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15 pages, 7590 KiB

Open AccessArticle

Antitumor Effects of Pegylated Zinc Protoporphyrin-Mediated Sonodynamic Therapy in Ovarian Cancer

by Jia Li, Zheng Hu, Jiwei Zhu, Xin Lin, Xu Gao and Guixiang Lv

Pharmaceutics 2023, 15(9), 2275; https://doi.org/10.3390/pharmaceutics15092275 - 04 Sep 2023

Viewed by 892

Sonodynamic therapy (SDT) induces reactive oxygen species (ROS) to kill tumor cells. Heme oxygenase-1 (HO-1), as an important antioxidant enzyme, resists killing by scavenging ROS. Zinc protoporphyrin (ZnPP) not only effectively inhibits HO-1 activity, but also becomes a potential sonosensitizer. However, its poor [...] Read more.

Sonodynamic therapy (SDT) induces reactive oxygen species (ROS) to kill tumor cells. Heme oxygenase-1 (HO-1), as an important antioxidant enzyme, resists killing by scavenging ROS. Zinc protoporphyrin (ZnPP) not only effectively inhibits HO-1 activity, but also becomes a potential sonosensitizer. However, its poor water solubility limits its applications. Herein, we developed an improved water-soluble method. It was proved that pegylated zinc protoporphyrin-mediated SDT (PEG-ZnPP-SDT) could significantly enhance ROS production by destroying the HO-1 antioxidant system in ovarian cancer. Increased ROS could cause mitochondrial membrane potential collapse, release cytochrome c from mitochondria to the cytoplasm, and trigger the mitochondrial–caspase apoptotic pathway. In conclusion, our results demonstrated that PEG-ZnPP-SDT, as a novel sonosensitizer, could improve the antitumor effects by destroying the HO-1 antioxidant system. It provided a new therapeutic strategy for SDT to treat cancers, especially those with higher HO-1 expression. Full article

(This article belongs to the Special Issue Advances in Phototherapy and Sonodynamic Therapy)

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13 pages, 4320 KiB

Open AccessArticle

Curcumin–Triterpene Type Hybrid as Effective Sonosensitizers for Sonodynamic Therapy in Oral Squamous Cell Carcinoma

by Katarzyna Sowa-Kasprzak, Małgorzata Józkowiak, Dorota Olender, Anna Pawełczyk, Hanna Piotrowska-Kempisty and Lucjusz Zaprutko

Pharmaceutics 2023, 15(7), 2008; https://doi.org/10.3390/pharmaceutics15072008 - 23 Jul 2023

Cited by 1 | Viewed by 1116

Abstract

Sonodynamic therapy (SDT) is a non-invasive therapeutic modality in cancer treatment that combines low-intensity ultrasound (US) and sonosensitizers. Tumor cells are destroyed through the synergistic effects of ultrasound and a chemical sonosensitizer. This study focused on the synthesis and in vitro evaluation of [...] Read more.

Sonodynamic therapy (SDT) is a non-invasive therapeutic modality in cancer treatment that combines low-intensity ultrasound (US) and sonosensitizers. Tumor cells are destroyed through the synergistic effects of ultrasound and a chemical sonosensitizer. This study focused on the synthesis and in vitro evaluation of the sonodynamic effect of natural curcumin, triterpene oleanolic acid, and their semi-synthetic derivatives on tongue cancer SCC-25 and hypopharyngeal FaDu cell lines. The combination of the tested compounds with sonication showed a synergistic increase in cytotoxicity. In the group of oleanolic acid derivatives, oleanoyl hydrogen succinate (6) showed the strongest cytotoxic effect both in the SCC-25 and FaDu cell lines. Comparing curcumin (4) and its pyrazole derivative (5), curcumin showed a better cytotoxic effect on SCC-25 cells, while curcumin pyrazole was more potent on FaDu cells. The highest sonotherapeutic activity, compared to its individual components, was demonstrated by a structural linker mode hybrid containing both curcumin pyrazole-oleanoyl hydrogen succinate units within one complex molecule (7). This study can be beneficial in the context of new perspectives in the search for effective sonosensitizers among derivatives of natural organic compounds. Full article

