scholarly journals Radiodynamic Therapy Using TAT Peptide-Targeted Verteporfin-Encapsulated PLGA Nanoparticles

2021 ◽  
Vol 22 (12) ◽  
pp. 6425
Author(s):  
Sandhya Clement ◽  
Ayad G. Anwer ◽  
Layla Pires ◽  
Jared Campbell ◽  
Brian C. Wilson ◽  
...  

Radiodynamic therapy (RDT) is a recent extension of conventional photodynamic therapy, in which visible/near infrared light irradiation is replaced by a well-tolerated dose of high-energy X-rays. This enables greater tissue penetration to allow non-invasive treatment of large, deep-seated tumors. We report here the design and testing of a drug delivery system for RDT that is intended to enhance intra- or peri-nuclear localization of the photosensitizer, leading to DNA damage and resulting clonogenic cell kill. This comprises a photosensitizer (Verteporfin, VP) incorporated into poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) that are surface-functionalized with a cell-penetrating HIV trans-activator of transcription (TAT) peptide. In addition to a series of physical and photophysical characterization studies, cytotoxicity tests in pancreatic (PANC-1) cancer cells in vitro under 4 Gy X-ray exposure from a clinical 6 MV linear accelerator (LINAC) showed that TAT targeting of the nanoparticles markedly enhances the effectiveness of RDT treatment, particularly when assessed by a clonogenic, i.e., DNA damage-mediated, cell kill.

2020 ◽  
Vol 9 (2) ◽  
pp. 420
Author(s):  
Ana Marmaneu-Menero ◽  
José Enrique Iranzo-Cortés ◽  
Teresa Almerich-Torres ◽  
José Carmelo Ortolá-Síscar ◽  
José María Montiel-Company ◽  
...  

The objective of the study is to analyse the available evidence for the validity of the transillumination method in the diagnosis of interproximal caries. Bibliographic searches were carried out in three data bases (PubMed, Embase, Scopus) with the key words “Transillumination AND caries”. A total of 11 studies were selected for the qualitative analysis and meta-analysis. In the qualitative analysis, both in vivo and in vitro studies were included. The gold standards were tomography, digital radiography, and clinical visual diagnosis. The meta-analysis determined the sensitivity, specificity, and area below the ROC curve relative to the transillumination method in the diagnosis of caries in dentine. Meta-analysis results obtained for transillumination gave a sensitivity value of 0.69 (confidence interval: 0.54–0.81), a specificity value of 0.89 (confidence interval: 0.61–0.98), while giving an AUC value of 0.79 (confidence interval: 0.67–0.87). Transillumination is a method offering moderate validity in the diagnosis of carious lesions in dentine, there is no strong evidence that may enable us to affirm that transillumination may fully substitute X-rays in the complementary diagnosis of carious lesions


2014 ◽  
Vol 136 (2) ◽  
Author(s):  
Matthew R. DeWitt ◽  
Allison M. Pekkanen ◽  
John Robertson ◽  
Christopher G. Rylander ◽  
Marissa Nichole Rylander

