Photodynamic therapy in lung cancer. A review - ScienceDirect

Journal of Photochemistry and Photobiology B: Biology

Volume 36, Issue 2, November 1996, Pages 199-204

Journal of Photochemistry and Photobiology B: Biology

https://doi.org/10.1016/S1011-1344(96)07372-1 Get rights and content

Abstract

Photodynamic therapy (PDT) in lung cancer was introduced in 1980 to treat tumours located in the major airways. After systemic injection of photosensitizers, tumour illumination is performed using a laser fibre to transmit light of a specific wavelength. PDT can be performed under local anaesthesia using the flexible fibreoptic bronchoscope. Skin photosensitivity is the most important treatment morbidity caused by the prolonged cutaneous retention of photosensitizer molecules.

Ample data have shown that PDT is effective in obtaining tumour necrosis, but the skin photosensitivity issue limits its palliative potential. Moreover, competing bronchoscopic techniques, such as electrosurgery, Nd-YAG laser and and brachytherapy, are available and seem to be equally palliative for the debulking of intraluminal obstructive lung tumours.

The curative potential of PDT in patients with roentgenologically occult lung cancer is the most interesting aspect of this treatment modality. A significant number of patients with lung cancer have limited pulmonary function. A normal tissue sparing treatment such as PDT may provide an alternative, as patients may also have subsequent, multiple lung cancer primaries.

Since early lung cancer detection is now becoming feasible, PDT may be applied to treat roentgenologically occult tumours with curative intent. This may optimize treatment efficacy in the n ear future.

