Chemical approaches for the enhancement of 5-aminolevulinic acid-based photodynamic therapy and photodiagnosis

Abstract

The development of photodynamic therapy and photodiagnosis with 5-aminolevulinic acid presents a number of challenges that can be addressed by applying chemical insight and a range of novel prodrug strategies.

In order for the light to shine so brightly, the darkness must be present—why do cancers fluoresce with 5-aminolaevulinic acid?

“…5-ALA is currently licensed by the FDA for the photodynamic treatment of dermatological conditions such as actinic keratoses, squamous and basal cell carcinomas and, more recently, in the tumour resection of high-grade gliomas. 81 There are a number of studies and ongoing clinical trials using 5-ALA for the diagnosis and treatment of cancers including those of the bladder, female reproductive tract, prostate and brain, all of which have been extensively reviewed by van Straten et al 5 To overcome issues such as bioavailability and solubility, derivatives of 5-ALA have been developed (extensively reviewed by Tewari and Eggleston 82 ) and shown to be successful in vivo. For example, hexyl-aminolaevulinate (HAL), a hexyl ester of 5-ALA, has been approved for endoscopic detection of bladder cancer in Europe and the USA since 2005.…”

“…To overcome issues such as bioavailability and solubility, derivatives of 5-ALA have been developed (extensively reviewed by Tewari and Eggleston 82 ) and shown to be successful in vivo. For example, hexyl-aminolaevulinate (HAL), a hexyl ester of 5-ALA, has been approved for endoscopic detection of bladder cancer in Europe and the USA since 2005.…”

Photodynamic diagnosis and photodynamic therapy of colorectal cancer in vitro and in vivo

“…5-Aminolevulinicacid (5-ALA), is a biosynthetic precursor of the PS protoporphyrin IX (PpIX), it has been utilized within PDD applications for various cancers, owing to its unique photoproperties, which allow for it to be activated at short and long wavelengths, thus allowing it to be used for both diagnostic and PDT cancer treatment applications. 59,60 Various studies have elucidated that PpIX exhibits two particular emission of peaks; one at 405 nm emitting blue illumination for PDD diagnosis and one at 633 nm emitting red visible light for PDT treatment of malignant or premalignant tumors. 29,61,62 Within a study performed by Nakamura et al (2015), ten patients with early-stage gastric/colorectal tumors were given 20 mg kg À1 of 5-ALA enteric-coated capsules orally.…”

Drug Delivery Systems for Phthalocyanines for Photodynamic Therapy

“…This compound shows low toxicity and is rapidly cleared from the body by the existing clearance mechanism. In addition, PpIX-induced fluorescence can be visualized under blue light and can be employed in diagnosis (3,(94)(95)(96)(97)(98).…”