Editorial

4 pages, 185 KiB

Open AccessEditorial

by Francesca Moret and Greta Varchi

Pharmaceutics 2023, 15(7), 1784; https://doi.org/10.3390/pharmaceutics15071784 - 21 Jun 2023

Cited by 1 | Viewed by 1049

Photodynamic therapy (PDT) has gained prominence as a non-invasive and selective treatment option for solid tumors and non-oncological diseases [...] Full article

(This article belongs to the Special Issue Drug Delivery in Photodynamic Therapy (PDT))

Research

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13 pages, 2336 KiB

Open AccessCommunication

Enabling In Vivo Optical Imaging of an Osmium Photosensitizer by Micellar Formulation

by Drashti Shah, Menitte Eroy, John Fakhry, Azophi Moffat, Kevin Fritz, Houston D. Cole, Colin G. Cameron, Sherri A. McFarland and Girgis Obaid

Pharmaceutics 2022, 14(11), 2426; https://doi.org/10.3390/pharmaceutics14112426 - 10 Nov 2022

Cited by 2 | Viewed by 2133

Abstract

Osmium (Os)-based photosensitizers (PSs) exhibit unique broad, red-shifted absorption, favoring PDT activity at greater tissue depths. We recently reported on a potent Os(II) PS, rac-[Os(phen)₂(IP-4T)](Cl)₂ (ML18J03) with submicromolar hypoxia activity. ML18J03 exhibits a low luminescence quantum yield of 9.8 [...] Read more.

Osmium (Os)-based photosensitizers (PSs) exhibit unique broad, red-shifted absorption, favoring PDT activity at greater tissue depths. We recently reported on a potent Os(II) PS, rac-[Os(phen)₂(IP-4T)](Cl)₂ (ML18J03) with submicromolar hypoxia activity. ML18J03 exhibits a low luminescence quantum yield of 9.8 × 10⁻⁵ in PBS, which limits its capacity for in vivo luminescence imaging. We recently showed that formulating ML18J03 into 10.2 nm DSPE-mPEG₂₀₀₀ micelles (Mic-ML18J03) increases its luminescence quantum yield by two orders of magnitude. Here, we demonstrate that Mic-ML18J03 exhibits 47-fold improved accumulative luminescence signals in orthotopic AT-84 head and neck tumors. We show, for the first time, that micellar formulation provides up to 11.7-fold tumor selectivity for ML18J03. Furthermore, Mic-ML18J03 does not experience the concentration-dependent quenching observed with unformulated ML18J03 in PBS, and formulation reduces spectral shifting of the emission maxima during PDT (variance = 6.5 and 27.3, respectively). The Mic-ML18J03 formulation also increases the production of reactive molecular species 2–3-fold. These findings demonstrate that micellar formulation is a versatile and effective approach to enable in vivo luminescence imaging options for an otherwise quenched, yet promising, PS. Full article

(This article belongs to the Special Issue Drug Delivery in Photodynamic Therapy (PDT))

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20 pages, 9918 KiB

Open AccessArticle

Two Beats One: Osteosarcoma Therapy with Light-Activated and Chemo-Releasing Keratin Nanoformulation in a Preclinical Mouse Model

by Elisa Martella, Barbara Dozza, Claudia Ferroni, Clement Osuru Obeyok, Andrea Guerrini, Daniele Tedesco, Ilse Manet, Giovanna Sotgiu, Marta Columbaro, Marco Ballestri, Lucia Martini, Milena Fini, Enrico Lucarelli, Greta Varchi and Serena Duchi

Pharmaceutics 2022, 14(3), 677; https://doi.org/10.3390/pharmaceutics14030677 - 19 Mar 2022

Cited by 8 | Viewed by 2837

Abstract

Osteosarcoma treatment is moving towards more effective combination therapies. Nevertheless, these approaches present distinctive challenges that can complicate the clinical translation, such as increased toxicity and multi-drug resistance. Drug co-encapsulation within a nanoparticle formulation can overcome these challenges and improve the therapeutic index. [...] Read more.

