Potent PBS/Polysorbate-Soluble Transplatin-Derived Porphyrin-Based Photosensitizers for Photodynamic Therapy

Schneider, Lukas; Kalt, Martina; Larocca, Michele; Babu, Vommina V. Suresh; Spingler, Bernhard

doi:10.1021/acs.inorgchem.1c00415

Cited by 13 publications

(14 citation statements)

References 37 publications

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“…MCTSs treated with 1b and subsequent irradiation with light of 630 nm started dissolving on day three visible in the inflation of the MCTSs to 233% of the initial size followed by a steady decrease in size. This shows that 1b is not just decreasing the growth rate of the MCTSs like cisplatin [40] , but Because MCTSs also simulate tumour hypoxia and proliferation gradients to the centre [51,52] , the observed effectivity in HeLa MCTSs indicated a possible efficiency under hypoxic conditions. To test this hypothesis, the photocytotoxicity determination for compounds 1a and b a 1b in monolayer HeLa cells was repeated under hypoxic conditions (Tab.…”

Section: Photocytotoxicitymentioning

confidence: 87%

BODIPY-Based Photothermal Agents for Cancer Treatment

Schneider

Kalt

Koch

et al. 2022

Preprint

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Here we report six novel, easily accessible BODIPY‐based agents for cancer treatment. In contrast to established photodynamic therapy (PDT) agents, these BODIPY-based compounds show additional photothermal activity and their cytotoxicity is not dependent on the generation of reactive oxygen species (ROS). The agents show high photocytotoxicity upon irradiation with light and low dark toxicity in different cancer cell lines in 2D culture as well as in 3D multicellular tumour spheroids (MCTSs). The ratio of dark to light toxicity (phototoxic index, PI) of these agents reaches striking values exceeding 830ʹ000 after irradiation with energetically low doses of light at 630 nm. The oxygen‐dependent mechanism of action (MOA) of established photosensitizers (PSs) hampers effective clinical deployment of these agents. Under hypoxic conditions (0.2% O2), which are known to limit the efficiency of conventional PSs in solid tumours, a PI of 360ʹ000 was observed, indicating an oxygen-independent photothermal MOA. Both PI values are the highest reported to date. We anticipate that small molecule agents with a photothermal MOA, such as BODIPY-based compounds, may overcome this barrier and provide a new avenue to cancer therapy.

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Section: Photocytotoxicitymentioning

confidence: 87%

BODIPY-Based Photothermal Agents for Cancer Treatment

Schneider

Kalt

Koch

et al. 2022

Preprint

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“…As a result of cell attachment interruption on the surface, the liquid overlay culture system facilitates an increase in cell–cell interaction and promotes cell aggregation, leading to the spontaneous formation of spheroids above the non-adherent surface [ 32 ]. For example, a recent study by Schnieder et al [ 34 ] produced HeLa MCTS by the liquid overlay method based on agarose-coated 96-well plates to investigate the phototoxicity of tetraplatinated (metallo) porphyrin-based PS. The study reported a phototoxic index (PI) of 6030 in HeLa cells [ 34 ].…”

Section: Methods For 3d Tumor Generationmentioning

confidence: 99%

“…For example, a recent study by Schnieder et al [ 34 ] produced HeLa MCTS by the liquid overlay method based on agarose-coated 96-well plates to investigate the phototoxicity of tetraplatinated (metallo) porphyrin-based PS. The study reported a phototoxic index (PI) of 6030 in HeLa cells [ 34 ]. Similarly, Karges et al [ 35 ] cultured HeLa MCTS using the liquid overlay technique and evaluated the phototoxic effect of Ru(II) polypyridine complexes with (E,E′)-4,4′-bisstyryl-2,2′-bipyridine ligand [ 35 ].…”

Section: Methods For 3d Tumor Generationmentioning

confidence: 99%

“…The hydrophilic structure allows for large amounts of water to be absorbed and retained [ 37 ]. They can be designed with a wide range of compositions, biophysical properties, and biological functions, allowing them to mimic many of the characteristics of natural ECMs [ 31 , 34 ]. Natural biomaterials composed of polysaccharide (amylose, cellulose, alginate, chitosan, or hyaluronic acid), peptide (collagen or gelatin), nucleic acid, or polyhydroxyalkanoates are used to design the 3D culture system of cancer cells [ 37 , 39 ].…”

