Handbook Of Photodynamic Therapy: Updates On Recent Applications Of Porphyrin-based Compounds

Updates on Recent Applications of Porphyrin-Based Compounds

Ravindra K Pandey, David Kessel;Thomas J Dougherty

• Publisher: WSPC
• Year: 2016
• ISBN:
  9789814719667
• Topic: Ciencias físicas
• Subtopic: Química orgánica

The main objective of this book is to present the recent applications of photodynamic therapy (PDT) in treating cancer and other diseases. The limitations associated with current PDT agents, and the synthetic designs that have been used in various laboratories are also discussed. The utility of certain tumor-avid agent for cancer imaging (fluorescence, PET, MRI) is also summarized. The book also includes the use of delivery vehicles, including nanoparticles in improving the tumor-specificity of the desired agents. The book is basically focused on the translational approach of drug development. By providing certain specific examples, a clear concept of moving a "product" from the bench to bed-side is also discussed.To have a clear concept of drug development the book is divided in three parts — Medicinal Chemistry, Mechanistic and Clinical studies. Each part includes the contributions from the leading scientists with extensive experience in the respective field. The handbook is assembled by renowned scientists Dr Dougherty, known as the father of PDT, Dr Kessel, well known for his contributions on mechanism of PDT and Dr Pandey for his inventions in developing improved agents for PDT and cancer-imaging.Contents:Part 1:Multifunctional Agents for Cancer-Imaging and Photodynamic Therapy: Impact of Polyacrylamide-Based Nanoplatforms (Aimee Marko, Nayan J Patel, Penny Joshi, Joseph R Missert and Ravindra K Pandey)Design and Synthesis of Photosensitizer-Peptide Conjugates for PDT (Tyrslai M Williams, Martha Sibrian-Vazquez and M Graça H Vicente)Current Developments in Using MESO-(TETRA) Substituted Porphyrins for PDT (Yasser M Shaker, Ayman M K Sweed, Claire Moylan, Luke Rogers, Aoife A Ryan, Rosine Petitdemange and Mathias O Senge)Core-Modified Porphyrins as Photosensitizers in Photodynamic Therapy (Michael R Detty)Phthalocyanines in Cancer-Imaging and Therapy (Hasrat Ali and Johan E van Lier)Molecular Phthalocyanine-Based Photosensitizers for Photodynamic Therapy (Pui-Chi Lo, Sun Y S Chow and Dennis K P Ng)Porphyrin Nanoparticles for Cancer Imaging and Phototherapy (Liyang Cui, Juan Chen and Gang Zhengg)Photodynamic Therapy Dosimetry: A TO Z (Michael S Patterson)Part 2:PDT: Death and Survival Pathways (David Kessel)Vascular Effects of Photodynamic Therapy for Tumors (Keith A Cengel, Charles B Simone and Theresa M Busch)EtNBS in Photodynamic Therapy (Nicholas H Nowell, Hsin-I Hung, Lauren A Austin and Conor L Evans)Negative Impact of Tumor-Generated Nitric Oxide on Photodynamic Therapy (Albert W Girotti)On the Use of Photodynamic Therapy, as Monotherapy or in Combination, in the Treatment of Polypoidal Choroidal Vasculopathy: An Update (Hubert van den Bergh and Patrycja Nowak-Sliwinska)Part 3:Photodynamic Therapy of Head and Neck Cancer — What's Old and What's New (Merrill A Biel)Endoscopic Photodynamic Therapy for Advanced Inoperable Esophageal Cancer (Joerg Lindenmann)PDT for Lung Cancer (Keishi Ohtani and Norihiko Ikeda)New Developments in Antimicrobial PDT (Wolfgang Bäumler)Antimicrobial Effects of Photosensitized Silicon Phthalocyanine (Pc) 4 (Minh Lam, Matthew L Dimaano, Pranab K Mukherjee, Mahmoud A Ghannoum, Nancy L Oleinick and Elma D Baron)Photofrin-PDT from Bench to Bedside: Some Lessons Learned (Julia Levy and Ed Levy)Readership: This book should be useful for oncologists, pharmacologists, chemists, biologists, physicists, and biochemists involved in cancer research, as well as graduate-level students in these disciplines.Photodynamic Therapy; Cancer Imaging; Multifunctional Agents; Nanoparticles Key Features:Rationale for drug design, especially for developing candidates for both cancer-imaging and therapyImportance of drug delivery vehicles for enhanced tumor-specificityHow to move a product from bench to bed side? Obstacles and solutions

Part 1

Chapter 1

Multifunctional Agents for Cancer-Imaging and Photodynamic Therapy: Impact of Polyacrylamide-Based Nanoplatforms

Aimee J. Marko^†, Nayan J. Patel^†, Penny Joshi^†,‡, Joseph R. Missert^†
and Ravindra K. Pandey^†,∗

^† Photodynamic Therapy Center, Cell Stress Biology,
Roswell Park Cancer Institute, Buffalo, NY14263
^‡ Department of Chemistry, Kumaun University, Nainital, India

Abstract

The work summarized in this chapter is focused on the chemical constituents of Photofrin, its limitations and the strategy to take the advantage of porphyrins and reduced porphyrin-based compounds in developing improved imaging and image-guided dual function agents. Advantages of polyacrylamide (PAA)-based nanoparticles (NPs) for enhancing the tumor-avidity are also discussed. Such an approach under proper strategies could help in developing other targeted multifunctional, biodegradable, biocompatible and non-toxic NPs for cancer-imaging and therapy, which is otherwise difficult to achieve.

1.Introduction

A. Brief History of Photodynamic Therapy

Photodynamic therapy (PDT), sometimes called photochemotherapy, is a form of therapy that uses non-toxic light-sensitive compounds which upon exposure to a specific wavelength of light become toxic to targeted malignant and other diseased cells.¹ PDT has also shown the ability to kill viruses, microbial cells and bacteria.² It is used clinically to treat a wide range of medical conditions, including treatment of acne, wet age-related macular degeneration (AMD)³ and malignant cancers,⁴ and is recognized as a treatment strategy which is both minimally invasive and minimally toxic.

While the applicability and potential of PDT has been known for over a hundred years, the development of modern PDT has been a gradual one, involving scientific progress in the fields of photobiology and cancer biology, as well as the development of modern photonic devices, such as lasers and LEDs.⁵ It was John Toth⁶ who acknowledged the importance of “photodynamic chemical effect” and supported in setting up several clinical sites in Japan where the term “radiation” had negative connotations.⁷ PDT received even greater interest as result of clinical PDT data reported by Thomas Dougherty in early 1980.⁸

The earliest recorded treatments that exploited the photosensitizer and a light source, in this case sunlight, for medical effect can be found in ancient Egyptian and Indian sources.⁹ The use of topically applied vegetable and plant substances to produce photoreactions in skin and cause a re-pigmentation of skin lesions, as seen with vitiligo and leukoderma¹⁰ has been known for a long time. The photosensitizing agents used in these ancient therapies have been characterized with modern science as belonging to the psoralen family of chemicals.¹¹ Psoralens are still in use today in PDT regimes to treat a variety of skin conditions, including vitiligo, psoriasis, neurodermatitis, eczema, cutaneous T-cell lymphoma and lichen ruber planus.

The first detailed scientific evidence that photosensitive synthetic dyes, in combination with a light source and oxygen could have potential therapeutic effect was recognized at the turn of the 20th century in the laboratory of von Tappeiner in Munich, Germany.¹² Historically, this was a time when Germany was leading the world in the industrial synthesis of dyes.

While studying the effects of acridine on paramecia cultures, Oscar Raab,¹³ a student of von Tappeiner observed a toxic effect. Raab also observed that light was necessary for the killing of paramecia cultures to take place. Subsequent work in the laboratory of von Tappeiner¹⁴ showed that oxygen was essential for the ‘photodynamic action’ — a term proposed by von Tappeiner.

With the discovery of photodynamic effects, von Tappeiner and colleagues went on to perform the first PDT trial in patients with skin carcinoma using the photosensitizer eosin.¹⁵ Out of six patients with a facial basal cell carcinoma, treated with a 1% eosin solution and a long-term exposure either to sunlight or to arc-lamp light, four patients showed total tumor resolution and a relapse-free period of 12 months.

It was only much later, when Thomas Dougherty and co-workers at Roswell Park Cancer Institute, Buffalo NY, clinically tested PDT again. In 1978, they published striking results in which they treated 113 cutaneous or subcutaneous malignant tumors and observed a total or partial resolution of 111 tumors.⁸

The active photosensitizer used in the clinical PDT trial by Dougherty was Hematoporphyrin Derivative (HpD),¹⁶ which was first characterized in 1960 by Lipson.¹⁷ In his research, Lipson’s objective was to find a diagnostic agent suitable for the detection of tumors in patients. With the discovery of HpD, Lipson went onto pioneer the use of endoscopes and HpD fluorescence to detect tumors.¹⁸ HpD derived from hematoporphyrin is a complex mixture of large number of porphyrin monomers and higher oligomers. As a mixture, it has long been considered suitable agent for tumor photodiagnosis and PDT because cancerous cells exhibit a significantly greater uptake and affinity for porphyrins compared to surrounding tissues. This important observation, which underlies the success of PDT to treat cancers, had been established by a number of scientific researchers prior to the discoveries made by Lipson. In 1924, Policard¹⁹ first revealed the diagnostic capabilities of hematoporphyrin fluorescence when he observed that ultraviolet radiation elicited red fluorescence in the sarcomas of laboratory rats. Policard hypothesized at the time that the fluorescence was associated with endogenous hematoporphyrin accumulation. In 1948, Figge with co-workers²⁰ showed in laboratory animals that porphyrins exhibit a preferential affinity for rapidly dividing cells, including malignant, embryonic, and regenerative cells, and because of this, they proposed that porphyrins should be used in the treatment of cancer. Subsequently, many scientific authors have repeated the observation that cancerous cells naturally accumulate porphyrins and have proposed a number of mechanisms to explain the reason of porphyrin-based photosensitizers’ tumor-avidity.²¹

Purified HpD, under the pharmaceutical name Photofrin, was the first PDT agent approved for clinical use in 1993 to treat a form of bladder cancer in Canada. Over the next decade, PDT received significant international attention and its clinical use was explored for various cancer indications, which lead to its approval by a number of health organizations all over the world (Table 1).

Chemically, Photofrin is a complex mixture, comprising porphyrin monomers, dimers, trimers and higher oligomers joined with ether, ester and/or carbon–carbon linkages.^22–34 The reports from several research groups, e.g., Bonnett et al. (UK), Ward et al. (Australia), Chen & Kessel et al. (USA) helped to characterize Photofrin chemically. However, the synthesis of individual dimeric, trimetic and oligomeric structures in which the hematoporphyrin or its dehydrated monomers were linked with ether, ester or C–C linkages by Pandey et al.³² at Roswell Park Cancer Institute, Buffalo ...

Table of contents

• Cover
• Halftitle
• Title
• Copyright
• Contents
• Preface
• Part 1
• Part 2
• Part 3
• Index