Improving proton therapy by metal-containing nanoparticles: nanoscale insights

Schlathölter, Thomas; Eustache, Pierre; Porcel, Erika; Salado, Daniela; Štefančíková, Lenka; Tillement, Olivier; Lux, François; Mowat, Pierre; Biegun, A.; Goethem, Marc-Jan van; Remita, Hynd; Lacombe, S.

doi:10.2147/ijn.s99410

Cited by 54 publications

(77 citation statements)

References 31 publications

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“…When Pt NFs were added to DNA, the radiation effect was strongly amplified. This effect is in agreement with previous studies with Pt NPs coated with PAA and Gadolinium-based nanoparticles activated by photons, protons or heavy ions [15,74,75]. The efficiency of Pt NFs was quantified by calculating the molecular Amplification Factor (mAF):…”

Section: Nanosize Damage Of Pt Nfssupporting

confidence: 87%

A Facile One-Pot Synthesis of Versatile PEGylated Platinum Nanoflowers and Their Application in Radiation Therapy

Yang

Salado-Leza

Porcel

et al. 2020

IJMS

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Nanomedicine has stepped into the spotlight of radiation therapy over the last two decades. Nanoparticles (NPs), especially metallic NPs, can potentiate radiotherapy by specific accumulation into tumors, thus enhancing the efficacy while alleviating the toxicity of radiotherapy. Water radiolysis is a simple, fast and environmentally-friendly method to prepare highly controllable metallic nanoparticles in large scale. In this study, we used this method to prepare biocompatible PEGylated (with Poly(Ethylene Glycol) diamine) platinum nanoflowers (Pt NFs). These nanoagents provide unique surface chemistry, which allows functionalization with various molecules such as fluorescent markers, drugs or radionuclides. The Pt NFs were produced with a controlled aggregation of small Pt subunits through a combination of grafted polymers and radiation-induced polymer cross-linking. Confocal microscopy and fluorescence lifetime imaging microscopy revealed that Pt NFs were localized in the cytoplasm of cervical cancer cells (HeLa) but not in the nucleus. Clonogenic assays revealed that Pt NFs amplify the gamma rays induced killing of HeLa cells with a sensitizing enhancement ratio (SER) of 23%, thus making them promising candidates for future cancer radiation therapy. Furthermore, the efficiency of Pt NFs to induce nanoscopic biomolecular damage by interacting with gamma rays, was evaluated using plasmids as molecular probe. These findings show that the Pt NFs are efficient nano-radio-enhancers. Finally, these NFs could be used to improve not only the performances of radiation therapy treatments but also drug delivery and/or diagnosis when functionalized with various molecules.

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Section: Nanosize Damage Of Pt Nfssupporting

confidence: 87%

A Facile One-Pot Synthesis of Versatile PEGylated Platinum Nanoflowers and Their Application in Radiation Therapy

Yang

Salado-Leza

Porcel

et al. 2020

IJMS

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“…2013; Schlathölter et al. 2016), which have been shown to produce a larger number of Auger electrons when compared to the relatively light elements of biological tissue such as hydrogen, carbon, and oxygen. The increase in the interaction cross section of gold vs. soft tissue decreases at high energies, and it has indeed been found that the energy of the radiation plays a major role in the radiosensitisation effect.…”

Section: Radiotherapy With Gold Nanoparticlesmentioning

confidence: 99%

Gold nanoparticles for cancer radiotherapy: a review

et al. 2016

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Radiotherapy is currently used in around 50% of cancer treatments and relies on the deposition of energy directly into tumour tissue. Although it is generally effective, some of the deposited energy can adversely affect healthy tissue outside the tumour volume, especially in the case of photon radiation (gamma and X-rays). Improved radiotherapy outcomes can be achieved by employing ion beams due to the characteristic energy deposition curve which culminates in a localised, high radiation dose (in form of a Bragg peak). In addition to ion radiotherapy, novel sensitisers, such as nanoparticles, have shown to locally increase the damaging effect of both photon and ion radiation, when both are applied to the tumour area. Amongst the available nanoparticle systems, gold nanoparticles have become particularly popular due to several advantages: biocompatibility, well-established methods for synthesis in a wide range of sizes, and the possibility of coating of their surface with a large number of different molecules to provide partial control of, for example, surface charge or interaction with serum proteins. This gives a full range of options for design parameter combinations, in which the optimal choice is not always clear, partially due to a lack of understanding of many processes that take place upon irradiation of such complicated systems. In this review, we summarise the mechanisms of action of radiation therapy with photons and ions in the presence and absence of nanoparticles, as well as the influence of some of the core and coating design parameters of nanoparticles on their radiosensitisation capabilities.

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“…Recent molecular scale experiments performed with platinum and gadolinium nanoparticles, activated by 150 MeV protons, highlighted the amplification of nanosize bio-damage (Schlathölter et al 2016 ). Here again, the role of hydroxyl radicals was shown.…”

Section: Overview Of Experimental Studiesmentioning

confidence: 99%

Particle therapy and nanomedicine: state of art and research perspectives

2017

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Cancer radiation therapy with charged particle beams, called particle therapy, is a new therapeutic treatment presenting major advantages when compared to conventional radiotherapy. Because ions have specific ballistic properties and a higher biological effectiveness, they are superior to x-rays. Numerous medical centres are starting in the world using mostly protons but also carbon ions as medical beams. Several investigations are attempting to reduce the cost/benefit ratio and enlarge the range of therapeutic indications. A major limitation of particle therapy is the presence of low but significant damage induced in healthy tissues located at the entrance of the ion track prior to reaching the tumour. It is thus a major challenge to improve the targeting of the tumours, concentrating radiation effects in the malignance. A novel strategy, based on the addition of nanoparticles targeting the tumour, was suggested over a decade ago to improve the performance of conventional photon therapy. Recently, similar developments have emerged for particle therapy and the amount of research is now exploding. In this paper, we review the experimental results, as well as theoretical and simulation studies that shed light in the promising outcomes of this strategy and in the underpinning mechanisms. Several experiments provide consistent evidence of significant enhancement of ion radiation effects in the presence of nanoparticles. In view of implementing this strategy for cancer treatment, simulation studies have begun to establish the rationale and the specificity of this effect. In addition, these studies will help to outline a list of possible mechanisms and to predict the impact of ion beams and nanoparticle characteristics. Many questions remain unsolved, but the findings of these first studies are encouraging and open new challenges. After summarizing the main results in the field, we propose a roadmap to pursue future research with the aim to strengthen the potential interplay between particle therapy and nanomedicine.

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Improving proton therapy by metal-containing nanoparticles: nanoscale insights

Cited by 54 publications

References 31 publications

A Facile One-Pot Synthesis of Versatile PEGylated Platinum Nanoflowers and Their Application in Radiation Therapy

A Facile One-Pot Synthesis of Versatile PEGylated Platinum Nanoflowers and Their Application in Radiation Therapy

Gold nanoparticles for cancer radiotherapy: a review

Particle therapy and nanomedicine: state of art and research perspectives

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