Osteosarcoma treatment is moving towards more effective combination therapies. Nevertheless, these approaches present distinctive challenges that can complicate the clinical translation, such as increased toxicity and multi-drug resistance. Drug co-encapsulation within a nanoparticle formulation can overcome these challenges and improve the therapeutic index. We previously synthetized keratin nanoparticles functionalized with Chlorin-e6 (Ce6) and paclitaxel (PTX) to combine photo (PDT) and chemotherapy (PTX) regimens, and the inhibition of osteosarcoma cells growth in vitro was demonstrated. In the current study, we generated an orthotopic osteosarcoma murine model for the preclinical evaluation of our combination therapy. To achieve maximum reproducibility, we systematically established key parameters, such as the number of cells to generate the tumor, the nanoparticles dose, the design of the light-delivery device, the treatment schedule, and the irradiation settings. A 60% engrafting rate was obtained using 10 million OS cells inoculated intratibial, with the tumor model recapitulating the histological hallmarks of the human counterpart. By scheduling the treatment as two cycles of injections, a 32% tumor reduction was obtained with PTX mono-therapy and a 78% reduction with the combined PTX-PDT therapy. Our findings provide the in vivo proof of concept for the subsequent clinical development of a combination therapy to fight osteosarcoma. Full article

(This article belongs to the Special Issue Drug Delivery in Photodynamic Therapy (PDT))

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21 pages, 6671 KiB

Open AccessArticle

Photosensitive EGFR-Targeted Nanocarriers for Combined Photodynamic and Local Chemotherapy

by Elena de las Heras, M. Lluïsa Sagristá, Montserrat Agut and Santi Nonell

Pharmaceutics 2022, 14(2), 405; https://doi.org/10.3390/pharmaceutics14020405 - 13 Feb 2022

Cited by 7 | Viewed by 1766

Abstract

The major limitation of any cancer therapy lies in the difficulty of precisely controlling the localization of the drug in the tumor cells. To improve this drawback, our study explores the use of actively-targeted chemo-photo-nanocarriers that recognize and bind to epidermal growth factor [...] Read more.

The major limitation of any cancer therapy lies in the difficulty of precisely controlling the localization of the drug in the tumor cells. To improve this drawback, our study explores the use of actively-targeted chemo-photo-nanocarriers that recognize and bind to epidermal growth factor receptor-overexpressing cells and promote the local on-demand release of the chemotherapeutic agent doxorubicin triggered by light. Our results show that the attachment of high concentrations of doxorubicin to cetuximab-IRDye700DX-mesoporous silica nanoparticles yields efficient and selective photokilling of EGFR-expressing cells mainly through singlet oxygen-induced release of the doxorubicin from the nanocarrier and without any dark toxicity. Therefore, this novel triply functionalized nanosystem is an effective and safe nanodevice for light-triggered on-demand doxorubicin release. Full article

(This article belongs to the Special Issue Drug Delivery in Photodynamic Therapy (PDT))

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13 pages, 3758 KiB

Open AccessArticle

Therapeutic Options for Recurrent Glioblastoma—Efficacy of Talaporfin Sodium Mediated Photodynamic Therapy

by Tatsuya Kobayashi, Masayuki Nitta, Kazuhide Shimizu, Taiichi Saito, Shunsuke Tsuzuki, Atsushi Fukui, Shunichi Koriyama, Atsushi Kuwano, Takashi Komori, Kenta Masui, Taketoshi Maehara, Takakazu Kawamata and Yoshihiro Muragaki

Pharmaceutics 2022, 14(2), 353; https://doi.org/10.3390/pharmaceutics14020353 - 02 Feb 2022

Cited by 11 | Viewed by 1977

Abstract

Recurrent glioblastoma (GBM) remains one of the most challenging clinical issues, with no standard treatment and effective treatment options. To evaluate the efficacy of talaporfin sodium (TS) mediated photodynamic therapy (PDT) as a new treatment for this condition, we retrospectively analyzed 70 patients [...] Read more.

