Research

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18 pages, 3848 KiB

Open AccessArticle

Interaction of Near-Infrared (NIR)-Light Responsive Probes with Lipid Membranes: A Combined Simulation and Experimental Study

by Hugo A. L. Filipe, André F. Moreira, Sónia P. Miguel, Maximiano P. Ribeiro and Paula Coutinho

Pharmaceutics 2023, 15(7), 1853; https://doi.org/10.3390/pharmaceutics15071853 - 30 Jun 2023

Viewed by 1226

Abstract

Cancer is considered a major societal challenge for the next decade worldwide. Developing strategies for simultaneous diagnosis and treatment has been considered a promising tool for fighting cancer. For this, the development of nanomaterials incorporating prototypic near-infrared (NIR)-light responsive probes, such as heptamethine [...] Read more.

Cancer is considered a major societal challenge for the next decade worldwide. Developing strategies for simultaneous diagnosis and treatment has been considered a promising tool for fighting cancer. For this, the development of nanomaterials incorporating prototypic near-infrared (NIR)-light responsive probes, such as heptamethine cyanines, has been showing very promising results. The heptamethine cyanine-incorporating nanomaterials can be used for a tumor’s visualization and, upon interaction with NIR light, can also produce a photothermal/photodynamic effect with a high spatio-temporal resolution and minimal side effects, leading to an improved therapeutic outcome. In this work, we studied the interaction of 12 NIR-light responsive probes with lipid membrane models by molecular dynamics simulations. We performed a detailed characterization of the location, orientation, and local perturbation effects of these molecules on the lipid bilayer. Based on this information, the probes were divided into two groups, predicting a lower and higher perturbation of the lipid bilayer. From each group, one molecule was selected for testing in a membrane leakage assay. The experimental data validate the hypothesis that molecules with charged substituents, which function as two polar anchors for the aqueous phase while spanning the membrane thickness, are more likely to disturb the membrane by the formation of defects and pores, increasing the membrane leakage. The obtained results are expected to contribute to the selection of the most suitable molecules for the desired application or eventually guiding the design of probe modifications for achieving an optimal interaction with tumor cell membranes. Full article

(This article belongs to the Special Issue Recent Advances in Anticancer Photodynamic Therapy)

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27 pages, 5571 KiB

Open AccessArticle

Development of Berberine-Loaded Nanoparticles for Astrocytoma Cells Administration and Photodynamic Therapy Stimulation

by Sergio Comincini, Federico Manai, Milena Sorrenti, Sara Perteghella, Camilla D’Amato, Dalila Miele, Laura Catenacci and Maria Cristina Bonferoni

Pharmaceutics 2023, 15(4), 1078; https://doi.org/10.3390/pharmaceutics15041078 - 27 Mar 2023

Cited by 6 | Viewed by 1891

Abstract

Berberine (BBR) is known for its antitumor activity and photosensitizer properties in anti-cancer photodynamic therapy (PDT), and it has previously been favorably assayed against glioblastoma multiforme (GBM)-derived cells. In this work, two BBR hydrophobic salts, dodecyl sulfate (S) and laurate (L), have been [...] Read more.

Berberine (BBR) is known for its antitumor activity and photosensitizer properties in anti-cancer photodynamic therapy (PDT), and it has previously been favorably assayed against glioblastoma multiforme (GBM)-derived cells. In this work, two BBR hydrophobic salts, dodecyl sulfate (S) and laurate (L), have been encapsulated in PLGA-based nanoparticles (NPs), chitosan-coated by the addition of chitosan oleate in the preparation. NPs were also further functionalized with folic acid. All the BBR-loaded NPs were efficiently internalized into T98G GBM established cells, and internalization increased in the presence of folic acid. However, the highest mitochondrial co-localization percentages were obtained with BBR-S NPs without folic acid content. In the T98G cells, BBR-S NPs appeared to be the most efficient in inducing cytotoxicity events and were therefore selected to assess the effect of photodynamic stimulation (PDT). As a result, PDT potentiated the viability reduction for the BBR-S NPs at all the studied concentrations, and a roughly 50% reduction of viability was obtained. No significant cytotoxic effect on normal rat primary astrocytes was observed. In GBM cells, a significant increase in early and late apoptotic events was scored by BBR NPs, with a further increase following the PDT scheme. Furthermore, a significantly increased depolarization of mitochondria was highlighted following BBR-S NPs’ internalization and mostly after PDT stimulation, compared to untreated and PDT-only treated cells. In conclusion, these results highlighted the efficacy of the BBR-NPs-based strategy coupled with photoactivation approaches to induce favorable cytotoxic effects in GBM cells. Full article

(This article belongs to the Special Issue Recent Advances in Anticancer Photodynamic Therapy)

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12 pages, 2896 KiB

Open AccessArticle

Real-Time Monitoring of Colorectal Cancer Location and Lymph Node Metastasis and Photodynamic Therapy Using Fucoidan-Based Therapeutic Nanogel and Near-Infrared Fluorescence Diagnostic–Therapy System

by Yoo-kyoung Shin, You-rim Park, Hyeri Lee, Yongdoo Choi and Joo Beom Eom

Pharmaceutics 2023, 15(3), 930; https://doi.org/10.3390/pharmaceutics15030930 - 13 Mar 2023

Cited by 4 | Viewed by 1440

Abstract

We report real-time monitoring of colorectal cancer, lymph node metastasis of colorectal cancer cells, and tumor growth inhibition through photodynamic therapy (PDT) using a near-infrared fluorescence diagnostic–therapy system with a light source for PDT and a fucoidan-based theranostic nanogel (CFN-gel) with good accumulation [...] Read more.

We report real-time monitoring of colorectal cancer, lymph node metastasis of colorectal cancer cells, and tumor growth inhibition through photodynamic therapy (PDT) using a near-infrared fluorescence diagnostic–therapy system with a light source for PDT and a fucoidan-based theranostic nanogel (CFN-gel) with good accumulation efficiency in cancer cells. To confirm the effect of the fabricated system and developed CFN-gel, in vitro and in vivo experiments were performed. Chlorin e6 (Ce6) and 5-aminolevulinic acid (5-ALA) were used for comparison. We confirmed that CFN-gel has a high accumulation efficiency in cancer cells and high fluorescence signals in near-infrared light for a long period, and only CFN-gel delayed the growth rate of cancer in terms of its size in PDT. In addition, using the near-infrared fluorescence diagnostic–therapy system and CFN-gel prepared for these experiments, the lymph node metastasis of cancer cells was imaged in real time, and the metastasis was confirmed through H&E staining. The possibility of image-guided surgery and identification of lymph node metastasis in colorectal cancer can be confirmed through CFN-gel and a near-infrared fluorescence diagnostic–therapy system that includes various light sources. Full article

(This article belongs to the Special Issue Recent Advances in Anticancer Photodynamic Therapy)

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17 pages, 3786 KiB

Open AccessArticle

Identification of Blood Transport Proteins to Carry Temoporfin: A Domino Approach from Virtual Screening to Synthesis and In Vitro PDT Testing

by Alessia Marconi, Giulia Giugliano, Matteo Di Giosia, Tainah Dorina Marforio, Michele Trivini, Eleonora Turrini, Carmela Fimognari, Francesco Zerbetto, Edoardo Jun Mattioli and Matteo Calvaresi

Pharmaceutics 2023, 15(3), 919; https://doi.org/10.3390/pharmaceutics15030919 - 11 Mar 2023

Cited by 3 | Viewed by 1301

Abstract

Temoporfin (mTHPC) is one of the most promising photosensitizers used in photodynamic therapy (PDT). Despite its clinical use, the lipophilic character of mTHPC still hampers the full exploitation of its potential. Low solubility in water, high tendency to aggregate, and low biocompatibility are [...] Read more.

Temoporfin (mTHPC) is one of the most promising photosensitizers used in photodynamic therapy (PDT). Despite its clinical use, the lipophilic character of mTHPC still hampers the full exploitation of its potential. Low solubility in water, high tendency to aggregate, and low biocompatibility are the main limitations because they cause poor stability in physiological environments, dark toxicity, and ultimately reduce the generation of reactive oxygen species (ROS). Applying a reverse docking approach, here, we identified a number of blood transport proteins able to bind and disperse monomolecularly mTHPC, namely apohemoglobin, apomyoglobin, hemopexin, and afamin. We validated the computational results synthesizing the mTHPC-apomyoglobin complex (mTHPC@apoMb) and demonstrated that the protein monodisperses mTHPC in a physiological environment. The mTHPC@apoMb complex preserves the imaging properties of the molecule and improves its ability to produce ROS via both type I and type II mechanisms. The effectiveness of photodynamic treatment using the mTHPC@apoMb complex was then demonstrated in vitro. Blood transport proteins can be used as molecular “Trojan horses” in cancer cells by conferring mTHPC (i) water solubility, (ii) monodispersity, and (iii) biocompatibility, ultimately bypassing the current limitations of mTHPC. Full article

(This article belongs to the Special Issue Recent Advances in Anticancer Photodynamic Therapy)