Section: Methods For 3d Tumor Generationmentioning

confidence: 99%

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Photodynamic Therapy-Mediated Immune Responses in Three-Dimensional Tumor Models

Nkune

Simelane

Montaseri

et al. 2021

IJMS

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Photodynamic therapy (PDT) is a promising non-invasive phototherapeutic approach for cancer therapy that can eliminate local tumor cells and produce systemic antitumor immune responses. In recent years, significant efforts have been made in developing strategies to further investigate the immune mechanisms triggered by PDT. The majority of in vitro experimental models still rely on the two-dimensional (2D) cell cultures that do not mimic a three-dimensional (3D) cellular environment in the human body, such as cellular heterogeneity, nutrient gradient, growth mechanisms, and the interaction between cells as well as the extracellular matrix (ECM) and therapeutic resistance to anticancer treatments. In addition, in vivo animal studies are highly expensive and time consuming, which may also show physiological discrepancies between animals and humans. In this sense, there is growing interest in the utilization of 3D tumor models, since they precisely mimic different features of solid tumors. This review summarizes the characteristics and techniques for 3D tumor model generation. Furthermore, we provide an overview of innate and adaptive immune responses induced by PDT in several in vitro and in vivo tumor models. Future perspectives are highlighted for further enhancing PDT immune responses as well as ideal experimental models for antitumor immune response studies.

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“…An important parameter to evaluate the effect of PSs is the phototoxic index (p.i. ), i.e., the ratio of dark to light toxicity [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. Reducing the lipophilicity and minimizing aggregation of the planar PS, for example by PEGylation, plays a critical role for improving PDT therapeutic efficiency and improving the p.i.…”

Section: Introductionmentioning

confidence: 99%

Low-Dose Near-Infrared Light-Activated Mitochondria-Targeting Photosensitizers for PDT Cancer Therapy

Giger

Schneider

et al. 2022

IJMS

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Phthalocyanines (Pcs) are promising candidates for photodynamic therapy (PDT) due to their absorption in the phototherapeutic window. However, the highly aromatic Pc core leads to undesired aggregation and decreased reactive oxygen species (ROS) production. Therefore, short PEG chain functionalized A3B type asymmetric Pc photosensitizers (PSs) were designed in order to decrease aggregation and increase the aqueous solubility. Here we report the synthesis, characterization, optical properties, cellular localization, and cytotoxicity of three novel Pc-based agents (LC31, MLC31, and DMLC31Pt). The stepwise functionalization of the peripheral moieties has a strong effect on the distribution coefficient (logP), cellular uptake, and localization, as well as photocytotoxicity. Additional experiments have revealed that the presence of the malonic ester moiety in the reported agent series is indispensable in order to induce photocytotoxicity. The best-performing agent, MLC31, showed mitochondrial targeting and an impressive phototoxic index (p.i.) of 748 in the cisplatin-resistant A2780/CP70 cell line, after a low-dose irradiation of 6.95 J/cm2. This is the result of a high photocytotoxicity (IC50 = 157 nM) upon irradiation with near-infrared (NIR) light, and virtually no toxicity in the dark (IC50 = 117 μM). Photocytotoxicity was subsequently determined under hypoxic conditions. Additionally, a preliminarily pathway investigation of the mitochondrial membrane potential (MMP) disruption and induction of apoptosis by MLC31 was carried out. Our results underline how agent design involving both hydrophilic and lipophilic peripheral groups may serve as an effective way to improve the PDT efficiency of highly aromatic PSs for NIR light-mediated cancer therapy.

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Potent PBS/Polysorbate-Soluble Transplatin-Derived Porphyrin-Based Photosensitizers for Photodynamic Therapy

Cited by 13 publications

References 37 publications

BODIPY-Based Photothermal Agents for Cancer Treatment

BODIPY-Based Photothermal Agents for Cancer Treatment

Photodynamic Therapy-Mediated Immune Responses in Three-Dimensional Tumor Models

Low-Dose Near-Infrared Light-Activated Mitochondria-Targeting Photosensitizers for PDT Cancer Therapy

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