(This article belongs to the Special Issue Advances in Phototherapy and Sonodynamic Therapy)

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17 pages, 8966 KiB

Open AccessArticle

Multi-Wavelength Photoacoustic Temperature Feedback Based Photothermal Therapy Method and System

by Yiming Ma, Yang Liu, Zhigang Lei, Zezheng Qin, Yi Shen and Mingjian Sun

Pharmaceutics 2023, 15(2), 555; https://doi.org/10.3390/pharmaceutics15020555 - 07 Feb 2023

Cited by 1 | Viewed by 1346

Abstract

Photothermal therapy (PTT) is a new type of tumor treatment technology that is noninvasive, repeatable, and does not involve radiation. Owing to the lack of real-time and accurate noninvasive temperature measurement technology in current PTT surgical procedures, empirical and open-loop treatment laser power [...] Read more.

Photothermal therapy (PTT) is a new type of tumor treatment technology that is noninvasive, repeatable, and does not involve radiation. Owing to the lack of real-time and accurate noninvasive temperature measurement technology in current PTT surgical procedures, empirical and open-loop treatment laser power control mode inevitably leads to overtreatment. Thermal radiation causes irreversible damage to normal tissue around cancer tissue and seriously affects the therapeutic effect of PTT and other therapies conducted at the same time. Therefore, real-time measurement and control of the temperature and thermal damage of the therapeutic target are critical to the success of PTT. To improve the accuracy and safety of PTT, we propose a multi-wavelength photoacoustic (PA) temperature feedback based PTT method and system. PA thermometry information at different wavelengths is mutually corrected, and the therapeutic light dose is regulated in real time to accurately control the treatment temperature. The experimental results on the swine blood sample confirm that the proposed method can realize real-time temperature measurement and control of the target area with an accuracy of 0.56 °C and 0.68 °C, demonstrating its good prospects for application. Full article

(This article belongs to the Special Issue Advances in Phototherapy and Sonodynamic Therapy)

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17 pages, 3588 KiB

Open AccessArticle

Influence of Green Synthesized Zinc Oxide Nanoparticles on Molecular Interaction and Comparative Binding of Azure Dye with Chymotrypsin: Novel Nano-Conjugate for Cancer Phototherapy

by Amit Singh, Pankaj Kumar, Niloy Sarkar and Mahima Kaushik

Pharmaceutics 2023, 15(1), 74; https://doi.org/10.3390/pharmaceutics15010074 - 26 Dec 2022

Cited by 3 | Viewed by 1456

Abstract

Till date, different types of conventional drugs have been used to fight tumors. However, they have significant flaws, including their usage being constrained because of their low bioavailability, poor supply, and serious side effects. The modern combination therapy has been viewed as a [...] Read more.

Till date, different types of conventional drugs have been used to fight tumors. However, they have significant flaws, including their usage being constrained because of their low bioavailability, poor supply, and serious side effects. The modern combination therapy has been viewed as a potent strategy for treating serious illnesses, including cancer-type feared diseases. The nanoparticles are a promising choice for cancer therapeutic and diagnostic applications because of their fascinating optoelectronic and physicochemical features. Among the metallic nanoparticles, Zinc oxide nanoparticles possess interesting physicochemical and anti-cancer characteristics, such as ROS generation, high retention, enhanced permeability etc., making them attractive candidates for the treatment and diagnosis of cancer. Zinc oxide nanoparticles showed anti-cancer property via excessive reactive oxygen species (ROS) production, and by the destruction of mitochondrial membrane. Here, we have synthesized organic/inorganic hybrid nanosystem composed of chymotrypsin protein (Chymo) with AzureC (AzC) conjugated with Zinc oxide nanoparticles (ZnONPs). The conjugation of AzureC with ZnONPs was confirmed by transmission electron microscopy (TEM), zeta potential, and dynamic light scattering (DLS) experiment. The interaction of Chymo with AzC alone and AzC-ZnONPs was investigated, and it was observed that the interaction was enhanced in the presence of ZnONPs, which was concluded by the results obtained from different spectroscopic techniques such as UV-Visible spectroscopy, fluorescence spectroscopy and circular dichroism in combination with molecular docking. UV-Visible spectroscopic studies and the corresponding binding parameters showed that the binding of AzC-ZnONPs complex with Chymo is much higher than that of AzC alone. Moreover, the fluorescence measurement showed enhancement in static quenching during titration of Chymo with AzC-ZnONPs as compared to dye alone. In addition to this, circular dichroism results show that the dye and dye-NPs conjugate do not cause much structural change in α-Chymo. The molecular docking and thermodynamic studies showed the predominance of hydrogen bonding, Van der Waal force, and hydrophobic forces during the interactions. After correlation of all the data, interaction of Chymo with AzC-ZnONPs complex showed strong interaction as compared to dye alone. The moderate binding with chymo without any alteration in the structure makes it desirable for the distribution and pharmacokinetics. In addition, the in vitro cytotoxicity of the AzC-ZnONPs was demonstrated on A-549 adenocarcinoma cell line. Our findings from physiochemical investigations suggested that the chymotrypsin coated AzC conjugated ZnONPs could be used as the novel nanoconjugates for various cancer phototherapies. Full article

