Synthetic nanoparticles for delivery of radioisotopes and radiosensitizers in cancer therapy

Zhao, Jun; Zhou, Min; Li, Chun

doi:10.1186/s12645-016-0022-9

Cited by 53 publications

(27 citation statements)

References 146 publications

(184 reference statements)

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“…An interesting concept toward radiolabeled nanoparticles is to presynthesize the nonradioactive variant and then use particle beam or reactor-based activation to transmute an atom in situ (Fig. 3) (5). Both neutron (61,62) and proton (63,64) activations have been reported to produce radiolabeled nanoparticles via 18 O(p,n) 18 F, 16 O(p,a) 13 N, and 165 Ho(n,g) 166 Ho transmutation.…”

Section: Particle Beam or Reactor Activationmentioning

confidence: 99%

Advanced Methods for Radiolabeling Multimodality Nanomedicines for SPECT/MRI and PET/MRI

Lamb

Holland

2017

J Nucl Med

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The advent of hybrid cameras that combine MRI with either SPECT or PET has stimulated growing interest in developing multimodality imaging probes. Countless options are available for fusing magnetically active species with positron- or γ-ray-emitting radionuclides. The initial problem is one of choice: which chemical systems are a suitable basis for developing hybrid imaging agents? Any attempt to answer this question must also address how the physical, chemical, and biologic properties of a unified imaging agent can be tailored to ensure that optimum specificity and contrast are achieved simultaneously for both imaging modalities. Nanoparticles have emerged as attractive platforms for building multimodality radiotracers for SPECT/MRI and PET/MRI. A wide variety of nanoparticle constructs have been utilized as radiotracers, but irrespective of the particle class, radiolabeling remains a key step. Classic methods for radiolabeling nanoparticles involve functionalization of the particle surface, core, or coating. These modifications typically rely on using traditional metal ion chelate or prosthetic group chemistries. Though seemingly innocuous, appending nanoparticles with these radiolabeling handles can have dramatic effects on important properties such as particle size, charge, and solubility. In turn, alterations in the chemical and physical properties of the nanoparticle often have a negative impact on their pharmacologic profile. A central challenge in radiolabeling nanoparticles is to identify alternative chemical methods that facilitate the introduction of a radioactive nuclide without detrimental effects on the pharmacokinetic and toxicologic properties of the construct. Efforts to solve this challenge have generated a range of innovative chelate-free radiolabeling methods that exploit intrinsic chemical features of nanoparticles. Here, the chemistry of 9 mechanistically distinct methods for radiolabeling nanoparticles is presented. This discourse illustrates the evolution of nanoparticle radiochemistry from classic approaches to modern chelate-free or intrinsic methods.

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Section: Particle Beam or Reactor Activationmentioning

confidence: 99%

Advanced Methods for Radiolabeling Multimodality Nanomedicines for SPECT/MRI and PET/MRI

Lamb

Holland

2017

J Nucl Med

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“…[7,23] During RT, nanomaterials can play a key role in tumor treatment by acting either as therapeutic agents by themselves, or as delivery carriers for other therapeutic units. [9,25] The combination of nanomedicine-based chemotherapy may also be combined with RT to achieve synergistic anti-tumor therapeutic outcomes. [24] Nanomaterials can be chemically modified for active tumor targeting as multifunctional nano-carriers to deliver therapeutic radioisotopes for radioisotope therapy.…”

Section: Introductionmentioning

confidence: 99%

Emerging Nanotechnology and Advanced Materials for Cancer Radiation Therapy

et al. 2017

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Radiation therapy (RT) including external beam radiotherapy (EBRT) and internal radioisotope therapy (RIT) has been widely used for clinical cancer treatment. However, owing to the low radiation absorption of tumors, high doses of ionizing radiations are often needed during RT, leading to severe damages to normal tissues adjacent to tumors. Meanwhile, the RT efficacies are limited by different mechanisms, among which the tumor hypoxia-associated radiation resistance is a well-known one, as there exists hypoxia inside most solid tumors while oxygen is essential to enhance radiation-induced DNA damages. With the development in nanotechnology, there have been great interests in using nanomedicine strategies to enhance radiation responses of tumors. Nanomaterials containing high-Z elements to absorb radiation rays (e.g. X-ray) can act as radio-sensitizers to deposit radiation energy within tumors and promote treatment efficacy. Nanoscale carriers are able to deliver therapeutic radioisotopes into tumors for internal RIT, or chemotherapeutic drugs for synergistically combined chemo-radiotherapy. As uncovered in recent studies, the tumor microenvironment could be modulated by various nanomedicine approaches to overcome hypoxia-associated radiation resistance. Herein, the authors will summarize the applications of nanomedicine for RT cancer treatment, and pay particular attention to the latest development of 'advanced materials' for enhanced cancer RT.

