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Multifunctional radionanomedicine: a novel nanoplatform for cancer imaging and therapy “...the cutting edge technologies of nanomedicine provide tremendous scope for treating cancer.” Cancer is the second leading cause for death worldwide, highlighting the paramount importance of cancer research. Decades of research has led to many innovative improvements in cancer research, especially in the areas of imaging and therapy [1] . But the fact is that cancer still it remains a chronic and debilitating disease. Despite these concerns, the cutting edge technologies of nanomedicine provide tremendous scope for treating cancer. Recently, the focuses of the emerging nanomedicine field have been to develop multifunctional nanoplatforms that combine both diagnostic/imaging and therapeutic aspects [1–3] . This type of ‘theranostic’ plays a major role for effective cancer imaging and therapy [4,5] . Radiolabeled nanomedicine (nanoparticles) can be termed as ‘radionanomedicine’, which is effective in the treatment of cancer. It can be also used for theranostic purposes with appropriate radionuclides [4,6] . The most important advantage of radionanoparticles is that they do not alter the original characteristics of the entrapped drug molecule/radionuclide. Multifunctional/theranostic radionanomedicines are able to deliver the radionuclide in a targeted manner to cancer cells, to improve the efficacy and safety of both cancer imaging and therapy with the help of a cancertargeting ligand [1] . Indeed, the development of multifunctional/theranostic radionanomedicine is become a possible state-of-the-art in nanomedicine research [5,6] . Liposomes, dendrimers, quantum dots, iron oxide, nanomicelles, perflurocarbon and carbon nanotubes are commonly used carriers for the fabrication of radionanomedicines. The addition of multifunctional/theranostic approaches into these radionanomedicine carriers can make earlier detection and better treatment of cancer possible [7] . Various radionanomedicines have been demonstrated for multifunctional/ theranostic approaches in preclinical animal studies. Clinical and nanotoxicological studies
are required to translate these novel platforms, which have potential clinical benefits for cancer patients [7] . This editorial will focus on recent advances in the design of multifunctional radionanomedicine and its future perspectives.
Current state-of-the-art in multifunctional radionanomedicine research Radiation therapies are commonly used in different cancer treatments to reduce the risk of local recurrence, followed by the surgical removal of the primary tumor. Generally, radionuclide/ radioisotope-loaded nanomedicines are used for internal/systemic radiotherapy. The radioisotopes used in the radionanomedicines for therapy are a‑particle emitters (e.g., 211At and 225Ac), b‑particle emitters (e.g., 90Y, 67Cu, 131I, 186Re and 188 Re) and Auger electron emitters (e.g., 111In and 125 I) [6,7] . These radionanomedicines (radioisotope loaded) containing radioactivity can be useful in the radiotherapy of cancer by passive targeting based on the enhanced permeation and retention effect or active targeting by incorporating a targeting ligand on the surface of the nanoparticle. In addition, some of the radioisotopes are used for imaging, such as g‑particle emitters (e.g., 99mTc and 111In) and b‑particle emitters (e.g., 18F, 64Cu, 86Y and 124I) [7] . Liposomes loaded with radionuclides, ranging from 100 to 800 nm in diameter, are welldeveloped radionanomedicines for cancer imaging and therapy [8,9] . Recently, some liposomal carriers have been designed and evaluated for multifunctional/theranostic properties. For example, Lee and colleagues have evaluated the efficacy of liposomes (nanomedicine) loaded with vinorelbine and 111In (VNI1) on human colorectal adrenocarcinoma using HT‑29/luc mouse xenografts. 111In is an Auger electron radionuclide used as an imaging and therapeutic agent. The distribution of VNI1 in cancer and normal cells was studied. In addition, the
10.2217/NNM.09.107 © 2010 Future Medicine Ltd
Nanomedicine (2010) 5(2), 169–171
Madaswamy S Muthu Author for correspondence: Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India Tel.: + 91 923 519 5928 Fax: + 91 542 236 7568
[email protected]
Barnabas Wilson Department of Pharmaceutics, Dayananda Sagar College of Pharmacy, Kumarasamy Layout, Bangalore, 560078, India
ISSN 1743-5889
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radionanomedicine (VNI1) had imaging/multifunctional capabilities such as g‑scintigraphy, bioluminescence imaging and whole-body autoradiography, which were utilized simultaneously during the evaluation of therapeutic efficacy. 111 In (radionuclide)-loaded liposomes (without vinorelbine) were effective in tumor reduction. In addition, a synergistic effect (addition effect) was observed in groups treated with VNI1 (containing both drug and radionuclide). In this study, authors have demonstrated the multifunctional/ theranostic property of radionanomedicine for effective cancer imaging and therapy [10] .