(This article belongs to the Special Issue Advances in Phototherapy and Sonodynamic Therapy)

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19 pages, 4386 KiB

Open AccessArticle

Thermo and Photoresponsive Emulgel Loaded with Copaifera reticulata Ducke and Chlorophylls: Rheological, Mechanical, Photodynamic and Drug Delivery Properties in Human Skin

by Katieli da Silva Souza Campanholi, Ranulfo Combuca da Silva Junior, Jonas Marcelo Jaski, Jéssica Bassi da Silva, Mariana Carla de Oliveira, Rafaela Said dos Santos, Magali Soares dos Santos Pozza, Lidiane Vizioli de Castro-Hoshino, Mauro Luciano Baesso, Lucio Cardozo-Filho, Marcos Luciano Bruschi and Wilker Caetano

Pharmaceutics 2022, 14(12), 2798; https://doi.org/10.3390/pharmaceutics14122798 - 14 Dec 2022

Cited by 6 | Viewed by 1535

Abstract

Recently, the number of new cases of cutaneous leishmaniasis has been of concern among health agencies. Research that offers new therapeutic alternatives is advantageous, especially those that develop innovative drugs. Therefore, this paper presents the incorporation of Copaifera reticulata Ducke and chlorophyll extract [...] Read more.

Recently, the number of new cases of cutaneous leishmaniasis has been of concern among health agencies. Research that offers new therapeutic alternatives is advantageous, especially those that develop innovative drugs. Therefore, this paper presents the incorporation of Copaifera reticulata Ducke and chlorophyll extract into Pluronic^®® F127 and Carbopol gels, under optimized polymer quantities. The chlorophyll extract (rich in photosensitizing compounds) was obtained by continuous-flow pressurized liquid extraction (PLE), a clean, environmentally friendly method. The system aims to act as as a leishmanicidal, cicatrizant, and antibiotic agent, with reinforcement of the photodynamic therapy (PDT) action. Rheological and mechanical analyses, permeation studies and bioadhesiveness analyses on human skin, and PDT-mediated activation of Staphylococcus aureus were performed. The emulgels showed gelation between 13° and 15 °C, besides pseudoplastic and viscoelastic properties. Furthermore, the systems showed transdermal potential, by releasing chlorophylls and C. reticulata Ducke into the deep layers of human skin, with good bioadhesive performance. The application of PDT reduced three logarithmic colony-forming units of S. aureus bacteria. The results support the potential of the natural drug for future clinical trials in treating wounds and cutaneous leishmania. Full article

(This article belongs to the Special Issue Advances in Phototherapy and Sonodynamic Therapy)

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20 pages, 8713 KiB

Open AccessArticle

CD44-Receptor Targeted Gold-Doxorubicin Nanocomposite for Pulsatile Chemo-Photothermal Therapy of Triple-Negative Breast Cancer Cells

by Dnyaneshwar Kalyane, Suryanarayana Polaka, Nupur Vasdev and Rakesh Kumar Tekade

Pharmaceutics 2022, 14(12), 2734; https://doi.org/10.3390/pharmaceutics14122734 - 06 Dec 2022

Cited by 4 | Viewed by 1738

Abstract

This study reports the CD44 receptor-targeted gold-doxorubicin nanocomposite (_TGNC-DOX) for pulsatile chemo-photothermal therapy of triple-negative breast cancer (TNBC). The developed _TGNC-DOX was nanometric, having a particle size of 71.34 ± 3.66 nm. The doxorubicin was loaded by electrostatic interaction with [...] Read more.

This study reports the CD44 receptor-targeted gold-doxorubicin nanocomposite (_TGNC-DOX) for pulsatile chemo-photothermal therapy of triple-negative breast cancer (TNBC). The developed _TGNC-DOX was nanometric, having a particle size of 71.34 ± 3.66 nm. The doxorubicin was loaded by electrostatic interaction with high entrapment and loading efficiency (>75%). _TGNC-DOX showed potent photothermal response and reversible photothermal stability following irradiation with 808 nm NIR laser irradiation. Further, _TGNC-DOX showed laser-responsive and pH-dependent drug release behavior suggesting its suitability for chemo-photothermal therapy, specifically at the tumor microenvironment site. Cellular viability, cellular uptake, ROS generation, and apoptosis assays suggested selective localization of _TGNC-DOX in cancer cells that showed a significant cytotoxic effect against MDA-MB-231 breast cancer cells. Moreover, the developed _TGNC-DOX showed ferroptosis in MDA-MB-231 cells. The event of _TGNC-DOX-mediated thermal ablation is marked by a significant generation of reactive oxygen species (ROS) and apoptosis, as affirmed by flow cytometry. NIR-808 laser-responsive photothermal therapy of cancer cells was found to be more effective than without NIR-808 laser-treated cells, suggesting the fundamental role of photothermal ablation. The outcome concludes developed _TGNC-DOX is a novel and potential tool to mediate laser-guided chemo-photothermal ablation treatment of cancer cells. Full article

(This article belongs to the Special Issue Advances in Phototherapy and Sonodynamic Therapy)

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23 pages, 6744 KiB

Open AccessArticle

Para-N-Methylpyridinium Pyrenes: Impact of Positive Charge on ds-DNA/RNA and Protein Recognition, Photo-Induced Bioactivity, and Intracellular Localisation

by Marta Košćak, Isabela Pehar, Ksenija Božinović, Goutam Kumar Kole, Sandra Sobočanec, Iva I. Podgorski, Marija Pinterić, Klaus Müller-Buschbaum, Dragomira Majhen, Ivo Piantanida and Todd B. Marder

Pharmaceutics 2022, 14(11), 2499; https://doi.org/10.3390/pharmaceutics14112499 - 17 Nov 2022

Cited by 1 | Viewed by 1337

Abstract

The 2- and 2,7- substituted para-N-methylpyridinium pyrene cations show high-affinity intercalation into ds-DNAs, whereas their non-methylated analogues interacted with ds-DNA/RNA only in the protonated form (at pH 5), but not at physiological conditions (pH 7). The fluorescence from non-methylated analogues was strongly [...] Read more.

The 2- and 2,7- substituted para-N-methylpyridinium pyrene cations show high-affinity intercalation into ds-DNAs, whereas their non-methylated analogues interacted with ds-DNA/RNA only in the protonated form (at pH 5), but not at physiological conditions (pH 7). The fluorescence from non-methylated analogues was strongly dependent on the protonation of the pyridines; consequently, they act as fluorescence ratiometric probes for simultaneous detection of both ds-DNA and BSA at pH 5, relying on the ratio between intensities at 420 nm (BSA specific) and 520 nm (DNA specific), whereby exclusively ds-DNA sensing could be switched-off by adjustment to pH 7. Only methylated, permanently charged pyrenes show photoinduced cleavage of circular DNA, attributed to pyrene-mediated irradiation-induced production of singlet oxygen. Consequently, the moderate toxicity of these cations against human cell lines is strongly increased upon irradiation. Detailed studies revealed increased total ROS production in cells treated by the compounds studied, accompanied by cell swelling and augmentation of cellular complexity. The most photo-active 2-para-N-methylpyridinium pyrene showed significant localization at mitochondria, its photo-bioactivity likely due to mitochondrial DNA damage. Other derivatives were mostly non-selectively distributed between various cytoplasmic organelles, thus being less photoactive. Full article

