linkages. One important example is the chlorophyll presence in plants that consists of a naturally occurring magnesium chlorin [42]. Since the 1980s, chlorins have been used in PDT and many derivatives were developed [42]; however, only the m-tetra(hydroxyphenyl) chlorin (m-THPC or termoporfirin, marketed as Foscan®) has been approved in Europe for the treatment of head and neck squamous cell carcinomas [43]. Gupta and colleagues (1999) were the first to study the effect of topical application of m-THPC using PDT for basal cell carcinoma and Bowen’s disease in humans. Authors observed the pathological clearance in nine out of the 28 patients under treatment [44]. With the purpose of improved efficacy and decreased side effects, topical delivery of Foscan® delivery systems can be applied [45] and will be further discussed in the section “Nanocarriers for improved dermal skin delivery of photosensitizers in PDT”.
Laser-triggered intelligent drug delivery and anti-cancer photodynamic therapy using platelets as the vehicle
Published in Platelets, 2023
Qi-Rui Li, Hua-Zhen Xu, Rong-Cheng Xiao, Bin Liu, Tian-Qi Ma, Ting-Ting Yu, Liu-Gen Li, Mei-Fang Wang, Li Zhao, Xiao Chen, Tong-Fei Li
Platelets are abundant, tiny, with long circulation effects, and thereby are excellent cellular carriers easily accessible to transport drugs to the neovascularization of tumors [1–3]. Platelet activation leads to the adhesion to the vascular endothelium and releasing the internal granules [4–8], which is important for drug delivery [9,10]. Consequently, controlled regulation of platelet activation holds potential for targeted drug delivery. Chlorin e6 (Ce6) is frequently used as a photosensitizing drug with low toxicity, fluorescent tracer, which could be activated by laser irradiation to generate reactive oxygen species (ROS) for photoselective cellular modulation or destroying [11,12]. However, few studies have concerned the effect of photodynamic effects on platelets so far. There is evidence suggesting that oxidative stress can induce platelet activation [13–16]. Thus, platelets loaded with Ce6 are presumed to be activated by laser irradiation to release the loaded photosensitizer, achieving laser-triggered drug delivery.
3D self-assembled nanocarriers for drug delivery
Published in Drug Metabolism Reviews, 2023
Hossein Karballaei Mirzahosseini, Mojgan Sheikhi, Farhad Najmeddin, Mehrnoosh Shirangi, Mojtaba Mojtahedzadeh
Finally, the uses of CNTs in the microelectronics industry are very fascinating. The development of thin film transistors (TFTs) based on self-assembled, aligned, semiconducting CNT arrays (CNT-TFT) was studied by Engel et al. (2008). The films in that instance were created using a solution of pre-separated (99% purely) semiconducting CNTs, which self-assembled into micron-wide strips of arrays of precisely aligned CNT films that covered the whole nanodevice (chip). The constructed CNT-TFTs produced strong photocurrents (exhibiting both high driving currents and huge on/off current ratios) and were both photo- and electroluminescent. Zhu et al. (2004) developed a novel long-circulating SWCNT-based therapeutic strategy to administer chlorin e6 (Ce6). A well-known photosensitizer with high near-fluorescence, SWCNT-based theranostic technology, offers a lot of potential for imaging-guided PTT/PDT combo treatment for cancer. Another illustration demonstrates the potential for using chirality-selective affinity between CNTs and a gel composed of various surfactants in the chromatographic separation of different components (Yomogida et al. 2016). This study identifies the chiral-angle selectivity and diameter selectivity. Given that the chirality of nanotubes is controlled by the chiral angle and diameter, combining these various selectivities yields high-resolution single-chirality separation with milligram-scale throughput and remarkable purity. Separated single-chirality nanotubes were used to provide superior biological imaging results for mouse vascular imaging (Figure 11).
Emerging theranostics to combat cancer: a perspective on metal-based nanomaterials
Published in Drug Development and Industrial Pharmacy, 2022
Tejas Girish Agnihotri, Shyam Sudhakar Gomte, Aakanchha Jain
A light-responsive drug delivery system enables the temporal and spatial-based release of therapeutic agents [69]. Light can be concentrated very strongly to produce a localized response, allowing for precise spatiotemporal control of therapeutic release. Using a variety of easily available light sources, light-responsive drug structures can be disseminated throughout the body yet only remain active within the specific tissue or organ [70]. Light is a fascinating external stimulus used for controlled drug release because, with an on/off switching pulsatile behavior, drug was released with high spatial and temporal precision [71]. Light-responsive DDS is widely employed in photodynamic therapy which uses light, tissue oxygen, and photoactivable sensitizer. PDT involves the injection of a photosensitizer intravenously, and light-mediated activation is responsible for converting tissue oxygen to radical oxygen species (ROS) [65]. In this regard, Zhang et al. [72] reported light-responsive liposomes for cancer theranostic applications. Chlorin e6 acts as a photosensitizer, which upon interaction with a laser, induced hypoxia, and resulted in liposomal disassembly and elicited anticancer activity. Hao et al. [73] prepared NIR responsive 5-FU and indocyanine green-loaded monomethoxy–polyethylene glycol–polycaprolactone NPs for the skin cancer management. Further, hyaluronic acid was used to integrate microneedle system. The prepared microneedle system had good penetration ability via skin and release pattern of the drug was regulated by NIR light. It was proved to be efficient delivery system for the management of skin cancer. In addition, Liu et al. prepared PEG functionalized mesoporous silica (MS) coated with single-walled CNTs (SWCNTs) and employed it as image-guided therapy in cancer applications. It was observed that under stimulation of NIR light, photothermal triggered drug release was observed from DOX-encapsulated SWCNTs modified with mesoporous silica–PEG from inside cells resulting in an enhanced cancer-killing effect. This work provided a theranostic platform that helped to load therapeutic agent and greater efficiency and simultaneously, offered external NIR stimulation, and was used as an imaging agent in cancer therapy [74]. In another research work, Li et al. reported mesoporous silica-coated CNTs to give phototherapy combined drug release initiated by NIR laser excitation [75].