Targeted photodynamic therapy – a promising strategy of tumor treatment (original) (raw)
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Targeting Strategies in Photodynamic Therapy for Cancer Treatment
Handbook of Photomedicine, 2013
Despite recent advances in surgery, chemotherapy, and radiation treatment, survival of patients with advanced malignancy remains suboptimal. Photodynamic therapy is a relatively new cytotoxic treatment, predominantly used in anti-cancer approaches, that depends on the retention of photosensitizers in tumor and their activation after light exposure in the presence of molecular oxygen. Photosensitizers are photo-sensible compounds that upon photoactivation, effect strongly localized oxidative damage within the target cells. The ability to confine activation of the photosensitizer by restricting illumination to the tumor allows for a certain degree of selectivity. Nevertheless, the targeted delivery of photosensitizers to defined cells is a major challenge in photodynamic therapy of cancer, and one area of importance is photosensitizer targeting. In this sense, an arsenal of targeting strategies has been developed recently. Alterations or increased levels in receptor expression of specific cellular type occur in the diseased tissues. Therefore, photosensitizers can be covalently attached to molecules such as specific peptides, leading to a receptor-mediated targeting strategy. These active-targeting approaches may be particularly useful for vascular-targeted photodynamic therapy. The present chapter will focus on recent and significant advances and developments in targeting strategies in photodynamic therapy with the emphasis on target specificity.
Deregulation of cell growth and development lead to cancer, a severe condition that claims millions of lives worldwide. Targeted or selective approaches used during cancer treatment determine the efficacy and outcome of the therapy. In order to enhance specificity and targeting and better treatment options for cancer, novel and alternative modalities are currently under development. Photodynamic therapy has the potential to eradicate cancer and combination therapy would yield even greater outcomes. Nanomedicine-aided cancer therapy shows enhanced specificity for cancer cells and minimal side-effects coupled with effective cancer destruction both in vitro and in vivo. Nanocarriers used in drug-delivery systems are well able to penetrate cancer stem cell niche, simultaneously killing cancer cells and eradicate drug-resistant cancer stem cells, yielding therapeutic efficiency up to 100 fold against drug-resistant cancer in comparison with free drugs. Safety precautions should be consid...
Progress in Clinical Trials of Photodynamic Therapy for Solid Tumors and the Role of Nanomedicine
Cancers
Current research to find effective anticancer treatments is being performed on photodynamic therapy (PDT) with increasing attention. PDT is a very promising therapeutic way to combine a photosensitive drug with visible light to manage different intense malignancies. PDT has several benefits, including better safety and lower toxicity in the treatment of malignant tumors over traditional cancer therapy. This reasonably simple approach utilizes three integral elements: a photosensitizer (PS), a source of light, and oxygen. Upon light irradiation of a particular wavelength, the PS generates reactive oxygen species (ROS), beginning a cascade of cellular death transformations. The positive therapeutic impact of PDT may be limited because several factors of this therapy include low solubilities of PSs, restricting their effective administration, blood circulation, and poor tumor specificity. Therefore, utilizing nanocarrier systems that modulate PS pharmacokinetics (PK) and pharmacodynami...
Nano materials-based devices by photodynamic therapy for treating cancer applications
Photodynamic therapy (PDT) is a non-invasive beneficial modality that is able to be used instead of radiotherapy and chemotherapy to treat cancer. Low water solubility makes administering photosensitizers (PSs) complicated, which undermines several molecules' medicinal application, limits PDT's efficacy. Nanotechnology can be used to tune the photoactive drug's pharmacokinetics and tumor selectivity and perform a vital role in the photosensitizer's photodynamic function by maintaining the photosensitizer's monomeric structure and thereby optimizing the photochemistry that occurs upon photon absorption. Also, nanotechnology-based drug delivery systems may progress a PS's transcytosis by allowing two or different drugs to be delivered at the same time via epithelial and endothelial barriers. Based on this, nanotechnology's application in medicine could open up a slew of novel cancer treatment possibilities while also improving the efficacy of presently available medicines. Consequently, this research aims to investigate nanotechnology-based medication conveyance instruments utilized for photodynamic cancer treatment.