(This article belongs to the Special Issue Advances in Phototherapy and Sonodynamic Therapy)

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Review

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25 pages, 1586 KiB

Open AccessReview

Recent Studies in Photodynamic Therapy for Cancer Treatment: From Basic Research to Clinical Trials

by Tae Eun Kim and Ji-Eun Chang

Pharmaceutics 2023, 15(9), 2257; https://doi.org/10.3390/pharmaceutics15092257 - 31 Aug 2023

Cited by 12 | Viewed by 2223

Abstract

Photodynamic therapy (PDT) is an emerging and less invasive treatment modality for various types of cancer. This review provides an overview of recent trends in PDT research, ranging from basic research to ongoing clinical trials, focusing on different cancer types. Lung cancer, head [...] Read more.

Photodynamic therapy (PDT) is an emerging and less invasive treatment modality for various types of cancer. This review provides an overview of recent trends in PDT research, ranging from basic research to ongoing clinical trials, focusing on different cancer types. Lung cancer, head and neck cancer, non-melanoma skin cancer, prostate cancer, and breast cancer are discussed in this context. In lung cancer, porfimer sodium, chlorin e6, and verteporfin have shown promising results in preclinical studies and clinical trials. For head and neck cancer, PDT has demonstrated effectiveness as an adjuvant treatment after surgery. PDT with temoporfin, redaporfin, photochlor, and IR700 shows potential in early stage larynx cancer and recurrent head and neck carcinoma. Non-melanoma skin cancer has been effectively treated with PDT using methyl aminolevulinate and 5-aminolevulinic acid. In prostate cancer and breast cancer, PDT research is focused on developing targeted photosensitizers to improve tumor-specific uptake and treatment response. In conclusion, PDT continues to evolve as a promising cancer treatment strategy, with ongoing research spanning from fundamental investigations to clinical trials, exploring various photosensitizers and treatment combinations. This review sheds light on the recent advancements in PDT for cancer therapy and highlights its potential for personalized and targeted treatments. Full article

(This article belongs to the Special Issue Advances in Phototherapy and Sonodynamic Therapy)

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18 pages, 652 KiB

Open AccessReview

Advances in the Application of Preclinical Models in Photodynamic Therapy for Tumor: A Narrative Review

by Rong Yu, Ewetse Paul Maswikiti, Yang Yu, Lei Gao, Chenhui Ma, Huanhuan Ma, Xiaobo Deng, Na Wang, Bofang Wang and Hao Chen

Pharmaceutics 2023, 15(1), 197; https://doi.org/10.3390/pharmaceutics15010197 - 05 Jan 2023

Cited by 4 | Viewed by 1555

Abstract

Photodynamic therapy (PDT) is a non-invasive laser light local treatment that has been utilized in the management of a wide variety of solid tumors. Moreover, the evaluation of efficacy, adverse reactions, the development of new photosensitizers and the latest therapeutic regimens are inseparable [...] Read more.

Photodynamic therapy (PDT) is a non-invasive laser light local treatment that has been utilized in the management of a wide variety of solid tumors. Moreover, the evaluation of efficacy, adverse reactions, the development of new photosensitizers and the latest therapeutic regimens are inseparable from the preliminary exploration in preclinical studies. Therefore, our aim was to better comprehend the characteristics and limitations of these models and to provide a reference for related research. Methods: We searched the databases, including PubMed, Web of Science and Scopus for the past 25 years of original research articles on the feasibility of PDT in tumor treatment based on preclinical experiments and animal models. We provided insights into inclusion and exclusion criteria and ultimately selected 40 articles for data synthesis. Results: After summarizing and comparing the methods and results of these studies, the experimental model selection map was drawn. There are 7 main preclinical models, which are used for different research objectives according to their characteristics. Conclusions: Based on this narrative review, preclinical experimental models are crucial to the development and promotion of PDT for tumors. The traditional animal models have some limitations, and the emergence of organoids may be a promising new insight. Full article

(This article belongs to the Special Issue Advances in Phototherapy and Sonodynamic Therapy)