Recurrent glioblastoma (GBM) remains one of the most challenging clinical issues, with no standard treatment and effective treatment options. To evaluate the efficacy of talaporfin sodium (TS) mediated photodynamic therapy (PDT) as a new treatment for this condition, we retrospectively analyzed 70 patients who underwent surgery with PDT (PDT group) for recurrent GBM and 38 patients who underwent surgery alone (control group). The median progression-free survival (PFS) in the PDT and control groups after second surgery was 5.7 and 2.2 months, respectively (p = 0.0043). The median overall survival (OS) after the second surgery was 16.0 and 12.8 months, respectively (p = 0.031). Both univariate and multivariate analyses indicated that surgery with PDT and a preoperative Karnofsky Performance Scale were significant independent prognostic factors for PFS and OS. In the PDT group, there was no significant difference regarding PFS and OS between patients whose previous pathology before recurrence was already GBM and those who had malignant transformation to GBM from lower grade glioma. There was also no significant difference in TS accumulation in the tumor between these two groups. According to these results, additional PDT treatment for recurrent GBM could have potential survival benefits and its efficacy is independent of the pre-recurrence pathology. Full article

(This article belongs to the Special Issue Drug Delivery in Photodynamic Therapy (PDT))

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24 pages, 53198 KiB

Open AccessArticle

Photochemical Internalization of Etoposide Using Dendrimer Nanospheres Loaded with Etoposide and Protoporphyrin IX on a Glioblastoma Cell Line

by Martin Hsiu-Chu Lin, Li-Ching Chang, Chiu-Yen Chung, Wei-Chao Huang, Ming-Hsueh Lee, Kuo-Tai Chen, Ping-Shan Lai and Jen-Tsung Yang

Pharmaceutics 2021, 13(11), 1877; https://doi.org/10.3390/pharmaceutics13111877 - 05 Nov 2021

Cited by 5 | Viewed by 2001

Abstract

Glioblastoma multiforme (GBM) is the most common malignant primary neoplasm of the adult central nervous system originating from glial cells. The prognosis of those affected by GBM has remained poor despite advances in surgery, chemotherapy, and radiotherapy. Photochemical internalization (PCI) is a release [...] Read more.

Glioblastoma multiforme (GBM) is the most common malignant primary neoplasm of the adult central nervous system originating from glial cells. The prognosis of those affected by GBM has remained poor despite advances in surgery, chemotherapy, and radiotherapy. Photochemical internalization (PCI) is a release mechanism of endocytosed therapeutics into the cytoplasm, which relies on the membrane disruptive effect of light-activated photosensitizers. In this study, phototherapy by PCI was performed on a human GBM cell-line using the topoisomerase II inhibitor etoposide (Etop) and the photosensitizer protoporphyrin IX (PpIX) loaded in nanospheres (Ns) made from generation-5 polyamidoamine dendrimers (PAMAM(G5)). The resultant formulation, Etop/PpIX-PAMAM(G5) Ns, measured 217.4 ± 2.9 nm in diameter and 40.5 ± 1.3 mV in charge. Confocal microscopy demonstrated PpIX fluorescence within the endo-lysosomal compartment, and an almost twofold increase in cellular uptake compared to free PpIX by flow cytometry. Phototherapy with 3 min and 5 min light illumination resulted in a greater extent of synergism than with co-administered Etop and PpIX; notably, antagonism was observed without light illumination. Mechanistically, significant increases in oxidative stress and apoptosis were observed with Etop/PpIX-PAMAM(G5) Ns upon 5 min of light illumination in comparison to treatment with either of the agents alone. In conclusion, simultaneous delivery and endo-lysosomal co-localization of Etop and PpIX by PAMAM(G5) Ns leads to a synergistic effect by phototherapy; in addition, the finding of antagonism without light illumination can be advantageous in lowering the dark toxicity and improving photo-selectivity. Full article

(This article belongs to the Special Issue Drug Delivery in Photodynamic Therapy (PDT))

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22 pages, 7940 KiB

Open AccessArticle

Graphene Oxide and Graphene Quantum Dots as Delivery Systems of Cationic Porphyrins: Photo-Antiproliferative Activity Evaluation towards T24 Human Bladder Cancer Cells

by Luca Menilli, Ana R. Monteiro, Silvia Lazzarotto, Filipe M. P. Morais, Ana T. P. C. Gomes, Nuno M. M. Moura, Sara Fateixa, Maria A. F. Faustino, Maria G. P. M. S. Neves, Tito Trindade and Giorgia Miolo

