Chemorad Nanoparticles: A Novel Multifunctional Nanoparticle Platform for Targeted Delivery of Concurrent Chemoradiation

Abstract

Aim-The development of chemoradiation -the concurrent administration of chemotherapy and radiotherapy -has led to significant improvements in local tumor control and survival. However, it is limited by its high toxicity. In this study, we report the development of a novel NP (nanoparticle) therapeutic, ChemoRad NP, which can deliver biologically targeted chemoradiation.Method-A biodegradable and biocompatible lipid-polymer hybrid NP that is capable of delivering both chemotherapy and radiotherapy was formulated. 111 and yttrium 90 as model drugs, we demonstrated that the ChemoRad NP can encapsulate chemotherapeutics (up to 9% of NP weight) and radiotherapeutics (100 mCi of radioisotope per gram of NP) efficiently and deliver both effectively. Using prostate cancer as a disease model, we demonstrated the targeted delivery of ChemoRad NPs and the higher therapeutic efficacy of ChemoRad NPs. Results-Using docetaxel, indium Conclusion-We Financial & competing interests disclosureThe authors have no other 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 apart from those disclosed. No writing assistance was utilized in the production of this manuscript. NIH Public AccessAuthor Manuscript Nanomedicine (Lond). Author manuscript; available in PMC 2011 February 1. Published in final edited form as:Nanomedicine (Lond). 2010 April ; 5(3): 361-368. doi:10.2217/nnm.10.6. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptThe advent of concurrent administration of chemotherapy and radiotherapy (chemoradiation) has significantly improved cancer care. Currently, it is the standard of treatment for many cancers, including esophageal, gastric, head and neck, and rectal cancers [1]. However, chemoradiation is limited by its higher (potentially life-threatening) toxicity, thereby precluding patients with poor general health from undergoing treatment. One potential strategy to improve chemoradiation utilizes advancements in drug delivery technology to improve efficacy and lower toxicity of the treatment. In particular, advances in nanotechnology have led to the development of nanoparticle (NP) drug-delivery vehicles, which can potentially improve the codelivery of chemoradiation. NPs are particularly well suited for cancer applications as they passively accumulate in tumors through the enhanced permeability and retention effect [2]. The proof-of-principle was observed in liposomal formulations of chemotherapeutics, such as Doxil, which demonstrated lower toxicity than their small molecular counterparts [3]. Our group and other investigators have demonstrated that the combination of biological targeting and NP delivery result in a higher concentration of chemotherapeutics within cancer cells [4][5][6][7][8][9][10][11][12]. Considering the many favorable characteristics of targeted NPs, we became interested in developing a targeted NP platform that is capable ...

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“…13 These nanoparticles can encapsulate chemotherapeutics up to 9% of the nanoparticle weight and radiotherapeutics of 100 mCi of radioisotope per gram. 13 Cisplatin (CDDP)-loaded magnetic nanoparticles (MNP) in combination with chemoradiotherapy showed that CDDP-loaded MNP alone or in combination with radiotherapy can effectively inhibit the growth of nasopharyngeal carcinoma in nude mice without increasing the toxicity. 14 Ho emits 81-keV γ-rays (6.6% photon yield), which can be used to quantify and image the biodistribution of the particles.…”

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