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15 pages, 1311 KiB

Open AccessArticle

Monocationic Chlorin as a Promising Photosensitizer for Antitumor and Antimicrobial Photodynamic Therapy

by Andrey V. Kustov, Dmitry B. Berezin, Vladimir P. Zorin, Philipp K. Morshnev, Natal’ya V. Kukushkina, Mikhail A. Krestyaninov, Tatyana V. Kustova, Alexander I. Strelnikov, Elena V. Lyalyakina, Tatyana E. Zorina, Olga B. Abramova and Ekaterina A. Kozlovtseva

Pharmaceutics 2023, 15(1), 61; https://doi.org/10.3390/pharmaceutics15010061 - 25 Dec 2022

Cited by 9 | Viewed by 2288

Abstract

Cancer is one of the leading causes of death worldwide. Despite substantial progress in the understanding of tumor biology, and the appearance of new generations of targeted drugs and treatment techniques, the success achieved in this battle, with some notable exceptions, is still [...] Read more.

Cancer is one of the leading causes of death worldwide. Despite substantial progress in the understanding of tumor biology, and the appearance of new generations of targeted drugs and treatment techniques, the success achieved in this battle, with some notable exceptions, is still only moderate. Photodynamic therapy (PDT) is a successful but still underestimated therapeutic modality for treating many superficial cancers. In this paper, we focus on the extensive investigation of the monocationic chlorin photosensitizer (PS), considered here as a new photosensitizing agent for both antitumor and antimicrobial PDT. This monocationic chlorin PS (McChl) obtained from methylpheophorbide a (MPh) via a two-step procedure is well soluble in water in the physiological temperature range and forms stable complexes with passive carriers. McChl generates singlet oxygen with a good quantum yield in a lipid-like environment and binds mainly to low- and high-density lipoproteins in a vascular system. A comparison of the photodynamic activity of this agent with the activity of the well-established photosensitizer chlorin e₆ (Chl e₆) clearly indicates that McChl provides a much more efficient photoinactivation of malignant and microbial cells. The pilot PDT treatment of M1 sarcoma-bearing rats with this PS demonstrates its good potential for further preclinical investigations. Full article

(This article belongs to the Special Issue Recent Advances in Anticancer Photodynamic Therapy)

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Review

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17 pages, 2442 KiB

Open AccessReview

An Update on Recent Advances of Photodynamic Therapy for Primary Cutaneous Lymphomas

by Wei-Ting Liu, Han-Tang Wang, Yi-Hsuan Yeh and Tak-Wah Wong

Pharmaceutics 2023, 15(5), 1328; https://doi.org/10.3390/pharmaceutics15051328 - 24 Apr 2023

Cited by 5 | Viewed by 1780

Abstract

Primary cutaneous lymphomas are rare non-Hodgkin lymphomas consisting of heterogeneous disease entities. Photodynamic therapy (PDT) utilizing photosensitizers irradiated with a specific wavelength of light in the presence of oxygen exerts promising anti-tumor effects on non-melanoma skin cancer, yet its application in primary cutaneous [...] Read more.

Primary cutaneous lymphomas are rare non-Hodgkin lymphomas consisting of heterogeneous disease entities. Photodynamic therapy (PDT) utilizing photosensitizers irradiated with a specific wavelength of light in the presence of oxygen exerts promising anti-tumor effects on non-melanoma skin cancer, yet its application in primary cutaneous lymphomas remains less recognized. Despite many in vitro data showing PDT could effectively kill lymphoma cells, clinical evidence of PDT against primary cutaneous lymphomas is limited. Recently, a phase 3 “FLASH” randomized clinical trial demonstrated the efficacy of topical hypericin PDT for early-stage cutaneous T-cell lymphoma. An update on recent advances of photodynamic therapy in primary cutaneous lymphomas is provided. Full article

(This article belongs to the Special Issue Recent Advances in Anticancer Photodynamic Therapy)

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15 pages, 10314 KiB

Open AccessReview

Recent Advances of Photoactive Near-Infrared Carbon Dots in Cancer Photodynamic Therapy

by Jinxing Song, Xiaobo Gao, Mei Yang, Weiju Hao and Ding-Kun Ji

Pharmaceutics 2023, 15(3), 760; https://doi.org/10.3390/pharmaceutics15030760 - 24 Feb 2023

Cited by 4 | Viewed by 1697

Abstract

Photodynamic therapy (PDT) is a treatment that employs exogenously produced reactive oxygen species (ROS) to kill cancer cells. ROS are generated from the interaction of excited-state photosensitizers (PSs) or photosensitizing agents with molecular oxygen. Novel PSs with high ROS generation efficiency is essential [...] Read more.