Pharmaceutics 2021, 13(9), 1512; https://doi.org/10.3390/pharmaceutics13091512 - 18 Sep 2021

Cited by 19 | Viewed by 4362

Abstract

The development of new photodynamic therapy (PDT) agents designed for bladder cancer (BC) treatments is of utmost importance to prevent its recurrence and progression towards more invasive forms. Here, three different porphyrinic photosensitizers (PS) (TMPyP, Zn-TMPyP, and P1-C₅) were non-covalently loaded [...] Read more.

The development of new photodynamic therapy (PDT) agents designed for bladder cancer (BC) treatments is of utmost importance to prevent its recurrence and progression towards more invasive forms. Here, three different porphyrinic photosensitizers (PS) (TMPyP, Zn-TMPyP, and P1-C₅) were non-covalently loaded onto graphene oxide (GO) or graphene quantum dots (GQDs) in a one-step process. The cytotoxic effects of the free PS and of the corresponding hybrids were compared upon blue (BL) and red-light (RL) exposure on T24 human BC cells. In addition, intracellular reactive oxygen species (ROS) and singlet oxygen generation were measured. TMPyP and Zn-TMPyP showed higher efficiency under BL (IC₅₀: 0.42 and 0.22 μm, respectively), while P1-C₅ was more active under RL (IC₅₀: 0.14 μm). In general, these PS could induce apoptotic cell death through lysosomes damage. The in vitro photosensitizing activity of the PS was not compromised after their immobilization onto graphene-based nanomaterials, with Zn-TMPyP@GQDs being the most promising hybrid system under RL (IC₅₀: 0.37 μg/mL). Overall, our data confirm that GO and GQDs may represent valid platforms for PS delivery, without altering their performance for PDT on BC cells. Full article

(This article belongs to the Special Issue Drug Delivery in Photodynamic Therapy (PDT))

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22 pages, 3424 KiB

Open AccessArticle

Combining Photodynamic Therapy with Immunostimulatory Nanoparticles Elicits Effective Anti-Tumor Immune Responses in Preclinical Murine Models

by Ruben Victor Huis in ‘t Veld, Candido G. Da Silva, Martine J. Jager, Luis J. Cruz and Ferry Ossendorp

Pharmaceutics 2021, 13(9), 1470; https://doi.org/10.3390/pharmaceutics13091470 - 14 Sep 2021

Cited by 13 | Viewed by 3187

Abstract

Photodynamic therapy (PDT) has shown encouraging but limited clinical efficacy when used as a standalone treatment against solid tumors. Conversely, a limitation for immunotherapeutic efficacy is related to the immunosuppressive state observed in large, advanced tumors. In the present study, we employ a [...] Read more.

Photodynamic therapy (PDT) has shown encouraging but limited clinical efficacy when used as a standalone treatment against solid tumors. Conversely, a limitation for immunotherapeutic efficacy is related to the immunosuppressive state observed in large, advanced tumors. In the present study, we employ a strategy, in which we use a combination of PDT and immunostimulatory nanoparticles (NPs), consisting of poly(lactic-co-glycolic) acid (PLGA)-polyethylene glycol (PEG) particles, loaded with the Toll-like receptor 3 (TLR3) agonist poly(I:C), the TLR7/8 agonist R848, the lymphocyte-attracting chemokine, and macrophage inflammatory protein 3α (MIP3α). The combination provoked strong anti-tumor responses, including an abscopal effects, in three clinically relevant murine models of cancer: MC38 (colorectal), CT26 (colorectal), and TC-1 (human papillomavirus 16-induced). We show that the local and distal anti-tumor effects depended on the presence of CD8⁺ T cells. The combination elicited tumor-specific oncoviral- or neoepitope-directed CD8⁺ T cells immune responses against the respective tumors, providing evidence that PDT can be used as an in situ vaccination strategy against cancer (neo)epitopes. Finally, we show that the treatment alters the tumor microenvironment in tumor-bearing mice, from cold (immunosuppressed) to hot (pro-inflammatory), based on greater neutrophil infiltration and higher levels of inflammatory myeloid and CD8⁺ T cells, compared to untreated mice. Together, our results provide a rationale for combining PDT with immunostimulatory NPs for the treatment of solid tumors. Full article

