Nanoscintillator-Based X-Ray-Induced Photodynamic Therapy.

Photodynamic therapy (PDT) is an emerging treatment option for cancer. In PDT, photosensitizers are delivered to tumors and stimulated by light to generate reactive oxygen species (ROS)-most importantly singlet oxygen (1O2)-to damage tumor cells or induce tissue ischemia. PDT is associated with a low level of systemic toxicity because photosensitizers are usually pharmaceutically inactive in the dark and photoirradiation is applied only to tumor areas in the procedure. Additionally, PDT can be applied repeatedly without cumulative toxicity or incurring resistance, and may stimulate systemic anti-tumor immunity. However, PDT's clinical use has been restricted due to the limited penetration of visible light through tissues. X-rays possess superior tissue penetration capability and are exploited in X-ray-induced photodynamic therapy to overcome this limitation. Herein we have demonstrated this principle with a novel LiGa5O8:Cr (LGO:Cr)-based nanoscintillator which emits near-infrared X-ray luminescence to both guide external beam therapy and induce PDT with the photosensitizer (2,3-naphthalocyanine) encapsulated in a mesoporous silica shell of the nanoscintillator.

Potassium Iodide Nanoparticles Enhance Radiotherapy against Breast Cancer by Exploiting the Sodium-Iodide Symporter.

Iodine has shown promise in enhancing radiotherapy. However, conventional iodine compounds show fast clearance and low retention inside cancer cells, limiting their application as a radiosensitizer. Herein, we synthesize poly(maleic anhydride-alt-1-octadecene) coated KI nanoparticles (PMAO-KI NPs) and evaluate their potential for enhancing radiotherapy. Owing to the polymer coating, the KI core of PMAO-KI NPs is not instantly dissolved in aqueous solutions but slowly degraded, allowing for controlled release of iodide (I-). I- is transported into cells via the sodium iodide symporter (NIS), which is upregulated in breast cancer cells. Our results show that PMAO-KI NPs can enhance radiation-induced production of reactive oxygen species such as hydroxyl radicals. When tested in vitro with MCF-7 cells, PMAO-KI NPs promote radiation-induced DNA double-strand breaks and lipid peroxidation, causing a drop in cancer cell viability and reproductivity. When tested in MCF-7 bearing mice, PMAO-KI NPs show significant radiosensitizing effects, leading to complete tumor eradication in 80% of the treated animals without inducing additional toxicity. Overall, our strategy exploits electrolyte nanoparticles to deliver iodide into cancer cells through NIS, thus promoting radiotherapy against breast cancer.

Correction: The effect of light wavelength on in vitro bilirubin photodegradation and photoisomer production.

Following publication of this article, the authors noticed that an incorrect affiliation was assigned to the author "Lucie Muchová". The original article has now been updated so that the author "Lucie Muchová" is associated with the "Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University, Katerinská 32, 120 00 Prague, Czech Republic". This has been corrected in both the PDF and HTML versions of the article.

The effect of light wavelength on in vitro bilirubin photodegradation and photoisomer production.

BACKGROUND: The action spectrum for bilirubin photodegradation has been intensively studied. However, questions still remain regarding which light wavelength most efficiently photodegrades bilirubin. In this study, we determined the in vitro effects of different irradiation wavelength ranges on bilirubin photodegradation. METHODS: In our in vitro method, normalized absolute irradiance levels of 4.2 × 1015 photons/cm2/s from light-emitting diodes (ranging from 390-530 nm) and 10-nm band-pass filters were used to irradiate bilirubin solutions (25 mg/dL in 4% human serum albumin). Bilirubin and its major photoisomer concentrations were determined; the half-life time of bilirubin (t1/2) was calculated for each wavelength range, and the spectral characteristics for bilirubin photodegradation products were obtained for key wavelengths. RESULTS: The in vitro photodegradation of bilirubin at 37 °C decreased linearly as the wavelength was increased from 390 to 500 nm with t1/2 decreasing from 63 to 17 min, respectively. At 460 ± 10 nm, a significantly lower rate of photodegradation and thus higher t1/2 (31 min) than that at 500 nm (17 min) was demonstrated. CONCLUSION: In our system, the optimum bilirubin photodegradation and lumirubin production rates occurred between 490 and 500 nm. Spectra shapes were remarkably similar, suggesting that lumirubin production was the major process of bilirubin photodegradation.

Nanoparticles to mediate X-ray-induced photodynamic therapy and Cherenkov radiation photodynamic therapy.

Photodynamic therapy (PDT) has emerged as an attractive option for cancer treatment. However, conventional PDT is activated by light that has poor tissue penetration depths, limiting its applicability in the clinic. Recently the idea of using X-ray sources to activate PDT and overcome the shallow penetration issue has garnered significant interest. This can be achieved by external beam irradiation and using a nanoparticle scintillator as transducer. Alternatively, research on exploiting Cherenkov radiation from radioisotopes to activate PDT has also begun to flourish. In either approach, the most auspicious success is achieved using nanoparticles as either a scintillator or a photosensitizer to mediate energy transfer and radical production. Both X-ray induced PDT (X-PDT) and Cherenkov radiation PDT (CR-PDT) contain a significant radiation therapy (RT) component and are essentially PDT and RT combination. Unlike the conventional combination, however, in X-PDT and CR-PDT, one energy source simultaneously activates both processes, making the combination always in synchronism and the synergy potential maximized. While still in early stage of development, X-PDT and CR-PDT address important issues in the clinic and hold great potential in translation. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Phototherapy device effectiveness in Nigeria: irradiance assessment and potential for improvement.

This study investigated the effectiveness of simple-to-implement adjustments of phototherapy devices on irradiance levels in a cross-section of Nigerian hospitals. A total of 76 phototherapy devices were evaluated in 16 hospitals while adjustments were implemented for a subset of 25 devices for which consent was obtained. The mean irradiance level was 7.6 ± 5.9 µW/cm(2)/nm for all devices prior to adjustments. The average irradiance level improved from 9.0 µW/cm(2)/nm to 27.3 µW/cm(2)/nm for the adjusted group (n = 25) compared with 6.8 ± 5.4 µW/cm(2)/nm for the unadjusted group (n = 51). Simple, inexpensive adjustments to phototherapy devices with sub-optimal irradiance levels can significantly improve their effectiveness to acceptable international standards and should be widely promoted in resource-constrained settings.

The need to implement effective phototherapy in resource-constrained settings.

Phototherapy is the treatment of choice to reduce the severity of neonatal unconjugated hyperbilirubinemia regardless of its etiology. Its implementation requires a technical framework that conforms to existing evidence-based guidelines that promote its safer and effective use worldwide. Optimal use of phototherapy has been defined by specific ranges of total serum bilirubin thresholds configured to an infant's postnatal age (in hours) and potential risk for bilirubin neurotoxicity. Effective phototherapy implies its use at specific blue light wavelengths (peak emission, 450 ± 20 nm) and emission spectrum (range, 400-520 nm), preferably in a narrow bandwidth that is delivered at an irradiance of ≥30 µW/cm(2)/nm to up to 80% of an infant's body surface area. However, this is often not feasible in clinical settings with limited or constrained resources. To identify and bridge implementation barriers, we propose minimum criteria for device performance for safe and practical use of phototherapy as a prophylactic intervention to prevent severe hyperbilirubinemia.