Single-walled carbon nanohorns (SWNHs) have significant potential for use in photothermal therapies due to their capability to absorb near infrared light and deposit heat. Additionally, their extensive relative surface area and volume makes them ideal drug delivery vehicles. Novel multimodal treatments are envisioned in which laser excitation can be utilized in combination with chemotherapeutic-SWNH conjugates to thermally enhance the therapeutic efficacy of the transported drug. Although mild hyperthermia (41–43 °C) has been shown to increase cellular uptake of drugs such as cisplatin (CDDP) leading to thermal enhancement, studies on the effects of hyperthermia on cisplatin loaded nanoparticles are currently limited. After using a carbodiimide chemical reaction to attach CDDP to the exterior surface of SWNHs and nitric acid to incorporate CDDP in the interior volume, we determined the effects of mild hyperthermia on the efficacy of the CDDP-SWNH conjugates. Rat bladder transitional carcinoma cells were exposed to free CDDP or one of two CDDP-SWNH conjugates in vitro at 37 °C and 42 °C with the half maximal inhibitory concentration (IC50) for each treatment. The in vitro results demonstrate that unlike free CDDP, CDDP-SWNH conjugates do not exhibit thermal enhancement at 42 °C. An increase in viability of 16% and 7% was measured when cells were exposed at 42 deg compared to 37 deg for the surface attached and volume loaded CDDP-SWNH conjugates, respectively. Flow cytometry and confocal microscopy showed a decreased uptake of CDDP-SWNH conjugates at 42 °C compared to 37 °C, revealing the importance of nanoparticle uptake on the CDDP-SWNH conjugate's efficacy, particularly when hyperthermia is used as an adjuvant, and demonstrates the effect of particle size on uptake during mild hyperthermia. The uptake and drug release studies elucidated the difference in viability seen in the drug efficacy studies at different temperatures. We speculate that the disparity in thermal enhancement efficacy observed for free drug compared to the drug SWNH conjugates is due to their intrinsic size differences and, therefore, their mode of cellular uptake: diffusion or endocytosis. These experiments indicate the importance of tuning properties of nanoparticle-drug conjugates to maximize cellular uptake to ensure thermal enhancement in nanoparticle mediated photothermal-chemotherapy treatments.


Mutagenesis ◽  
2019 ◽  
Vol 34 (5-6) ◽  
pp. 431-431
Author(s):  
José M Enciso ◽  
Kristine B Gutzkow ◽  
Gunnar Brunborg ◽  
Ann-Karin Olsen ◽  
Adela López de Cerain ◽  
...  

2021 ◽  
Author(s):  
Daniel DiCenzo DiCenzo

Gold nanoparticles (GNP) have been shown to highly absorb ionizing radiation compared to tissue. GNPs have also been shown to be high absorbers of non-ionizing radiation with a peak absorbance at a wavelength dependent on their shape and size. This study investigated radiation dose enhancement in PC3 cells when in the presence of gold nanorods (NR) and near infrared light (IR). The PC3 cells were incubated with either PEGylated NRs (PNR) or anti prostate stem cell antigen antibody with nuclear localization sequence peptide conjugated NRs (AbNR). They were exposed to near infrared light at a wavelength of 810 nm to achieve a temperature of 42 ºC to 43 ºC for 60 minutes. They were also exposed to 160 kVp x-rays. It was found that both targeted and non-targeted GNPs when exposed to radiation and near infrared light synergistically enhanced radiation dose. It was also found that AbNRs provide greater dose enhancement than PNRs.


2019 ◽  
Vol 18 ◽  
pp. 153303381987130
Author(s):  
Francois Chevalier ◽  
Dounia Houria Hamdi ◽  
Charlotte Lepleux ◽  
Mihaela Temelie ◽  
Anaïs Nicol ◽  
...  

Chondrosarcomas are malignant tumors of the cartilage that are chemoresistant and radioresistant to X-rays. This restricts the treatment options essential to surgery. In this study, we investigated the sensitivity of chondrosarcoma to X-rays and C-ions in vitro. The sensitivity of 4 chondrosarcoma cell lines (SW1353, CH2879, OUMS27, and L835) was determined by clonogenic survival assays and cell cycle progression. In addition, biomarkers of DNA damage responses were analyzed in the SW1353 cell line. Chondrosarcoma cells showed a heterogeneous sensitivity toward irradiation. Chondrosarcoma cell lines were more sensitive to C-ions exposure compared to X-rays. Using D10 values, the relative biological effectiveness of C-ions was higher (relative biological effectiveness = 5.5) with cells resistant to X-rays (CH2879) and lower (relative biological effectiveness = 3.7) with sensitive cells (L835). C-ions induced more G2 phase blockage and micronuclei in SW1353 cells as compared to X-rays with the same doses. Persistent unrepaired DNA damage was also higher following C-ions irradiation. These results indicate that chondrosarcoma cell lines displayed a heterogeneous response to conventional radiation treatment; however, treatment with C-ions irradiation was more efficient in killing chondrosarcoma cells, compared to X-rays.


2020 ◽  
Vol 6 (44) ◽  
pp. eabb6165
Author(s):  
Lukas Pfeifer ◽  
Nong V. Hoang ◽  
Maximilian Scherübl ◽  
Maxim S. Pshenichnikov ◽  
Ben L. Feringa

Light-controlled artificial molecular machines hold tremendous potential to revolutionize molecular sciences as autonomous motion allows the design of smart materials and systems whose properties can respond, adapt, and be modified on command. One long-standing challenge toward future applicability has been the need to develop methods using low-energy, low-intensity, near-infrared light to power these nanomachines. Here, we describe a rotary molecular motor sensitized by a two-photon absorber, which efficiently operates under near-infrared light at intensities and wavelengths compatible with in vivo studies. Time-resolved spectroscopy was used to gain insight into the mechanism of energy transfer to the motor following initial two-photon excitation. Our results offer prospects toward in vitro and in vivo applications of artificial molecular motors.


Nanomedicine ◽  
2020 ◽  
Vol 15 (3) ◽  
pp. 219-234 ◽  
Author(s):  
Isabel Ortiz de Solorzano ◽  
Martin Prieto ◽  
Gracia Mendoza ◽  
Victor Sebastian ◽  
Manuel Arruebo

Aim: Developing hybrid poly(N-isopropylacrylamide)-based nanogels decorated with plasmonic hollow gold nanoparticles for on-demand drug delivery and their physico-chemical characterization, bupivacaine loading and release ability upon light irradiation, and in vitro cell viability. Materials & methods: Hollow gold nanoparticles were prepared by galvanic replacement reaction; poly(N-isopropylacrylamide)-based nanogels were synthesized via precipitation polymerization and their electrostatic coupling was accomplished using poly(allylamine hydrochloride) as cationic polyelectrolyte linker. Results & conclusion: Colloidal stability of the resulted hybrid nanovectors was demonstrated under physiological conditions together with their fast response and excellent heating efficiency after light stimulation, indicating their potential use as triggered drug-delivery vectors. Moreover, their influence on cell metabolism and cell cycle under subcytotoxic doses were studied showing excellent cytocompatibility.


Nanomaterials ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 161 ◽  
Author(s):  
Debbie K. Ledezma ◽  
Preethi B. Balakrishnan ◽  
Juliana Cano-Mejia ◽  
Elizabeth E. Sweeney ◽  
Melissa Hadley ◽  
...  

In this study, we describe poly (lactic-co-glycolic) acid (PLGA)-based nanoparticles that combine photothermal therapy (PTT) with epigenetic therapy for melanoma. Specifically, we co-encapsulated indocyanine green (ICG), a PTT agent, and Nexturastat A (NextA), an epigenetic drug within PLGA nanoparticles (ICG-NextA-PLGA; INAPs). We hypothesized that combining PTT with epigenetic therapy elicits favorable cytotoxic and immunomodulatory responses that result in improved survival in melanoma-bearing mice. We utilized a nanoemulsion synthesis scheme to co-encapsulate ICG and NextA within stable and monodispersed INAPs. The INAPs exhibited concentration-dependent and near-infrared (NIR) laser power-dependent photothermal heating characteristics, and functioned as effective single-use agents for PTT of melanoma cells in vitro. The INAPs functioned as effective epigenetic therapy agents by inhibiting the expression of pan-histone deacetylase (HDAC) and HDAC6-specific activity in melanoma cells in vitro. When used for both PTT and epigenetic therapy in vitro, the INAPs increased the expression of co-stimulatory molecules and major histocompatibility complex (MHC) Class I in melanoma cells relative to controls. These advantages persisted in vivo in a syngeneic murine model of melanoma, where the combination therapy slowed tumor progression and improved median survival. These findings demonstrate the potential of INAPs as agents of PTT and epigenetic therapy for melanoma.


Sign in / Sign up

Export Citation Format

Share Document