(This article belongs to the Special Issue Drug Delivery in Photodynamic Therapy (PDT))

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17 pages, 2640 KiB

Open AccessArticle

Pheophorbide A and Paclitaxel Bioresponsive Nanoparticles as Double-Punch Platform for Cancer Therapy

by Francesca Moret, Luca Menilli, Manuele Battan, Daniele Tedesco, Marta Columbaro, Andrea Guerrini, Greta Avancini, Claudia Ferroni and Greta Varchi

Pharmaceutics 2021, 13(8), 1130; https://doi.org/10.3390/pharmaceutics13081130 - 23 Jul 2021

Cited by 10 | Viewed by 3127

Abstract

Cancer therapy is still a challenging issue. To address this, the combination of anticancer drugs with other therapeutic modalities, such as light-triggered therapies, has emerged as a promising approach, primarily when both active ingredients are provided within a single nanosystem. Herein, we describe [...] Read more.

Cancer therapy is still a challenging issue. To address this, the combination of anticancer drugs with other therapeutic modalities, such as light-triggered therapies, has emerged as a promising approach, primarily when both active ingredients are provided within a single nanosystem. Herein, we describe the unprecedented preparation of tumor microenvironment (TME) responsive nanoparticles exclusively composed of a paclitaxel (PTX) prodrug and the photosensitizer pheophorbide A (PheoA), e.g., PheoA≅PTX₂S. This system aimed to achieve both the TME-triggered and controlled release of PTX and the synergistic/additive effect by PheoA-mediated photodynamic therapy. PheoA≅PTX₂S were produced in a simple one-pot process, exhibiting excellent reproducibility, stability, and the ability to load up to 100% PTX and 40% of PheoA. Exposure of PheoA≅PTX₂S nanoparticles to TME-mimicked environment provided fast disassembly compared to normal conditions, leading to PTX and PheoA release and consequently elevated cytotoxicity. Our data indicate that PheoA incorporation into nanoparticles prevents its aggregation, thus providing a greater extent of ROS and singlet oxygen production. Importantly, in SK-OV-3 cells, PheoA≅PTX₂S allowed a 30-fold PTX dose reduction and a 3-fold dose reduction of PheoA. Our data confirm that prodrug-based nanocarriers represent valuable and sustainable drug delivery systems, possibly reducing toxicity and expediting preclinical and clinical translation. Full article

(This article belongs to the Special Issue Drug Delivery in Photodynamic Therapy (PDT))

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Review

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44 pages, 3529 KiB

Open AccessEditor’s ChoiceReview

EGFR-Targeted Photodynamic Therapy

by Luca Ulfo, Paolo Emidio Costantini, Matteo Di Giosia, Alberto Danielli and Matteo Calvaresi

Pharmaceutics 2022, 14(2), 241; https://doi.org/10.3390/pharmaceutics14020241 - 20 Jan 2022

Cited by 34 | Viewed by 4664

Abstract

The epidermal growth factor receptor (EGFR) plays a pivotal role in the proliferation and metastatization of cancer cells. Aberrancies in the expression and activation of EGFR are hallmarks of many human malignancies. As such, EGFR-targeted therapies hold significant potential for the cure of [...] Read more.