“A multifunctional/theranostic approach is
one of the important challenges in the area, and will yield much more specific and effective nanoplatforms for cancer imaging and therapy.” Chow and colleagues have explored the multifunctional/theranostic approach of a radionanomedicine in an animal model of colorectal cancer [11] . This attempt was made to reduce the uptake of radiotracer by the reticuloendothelial system using 6% polyethylene glycol rather than 0.9% polyethylene glycol in the previous report [10] . The radionanomedicines (nanoliposomes of 100 nm) loaded with vinorelbine and 111In (VNI2) were evaluated simultaneously for therapeutic effect (on HT‑29/ luc mouse xenografts) and imaging, such as g‑scintigraphy, bioluminescence imaging and whole-body autoradiography. The detailed preclinical study showed the multifunctional/theranostic approach of radionanomedicine with synergistic effect, which combine the action of 111In with vinorelbine (anticancer drug). The safety and feasibility (toxicology) of the radionanomedicine were also demonstrated by animal body weights, histopathology and biochemistry/hematology analysis after VNI2 administration [11] . In another study, DeNardo and colleagues evaluated both multifunctional and cancertargeting concepts by designing 111In‑chimeric L6 monoclonal antibody-linked iron oxide nanoparticles (targeted multifunctional radionanomedicines). The pharmacokinetics, tumor uptake and therapeutic effect of inductively heating these radionanoparticles by externally applied alternating magnetic field were studied in athymic mice bearing human breast cancer HBT 3477 xenografts. The study demonstrates the design of new and safer modality for cancer imaging and therapy [12] . These novel ideas can 170
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be utilized during the development of different targeted/nontargeted multifunctional radionanomedicine (e.g., dendrimers, quantum dots etc) by incorporating anticancer drug, targeting ligand and radionuclide.
Future perspective Radionanomedicines are facing many future challenges such as multireceptor tumor targeting, radionuclide encapsulation, multimodality imaging, multiple drug loading, nanotoxicology and pharmaceutical regulations, including stability testing [5,13] . The emerging radionanomedicines lie in multifunctional/theranostic platforms [4] . The future development of multifunctional radionanomedicine should cover efficient and specific delivery of therapeutic agents (e.g., radionuclide, anticancer drugs), including imaging function devoid of any systemic adverse effects. A multidisciplinary approach to the development of radionanomedicine will bring valuable clinical benefits to the imaging and therapy of cancer. Conclusion Multifunctional radionanomedicines in this editorial are defined as radionuclide (incorporated for both imaging and therapy e.g., 111 In)-encapsulated nanocarriers, which are the novel products of a multidisciplinary approach. Recent research on radionanomedicines has shown their efficacy and safety. However, issues to be addressed before exploiting the clinical benefits of radionanomedicines include radionuclide stability in the nanomedicines, practical control over radionuclide during its fabrication, radionuclide leakage from nanomedicines, especially in liposomes and nanomicelles, which leads to possible toxicities, scale-up and possible interaction between the drug and radionuclide. A multifunctional/ theranostic approach is one of the important challenges in the area, and will yield much more specific and effective nanoplatforms for cancer imaging and therapy. Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript. future science group
Multifunctional radionanomedicine: a novel nanoplatform for cancer imaging & therapy
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