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16 pages, 1241 KiB

Open AccessReview

The “Light Knife” for Gastric Cancer: Photodynamic Therapy

by Haiyun Wang, Maswikiti Paul Ewetse, Chenhui Ma, Weigao Pu, Bo Xu, Puyi He, Yunpeng Wang, Jingyu Zhu and Hao Chen

Pharmaceutics 2023, 15(1), 101; https://doi.org/10.3390/pharmaceutics15010101 - 28 Dec 2022

Cited by 4 | Viewed by 2399

Abstract

Photodynamic therapy (PDT) has been used clinically to treat cancer for more than 40 years. Some solid tumors, including esophageal cancer, lung cancer, head and neck cancer, cholangiocarcinoma, and bladder cancer, have been approved for and managed with PDT in many countries globally. [...] Read more.

Photodynamic therapy (PDT) has been used clinically to treat cancer for more than 40 years. Some solid tumors, including esophageal cancer, lung cancer, head and neck cancer, cholangiocarcinoma, and bladder cancer, have been approved for and managed with PDT in many countries globally. Notably, PDT for gastric cancer (GC) has been reported less and is not currently included in the clinical diagnosis and treatment guidelines. However, PDT is a potential new therapeutic modality used for the management of GC, and its outcomes and realization are more and more encouraging. PDT has a pernicious effect on tumors at the irradiation site and can play a role in rapid tumor shrinkage when GC is combined with cardiac and pyloric obstruction. Furthermore, because of its ability to activate the immune system, it still has a specific effect on systemic metastatic lesions, and the adverse reactions are mild. In this Review, we provide an overview of the current application progress of PDT for GC; systematically elaborate on its principle, mechanism, and the application of a new photosensitizer in GC; and focus on the efficacy of PDT in GC and the prospect of combined use with other therapeutic methods to provide a theoretical basis for clinical application. Full article

(This article belongs to the Special Issue Advances in Phototherapy and Sonodynamic Therapy)

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26 pages, 4466 KiB

Open AccessReview

Enhancing the Efficiency of Mild-Temperature Photothermal Therapy for Cancer Assisting with Various Strategies

by Pei Wang, Biaoqi Chen, Yunyan Zhan, Lianguo Wang, Jun Luo, Jia Xu, Lilin Zhan, Zhihua Li, Yuangang Liu and Junchao Wei

Pharmaceutics 2022, 14(11), 2279; https://doi.org/10.3390/pharmaceutics14112279 - 24 Oct 2022

Cited by 20 | Viewed by 2259

Abstract

Conventional photothermal therapy (PTT) irradiates the tumor tissues by elevating the temperature above 48 °C to exert thermal ablation, killing tumor cells. However, thermal ablation during PTT harmfully damages the surrounding normal tissues, post-treatment inflammatory responses, rapid metastasis due to the short-term mass [...] Read more.

Conventional photothermal therapy (PTT) irradiates the tumor tissues by elevating the temperature above 48 °C to exert thermal ablation, killing tumor cells. However, thermal ablation during PTT harmfully damages the surrounding normal tissues, post-treatment inflammatory responses, rapid metastasis due to the short-term mass release of tumor-cellular contents, or other side effects. To circumvent this limitation, mild-temperature photothermal therapy (MTPTT) was introduced to replace PTT as it exerts its activity at a therapeutic temperature of 42–45 °C. However, the significantly low therapeutic effect comes due to the thermoresistance of cancer cells as MTPTT figures out some of the side-effects issues. Herein, our current review suggested the mechanism and various strategies for improving the efficacy of MTPTT. Especially, heat shock proteins (HSPs) are molecular chaperones overexpressed in tumor cells and implicated in several cellular heat shock responses. Therefore, we introduced some methods to inhibit activity, reduce expression levels, and hinder the function of HSPs during MTPTT treatment. Moreover, other strategies also were emphasized, including nucleus damage, energy inhibition, and autophagy mediation. In addition, some therapies, like radiotherapy, chemotherapy, photodynamic therapy, and immunotherapy, exhibited a significant synergistic effect to assist MTPTT. Our current review provides a basis for further studies and a new approach for the clinical application of MTPTT. Full article

(This article belongs to the Special Issue Advances in Phototherapy and Sonodynamic Therapy)

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