The epidermal growth factor receptor (EGFR) plays a pivotal role in the proliferation and metastatization of cancer cells. Aberrancies in the expression and activation of EGFR are hallmarks of many human malignancies. As such, EGFR-targeted therapies hold significant potential for the cure of cancers. In recent years, photodynamic therapy (PDT) has gained increased interest as a non-invasive cancer treatment. In PDT, a photosensitizer is excited by light to produce reactive oxygen species, resulting in local cytotoxicity. One of the critical aspects of PDT is to selectively transport enough photosensitizers to the tumors environment. Accordingly, an increasing number of strategies have been devised to foster EGFR-targeted PDT. Herein, we review the recent nanobiotechnological advancements that combine the promise of PDT with EGFR-targeted molecular cancer therapy. We recapitulate the chemistry of the sensitizers and their modes of action in PDT, and summarize the advantages and pitfalls of different targeting moieties, highlighting future perspectives for EGFR-targeted photodynamic treatment of cancer. Full article

(This article belongs to the Special Issue Drug Delivery in Photodynamic Therapy (PDT))

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43 pages, 4806 KiB

Open AccessReview

Combinatorial Therapeutic Approaches with Nanomaterial-Based Photodynamic Cancer Therapy

by Yang Hao, Chih Kit Chung, Zhenfeng Yu, Ruben V. Huis in ‘t Veld, Ferry A. Ossendorp, Peter ten Dijke and Luis J. Cruz

Pharmaceutics 2022, 14(1), 120; https://doi.org/10.3390/pharmaceutics14010120 - 04 Jan 2022

Cited by 30 | Viewed by 4549

Abstract

Photodynamic therapy (PDT), in which a light source is used in combination with a photosensitizer to induce local cell death, has shown great promise in therapeutically targeting primary tumors with negligible toxicity and minimal invasiveness. However, numerous studies have shown that noninvasive PDT [...] Read more.

Photodynamic therapy (PDT), in which a light source is used in combination with a photosensitizer to induce local cell death, has shown great promise in therapeutically targeting primary tumors with negligible toxicity and minimal invasiveness. However, numerous studies have shown that noninvasive PDT alone is not sufficient to completely ablate tumors in deep tissues, due to its inherent shortcomings. Therefore, depending on the characteristics and type of tumor, PDT can be combined with surgery, radiotherapy, immunomodulators, chemotherapy, and/or targeted therapy, preferably in a patient-tailored manner. Nanoparticles are attractive delivery vehicles that can overcome the shortcomings of traditional photosensitizers, as well as enable the codelivery of multiple therapeutic drugs in a spatiotemporally controlled manner. Nanotechnology-based combination strategies have provided inspiration to improve the anticancer effects of PDT. Here, we briefly introduce the mechanism of PDT and summarize the photosensitizers that have been tested preclinically for various cancer types and clinically approved for cancer treatment. Moreover, we discuss the current challenges facing the combination of PDT and multiple cancer treatment options, and we highlight the opportunities of nanoparticle-based PDT in cancer therapies. Full article

(This article belongs to the Special Issue Drug Delivery in Photodynamic Therapy (PDT))

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21 pages, 2493 KiB

Open AccessReview

Recent Advances in Photodynamic Therapy against Fungal Keratitis

by Jia-Horung Hung, Chaw-Ning Lee, Huai-Wen Hsu, I-Son Ng, Chi-Jung Wu, Chun-Keung Yu, Nan-Yao Lee, Yun Chang and Tak-Wah Wong

Pharmaceutics 2021, 13(12), 2011; https://doi.org/10.3390/pharmaceutics13122011 - 26 Nov 2021

Cited by 17 | Viewed by 3660

Abstract

Fungal keratitis is a serious clinical infection on the cornea caused by fungi and is one of the leading causes of blindness in Asian countries. The treatment options are currently limited to a few antifungal agents. With the increasing incidence of drug-resistant infections, [...] Read more.

Fungal keratitis is a serious clinical infection on the cornea caused by fungi and is one of the leading causes of blindness in Asian countries. The treatment options are currently limited to a few antifungal agents. With the increasing incidence of drug-resistant infections, many patients fail to respond to antibiotics. Riboflavin-mediated corneal crosslinking (similar to photodynamic therapy (PDT)) for corneal ectasia was approved in the US in the early 2000s. Current evidence suggests that PDT could have the potential to inhibit fungal biofilm formation and overcome drug resistance by using riboflavin and rose bengal as photosensitizers. However, only a few clinical trials have been initiated in anti-fungal keratitis PDT treatment. Moreover, the removal of the corneal epithelium and repeated application of riboflavin and rose bengal are required to improve drug penetration before and during PDT. Thus, an improvement in trans-corneal drug delivery is mandatory for a successful and efficient treatment. In this article, we review the studies published to date using PDT against fungal keratitis and aim to enhance the understanding and awareness of this research area. The potential of modifying photosensitizers using nanotechnology to improve the efficacy of PDT on fungal keratitis is also briefly reviewed. Full article

(This article belongs to the Special Issue Drug Delivery in Photodynamic Therapy (PDT))

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18 pages, 2178 KiB

Open AccessReview

Targeted Photodynamic Diagnosis and Therapy for Esophageal Cancer: Potential Role of Functionalized Nanomedicine

by Onyisi Christiana Didamson and Heidi Abrahamse

Pharmaceutics 2021, 13(11), 1943; https://doi.org/10.3390/pharmaceutics13111943 - 16 Nov 2021

Cited by 14 | Viewed by 2698

Abstract

Esophageal cancer is often diagnosed at the late stage when cancer has already spread and is characterized by a poor prognosis. Therefore, early diagnosis is vital for a better and efficient treatment outcome. Upper endoscopy with biopsy is the standard diagnostic tool for [...] Read more.

Esophageal cancer is often diagnosed at the late stage when cancer has already spread and is characterized by a poor prognosis. Therefore, early diagnosis is vital for a better and efficient treatment outcome. Upper endoscopy with biopsy is the standard diagnostic tool for esophageal cancer but is challenging to diagnose at its premalignant stage, while conventional treatments such as surgery, chemotherapy, and irradiation therapy, are challenging to eliminate the tumor. Photodynamic diagnosis (PDD) and therapy (PDT) modalities that employ photosensitizers (PSs) are emerging diagnostic and therapeutic strategies for esophageal cancer. However, some flaws associated with the classic PSs have limited their clinical applications. Functionalized nanomedicine has emerged as a potential drug delivery system to enhance PS drug biodistribution and cellular internalization. The conjugation of PSs with functionalized nanomedicine enables increased localization within esophageal cancer cells due to improved solubility and stability in blood circulation. This review highlights PS drugs used for PDD and PDT for esophageal cancer. In addition, it focuses on the various functionalized nanomedicine explored for esophageal cancer and their role in targeted PDD and PDT for diagnosis and treatment. Full article

(This article belongs to the Special Issue Drug Delivery in Photodynamic Therapy (PDT))

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21 pages, 1581 KiB

Open AccessReview

Biocompatible Nanocarriers for Enhanced Cancer Photodynamic Therapy Applications

by Sathish Sundar Dhilip Kumar and Heidi Abrahamse

Pharmaceutics 2021, 13(11), 1933; https://doi.org/10.3390/pharmaceutics13111933 - 15 Nov 2021

Cited by 13 | Viewed by 2506

Abstract

In recent years, the role of nanotechnology in drug delivery has become increasingly important, and this field of research holds many potential benefits for cancer treatment, particularly, in achieving cancer cell targeting and reducing the side effects of anticancer drugs. Biocompatible and biodegradable [...] Read more.

In recent years, the role of nanotechnology in drug delivery has become increasingly important, and this field of research holds many potential benefits for cancer treatment, particularly, in achieving cancer cell targeting and reducing the side effects of anticancer drugs. Biocompatible and biodegradable properties have been essential for using a novel material as a carrier molecule in drug delivery applications. Biocompatible nanocarriers are easy to synthesize, and their surface chemistry often enables them to load different types of photosensitizers (PS) to use targeted photodynamic therapy (PDT) for cancer treatment. This review article explores recent studies on the use of different biocompatible nanocarriers, their potential applications in PDT, including PS-loaded biocompatible nanocarriers, and the effective targeting therapy of PS-loaded biocompatible nanocarriers in PDT for cancer treatment. Furthermore, the review briefly recaps the global clinical trials of PDT and its applications in cancer treatment. Full article

(This article belongs to the Special Issue Drug Delivery in Photodynamic Therapy (PDT))