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“…Nanotechnology has great potential in the development of medical diagnosis and therapy by designing and synthesizing a wide range of nanomaterials for applications in targeted drug delivery, accurate diagnosis, and treatment of diseases such as cancers [1]. Until now, various of nanoparticles (NPs) have been utilized as radioisotope carriers in radionuclide therapy, among them organic NPs such as polymeric matrixes [2], liposomes [3] and inorganic NPs such as gold [4], metal oxides [5] and insoluble salts of metals [6]. The advantage of NPs is their ability to "carry" many radioactive atoms within a single carrier.…”

Section: Introductionmentioning

confidence: 99%

Trastuzumab Conjugated Superparamagnetic Iron Oxide Nanoparticles Labeled with 225Ac as a Perspective Tool for Combined α-Radioimmunotherapy and Magnetic Hyperthermia of HER2-Positive Breast Cancer

et al. 2020

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It has been proven and confirmed in numerous repeated tests, that the use of a combination of several therapeutic methods gives much better treatment results than in the case of separate therapies. Particularly promising is the combination of ionizing radiation and magnetic hyperthermia in one drug. To achieve this objective, magnetite nanoparticles have been modified in their core with α emitter 225Ac, in an amount affecting only slightly their magnetic properties. By 3-phosphonopropionic acid (CEPA) linker nanoparticles were conjugated covalently with trastuzumab (Herceptin®), a monoclonal antibody that recognizes ovarian and breast cancer cells overexpressing the HER2 receptors. The synthesized bioconjugates were characterized by transmission electron microscopy (TEM), Dynamic Light Scattering (DLS) measurement, thermogravimetric analysis (TGA) and application of 131I-labeled trastuzumab for quantification of the bound biomolecule. The obtained results show that one 225Ac@Fe3O4-CEPA-trastuzumab bioconjugate contains an average of 8–11 molecules of trastuzumab. The labeled nanoparticles almost quantitatively retain 225Ac (>98%) in phosphate-buffered saline (PBS) and physiological salt, and more than 90% of 221Fr and 213Bi over 10 days. In human serum after 10 days, the fraction of 225Ac released from 225Ac@Fe3O4 was still less than 2%, but the retention of 221Fr and 213Bi decreased to 70%. The synthesized 225Ac@Fe3O4-CEPA-trastuzumab bioconjugates have shown a high cytotoxic effect toward SKOV-3 ovarian cancer cells expressing HER2 receptor in-vitro. The in-vivo studies indicate that this bioconjugate exhibits properties suitable for the treatment of cancer cells by intratumoral or post-resection injection. The intravenous injection of the 225Ac@Fe3O4-CEPA-trastuzumab radiobioconjugate is excluded due to its high accumulation in the liver, lungs and spleen. Additionally, the high value of a specific absorption rate (SAR) allows its use in a new very perspective combination of α radionuclide therapy with magnetic hyperthermia.

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Synthetic nanoparticles for delivery of radioisotopes and radiosensitizers in cancer therapy

Cited by 53 publications

References 146 publications

Advanced Methods for Radiolabeling Multimodality Nanomedicines for SPECT/MRI and PET/MRI

Advanced Methods for Radiolabeling Multimodality Nanomedicines for SPECT/MRI and PET/MRI

Emerging Nanotechnology and Advanced Materials for Cancer Radiation Therapy

Trastuzumab Conjugated Superparamagnetic Iron Oxide Nanoparticles Labeled with 225Ac as a Perspective Tool for Combined α-Radioimmunotherapy and Magnetic Hyperthermia of HER2-Positive Breast Cancer

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