Photodynamic therapy (PDT) is a treatment that employs exogenously produced reactive oxygen species (ROS) to kill cancer cells. ROS are generated from the interaction of excited-state photosensitizers (PSs) or photosensitizing agents with molecular oxygen. Novel PSs with high ROS generation efficiency is essential and highly required for cancer photodynamic therapy. Carbon dots (CDs), the rising star of carbon-based nanomaterial family, have shown great potential in cancer PDT benefiting from their excellent photoactivity, luminescence properties, low price, and biocompatibility. In recent years, photoactive near-infrared CDs (PNCDs) have attracted increasing interest in this field due to their deep therapeutic tissue penetration, superior imaging performance, excellent photoactivity, and photostability. In this review, we review recent progress in the designs, fabrication, and applications of PNCDs in cancer PDT. We also provide insights of future directions in accelerating the clinical progress of PNCDs. Full article

(This article belongs to the Special Issue Recent Advances in Anticancer Photodynamic Therapy)

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27 pages, 7488 KiB

Open AccessReview

Recent Progress of Gold-Based Nanostructures towards Future Emblem of Photo-Triggered Cancer Theranostics: A Special Focus on Combinatorial Phototherapies

by Rajkumar Sekar, Nagaraj Basavegowda, Jesse Joel Thathapudi, Medidi Raja Sekhar, Parinita Joshi, Prathap Somu and Kwang-Hyun Baek

Pharmaceutics 2023, 15(2), 433; https://doi.org/10.3390/pharmaceutics15020433 - 28 Jan 2023

Cited by 6 | Viewed by 1678

Abstract

Cancer is one of the most dangerous health problems in the millennium and it is the third foremost human cause of death in the universe. Traditional cancer treatments face several disadvantages and cannot often afford adequate outcomes. It has been exhibited that the [...] Read more.

Cancer is one of the most dangerous health problems in the millennium and it is the third foremost human cause of death in the universe. Traditional cancer treatments face several disadvantages and cannot often afford adequate outcomes. It has been exhibited that the outcome of several therapies can be improved when associated with nanostructures. In addition, a modern tendency is being developed in cancer therapy to convert single-modal into multi-modal therapies with the help of existing various nanostructures. Among them, gold is the most successful nanostructure for biomedical applications due to its flexibility in preparation, stabilization, surface modifications, less cytotoxicity, and ease of bio-detection. In the past few decades, gold-based nanomaterials rule cancer treatment applications, currently, gold nanostructures were the leading nanomaterials for synergetic cancer therapies. In this review article, the synthesis, stabilization, and optical properties of gold nanostructures have been discussed. Then, the surface modifications and targeting mechanisms of gold nanomaterials will be described. Recent signs of progress in the application of gold nanomaterials for synergetic cancer therapies such as photodynamic and photo-thermal therapies in combination with other common interventions such as radiotherapy, chemotherapy, and will be reviewed. Also, a summary of the pharmacokinetics of gold nanostructures will be delivered. Finally, the challenges and outlooks of the gold nanostructures in the clinics for applications in cancer treatments are debated. Full article

(This article belongs to the Special Issue Recent Advances in Anticancer Photodynamic Therapy)

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41 pages, 2917 KiB

Open AccessReview

Current Challenges and Opportunities of Photodynamic Therapy against Cancer

by Ruben V. Huis in ‘t Veld, Jeroen Heuts, Sen Ma, Luis J. Cruz, Ferry A. Ossendorp and Martine J. Jager

Pharmaceutics 2023, 15(2), 330; https://doi.org/10.3390/pharmaceutics15020330 - 18 Jan 2023

Cited by 37 | Viewed by 3455

Abstract

BACKGROUND: Photodynamic therapy (PDT) is an established, minimally invasive treatment for specific types of cancer. During PDT, reactive oxygen species (ROS) are generated that ultimately induce cell death and disruption of the tumor area. Moreover, PDT can result in damage to the tumor [...] Read more.

BACKGROUND: Photodynamic therapy (PDT) is an established, minimally invasive treatment for specific types of cancer. During PDT, reactive oxygen species (ROS) are generated that ultimately induce cell death and disruption of the tumor area. Moreover, PDT can result in damage to the tumor vasculature and induce the release and/or exposure of damage-associated molecular patterns (DAMPs) that may initiate an antitumor immune response. However, there are currently several challenges of PDT that limit its widespread application for certain indications in the clinic. METHODS: A literature study was conducted to comprehensively discuss these challenges and to identify opportunities for improvement. RESULTS: The most notable challenges of PDT and opportunities to improve them have been identified and discussed. CONCLUSIONS: The recent efforts to improve the current challenges of PDT are promising, most notably those that focus on enhancing immune responses initiated by the treatment. The application of these improvements has the potential to enhance the antitumor efficacy of PDT, thereby broadening its potential application in the clinic. Full article

(This article belongs to the Special Issue Recent Advances in Anticancer Photodynamic Therapy)

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