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22 pages, 4898 KiB

Open AccessReview

Biomimetic Nanotechnology: A Natural Path Forward for Tumor-Selective and Tumor-Specific NIR Activable Photonanomedicines

by Sushant Prajapati, Taylor Hinchliffe, Vinay Roy, Nimit Shah, Caroline N. Jones and Girgis Obaid

Pharmaceutics 2021, 13(6), 786; https://doi.org/10.3390/pharmaceutics13060786 - 25 May 2021

Cited by 8 | Viewed by 3710

Abstract

The emergence of biomimetic nanotechnology has seen an exponential rise over the past decade with applications in regenerative medicine, immunotherapy and drug delivery. In the context of nanomedicines activated by near infrared (NIR) photodynamic processes (photonanomedicines; PNMs), biomimetic nanotechnology is pushing the boundaries [...] Read more.

The emergence of biomimetic nanotechnology has seen an exponential rise over the past decade with applications in regenerative medicine, immunotherapy and drug delivery. In the context of nanomedicines activated by near infrared (NIR) photodynamic processes (photonanomedicines; PNMs), biomimetic nanotechnology is pushing the boundaries of activatable tumor targeted nanoscale drug delivery systems. This review discusses how, by harnessing a unique collective of biological processes critical to targeting of solid tumors, biomimetic PNMs (bPNMs) can impart tumor cell specific and tumor selective photodynamic therapy-based combination regimens. Through molecular immune evasion and self-recognition, bPNMs can confer both tumor selectivity (preferential bulk tumor accumulation) and tumor specificity (discrete molecular affinity for cancer cells), respectively. They do so in a manner that is akin, yet arguably superior, to synthetic molecular-targeted PNMs. A particular emphasis is made on how bPNMs can be engineered to circumvent tumor cell heterogeneity, which is considered the Achilles’ heel of molecular targeted therapeutics. Forward-looking propositions are also presented on how patient tumor heterogeneity can ultimately be recapitulated to fabricate patient-specific, heterogeneity-targeting bPNMs. Full article

(This article belongs to the Special Issue Drug Delivery in Photodynamic Therapy (PDT))

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17 pages, 1703 KiB

Open AccessReview

Photodynamic Therapy as an Oxidative Anti-Tumor Modality: Negative Effects of Nitric Oxide on Treatment Efficacy

by Albert W. Girotti, Jonathan M. Fahey and Mladen Korbelik

Pharmaceutics 2021, 13(5), 593; https://doi.org/10.3390/pharmaceutics13050593 - 21 Apr 2021

Cited by 6 | Viewed by 2084

Abstract

Anti-tumor photodynamic therapy (PDT) is a unique oxidative stress-based modality that has proven highly effective on a variety of solid malignancies. PDT is minimally invasive and generates cytotoxic oxidants such as singlet molecular oxygen (¹O₂). With high tumor site-specificity [...] Read more.

Anti-tumor photodynamic therapy (PDT) is a unique oxidative stress-based modality that has proven highly effective on a variety of solid malignancies. PDT is minimally invasive and generates cytotoxic oxidants such as singlet molecular oxygen (¹O₂). With high tumor site-specificity and limited off-target negative effects, PDT is increasingly seen as an attractive alternative or follow-up to radiotherapy or chemotherapy. Nitric oxide (NO) is a short-lived bioactive free radical molecule that is exploited by many malignant tumors to promote cell survival, proliferation, and metastatic expansion. Typically generated endogenously by inducible nitric oxide synthase (iNOS/NOS2), low level NO can also antagonize many therapeutic interventions, including PDT. In addition to elevating resistance, iNOS-derived NO can stimulate growth and migratory aggressiveness of tumor cells that survive a PDT challenge. Moreover, NO from PDT-targeted cells in any given population is known to promote such aggressiveness in non-targeted counterparts (bystanders). Each of these negative responses to PDT and their possible underlying mechanisms will be discussed in this chapter. Promising pharmacologic approaches for mitigating these NO-mediated responses will also be discussed. Full article

(This article belongs to the Special Issue Drug Delivery in Photodynamic Therapy (PDT))

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