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In this chapter, we provide a comprehensive review of the pathogenesis, features, diagnostic evaluation, management, survival, and complications from lung metastasis. Lung metastasis may arise due to a combination of dietary influences, genetic and immunologic changes using normal cellular processes to assist in metastatic spread. Computed tomography with or without positron emission tomography is most frequently used to detect lung metastases since MRI is less sensitive than these modalities. Patients with isolated or oligometastatic disease can be considered for definitive management, including radiofrequency ablation (RFA), stereotactic radiation therapy, and surgical resection with non-surgical interventions typically offered for unresectable tumors or poor surgical candidates. Primary tumor types that commonly have lung metastasis include colon carcinoma, renal cell carcinoma, sarcoma, melanoma, head and neck squamous cell carcinoma, germ cell tumors, breast cancer, and giant cell tumor of bone, and survival after treatment is highly dependent on the primary site. Common complications of metastatic disease include malignant pleural effusions, managed with indwelling catheters or sclerotic agents, and bronchial obstructions, managed with endobronchial stenting, photodynamic therapy, and radiation therapy.
Development and evaluation of hyaluronic acid-based polymeric micelles for targeted delivery of photosensitizer for photodynamic therapy in vitro
2018, Journal of Drug Delivery Science and Technology
Citation Excerpt :
Lung cancer, the most common cause of cancer deaths worldwide was one of the first indications for PDT [2]. In the early 1980s, PDT was introduced in human lung cancer therapy [3], and it is now adopted as an alternative treatment for patients for whom surgery is contraindicated [4]. Protoporphyrin IX (PpIX) is a PS that is endogenously produced by the heme biosynthetic pathway.
To enhance the effectiveness and specificity of photodynamic therapy (PDT) in CD44-overexpressing cancers, the hyaluronic acid-b-poly (d,l-lactide-co-glycolide) copolymer (HA-b-PLGA) was synthesized, and potent photosensitizer protoporphyrin IX (PpIX) loaded polymeric micelles were prepared. The formulation organic solvent, polymer concentration, and feeding weight ratio of PpIX to polymer were optimized. PpIX-loaded HA-b-PLGA micelles (PpIX HA-PLGA micelles) were obtained with a drug loading rate of 2%, encapsulation efficiency of 43%, average diameter of 213 nm and zeta potential of −24 mV. The PpIX HA-PLGA micelles exhibited enhanced phototoxicity toward A549 cells. A cellular uptake study indicated that the micelles were internalized by CD44-mediated endocytosis. Exposure of A549 cell spheroids to HA-PLGA micelles showed deeper penetration and improved phototoxicity compared with nanoparticle and free drug analogues. PpIX HA-PLGA micelles have great potential for CD44-targeting delivery in PDT treatment.
Effects of continuous wave and fractionated diode laser on human fibroblast cancer and dermal normal cells by zinc phthalocyanine in photodynamic therapy: A comparative study
2016, Journal of Photochemistry and Photobiology B: Biology
In this experimental study, cancer and normal cells behavior during an in vitro photodynamic therapy (PDT) under exposure of continuous wave (CW) and fractionated mode of laser with different irradiation power and time intervals was compared and investigated. At the first, human fibroblast cancer cell line (SW 872) and human dermal normal (HFFF2) cell line were incubated with different concentrations of zinc phthalocyanine (ZnPc), as a PDT drug. The cells, then, were irradiated with a 675 nm diode laser and the cell viability was evaluated using MTT assay.
Under optimized conditions, the viability of the cancer cells was eventually reduced to 3.23% and 13.17%, and that of normal cells was decreased to 20.83% and 36.23% using CW and fractionated diode lasers, respectively. In general, the ratio of ZnPc LD₅₀ values for the normal cells to the cancer cells with CW laser was much higher than that of the fractionated laser. Subsequently, cancer cells in comparison with normal ones were found to be more sensitive toward the photodynamic damage induced by ZnPc. In addition, treatment with CW laser was found to be more effective against the cancer cells with a lower toxicity to the normal cells compared with the fractionated diode laser.
Hypocrellin B and paclitaxel-encapsulated hyaluronic acid-ceramide nanoparticles for targeted photodynamic therapy in lung cancer
2016, Journal of Photochemistry and Photobiology B: Biology
Citation Excerpt :
In such situation, non-invasive PDT is required. PDT for human lung cancer was introduced in the early 1980s [6] and it was one of the first indications for PDT [7]. The process of PDT in various cancers has been introduced by previous studies [8–10].
To increase the therapeutic efficacy of photodynamic therapy (PDT) in treating lung cancer, we developed both photosensitizer and anticancer drug encapsulated hyaluronic acid–ceramide nanoparticles. Based on our previous study, a co-delivery system of photosensitizers and anticancer agents greatly improves the therapeutic effect of PDT. Furthermore, hyaluronic acid–ceramide-based nanoparticles are ideal targeting carriers for lung cancer.
In vitro phototoxicity in A549 (human lung adenocarcinoma) cells and in vivo antitumor efficacy in A549 tumor-bearing mice treated with hypocrellin B (HB)-loaded nanoparticles (HB-NPs) or hypocrellin B and paclitaxel loaded nanoparticles (HB–P-NPs) were evaluated.
Cell viability assay, microscopic analysis and FACS analysis were performed for the in vitro studies and HB–P-NPs showed enhanced phototoxicity compared with HB-NPs. In the animal study, the tumor volume change and the histological analysis was studied and the anticancer efficacy improved in the order of free HB < HB-NPs < HB–P-NPs.
In conclusion, the combination therapy of PDT and chemotherapy, and hyaluronic acid–ceramide nanoparticle-based targeted delivery improved the effects of PDT in lung cancer in mice.
The in vitro photodynamic effect of laser activated gallium, indium and iron phthalocyanine chlorides on human lung adenocarcinoma cells
2013, Journal of Photochemistry and Photobiology B: Biology
Citation Excerpt :
The procedure is relatively simple and treatment does not require the cutting through ribs, nerves and healthy lung parenchyma tissue; making it less invasive than conventional surgery [1,2]. High risk patients with poor pulmonary and/or cardiac function that have been refused surgery and suffer from multiple lung cancers become ideal candidates for PDT treatment [3]. Due to the fact that treatment involves the systemic administration of a cancerous tissue photosensitizing drug (photosensitiser; PS) such as porfimer sodium (Photofrin®) and photoirradiation through a fibreoptic bronchoscope.
Metal-based phthalocyanines currently are utilized as a colorant for industrial applications but their unique properties also make them prospective photosensitizers. Photosensitizers are non-toxic drugs, which are commonly used in photodynamic therapy (PDT), for the treatment of various cancers. PDT is based on the principle that, exposure to light shortly after photosensitizer administration predominately leads to the production of reactive oxygen species for the eradication of cancerous cells and tissue. This in vitro study investigated the photodynamic effect of gallium (GaPcCl), indium (InPcCl) and iron (FePcCl) phthalocyanine chlorides on human lung adenocarcinoma cells (A549). Experimentally, 2 × 10⁴ cells/ml were seeded in 24-well tissue culture plates and allowed to attach overnight, after which cells were treated with different concentrations of GaPcCl, InPcCl and FePcCl ranging from 2 μg/ml to 100 μg/ml. After 2 h, cells were irradiated with constant light doses of 2.5 J/cm², 4.5 J/cm² and 8.5 J/cm² delivered from a diode laser (ʎ = 661 nm). Post-irradiated cells were incubated for 24 h before cell viability was measured using the MTT Assay. At 24 h after PDT, irradiation with a light dose of 2.5 J/cm² for each photosensitizing concentration of GaPcCl, InPcCl and FePcCl produced a significant decrease in cell viability, but when the treatment light dose was further increased to 4.5 J/cm² and 8.5 J/cm² the cell survival was less than 40%. Results also showed that photoactivated FePcCl decreased cell survival of A549 cells to 0% with photosensitizing concentrations of 40 μg/ml and treatment light dose of 2.5 J/cm². A 20 μg/ml photosensitizing concentration of FePcCl in combination with an increased treatment light dose of either 4.5 J/cm² or 8.5 J/cm² also resulted in 0% cell survival. This PDT study concludes that low concentrations on GaPcCl, InPcCl and FePcCl activated with low level light doses can be used for the effective in vitro killing of lung cancer cells.
Interaction of amphiphilic chlorin-based photosensitizers with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine monolayers
2009, Chemistry and Physics of Lipids
The drawbacks of the presently used photosensitizers include their relatively low selectivity toward cancer cells, and long-lasting accumulation in healthy tissues. Our recent results indicate that conjugating a photosensitizer with folic acid both enhances the active uptake by cells, and decreases the accumulation in healthy tissue. Here, the interaction between 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) monolayers used as model membranes, and three different photosensitizers were studied; the derivatives were the non-conjugated meta-tetrahydroxyphenylchlorin (m-THPC, CHL1) and tris(3-hydroxyphenyl)-4-carboxyphenylchlorin (CHL2), as well as a folic acid-conjugated m-THPC-like molecule (CHL3). The results obtained indicate that the folate moiety present in the conjugated derivative CHL3 is involved in the interaction with the phospholipid polar heads. This interaction may be responsible for a better miscibility of CHL3 with the DPPC films compared to CHL1 and CHL2, while elimination of CHL3 from the tissue may be due rather to specific, biological processes and not to its polarity.

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