Biomodulatory approaches to photodynamic therapy for solid tumors
Cancer Letters, 2012
Photodynamic Therapy (PDT) uses a photosensitizing drug in combination with visible light to kill cancer cells. PDT has an advantage over surgery or ionizing radiation because PDT can eliminate tumors without causing fibrosis or scarring. Disadvantages include the dual need for drug and light, and a generally lower efficacy for PDT versus surgery. This minireview describes basic principles of PDT, photosensitizers available, and aspects of tumor biology that may provide further opportunities for treatment optimization. An emerging biomodulatory approach, using methotrexate or Vitamin D in combination with aminolevulinate-based PDT, is described. Finally, current clinical uses of PDT for solid malignancies are reviewed.
Ligand-Targeted Delivery of Photosensitizers for Cancer Treatment
Molecules
Photodynamic therapy (PDT) is a promising cancer treatment which involves a photosensitizer (PS), light at a specific wavelength for PS activation and oxygen, which combine to elicit cell death. While the illumination required to activate a PS imparts a certain amount of selectivity to PDT treatments, poor tumor accumulation and cell internalization are still inherent properties of most intravenously administered PSs. As a result, common consequences of PDT include skin photosensitivity. To overcome the mentioned issues, PSs may be tailored to specifically target overexpressed biomarkers of tumors. This active targeting can be achieved by direct conjugation of the PS to a ligand with enhanced affinity for a target overexpressed on cancer cells and/or other cells of the tumor microenvironment. Alternatively, PSs may be incorporated into ligand-targeted nanocarriers, which may also encompass multi-functionalities, including diagnosis and therapy. In this review, we highlight the major...
In Vivo Studies of Nanostructure-Based Photosensitizers for Photodynamic Cancer Therapy
Small, 2014
A nimal models, particularly rodents, are major translational models for evaluating novel anticancer therapeutics. In this review, different types of nanostructure-based photosensitizers that have advanced into the in vivo evaluation stage for the photodynamic therapy (PDT) of cancer are described. This article focuses on the in vivo effi cacies of the nanostructures as delivery agents and as energy transducers for photosensitizers in animal models. These materials are useful in overcoming solubility issues, lack of tumor specifi city, and access to tumors deep in healthy tissue. At the end of this article, the opportunities made possible by these multiplexed nanostructure-based systems are summarized, as well as the considerable challenges associated with obtaining regulatory approval for such materials. The following questions are also addressed: (1) Is there a pressing demand for more nanoparticle materials? (2) What is the prognosis for regulatory approval of nanoparticles to be used in the clinic?
Developing Activatable Photosensitizers for Fluorescence-Guided Photodynamic Therapy
2019
Photodynamic therapy (PDT) is increasingly being recognized as an attractive alternative to conventional forms of cancer therapies. Already clinically approved, this procedure is minimally invasive; by combining light, a small-molecule photosensitizer (PS), and molecular oxygen, reactive oxygen species can be produced in situ, causing damage to vital cellular components. Subsequently, cell death occurs by apoptosis or necrosis. In practice, after a PS has been administered, an appropriate wavelength of light is irradiated at tumors and surrounding tissue. However, since PSs lack selectivity and non-specifically localize, light irradiation also destroys neighboring healthy cells. To this regard, I developed activatable-PSs that extend beyond the conventional two-layered selectivity inherent to PDT by including biomarker-specific activation with enzymes: Glutathione S-Transferase, Carboxylesterase 2, and Azoreductase. With this heightened control, these PDT beacons will give a highly specific and localized therapeutic response by unquenching the probe to restore the PS's native properties at the target site.
Strategies for Enhanced Photodynamic Therapy Effects
Photochemistry and Photobiology, 2007
Photodynamic therapy (PDT) is a treatment modality for the selective destruction of cancerous and nonneoplastic pathologies that involves the simultaneous presence of light, oxygen and a light-activatable chemical called a photosensitizer (PS) to achieve a cytotoxic effect. The photophysics and mechanisms of cell killing by PDT have been extensively studied in recent years, and PDT has received regulatory approval for the treatment of a number of diseases worldwide. As the application of this treatment modality expands with regard to both anatomical sites and disease stages, it will be important to develop strategies for enhancing PDT outcomes. This article focuses on two broad approaches for PDT enhancement: