Best Practices in Cancer Nanotechnology: Perspective from NCI Nanotechnology Alliance

UNC Eshelman School of Pharmacy, UNC Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, UNC Institute for Pharmacogenomics and Individualized Therapy, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Clinical Cancer Research (Impact Factor: 8.72). 06/2012; 18(12):3229-41. DOI: 10.1158/1078-0432.CCR-11-2938
Source: PubMed


Historically, treatment of patients with cancer using chemotherapeutic agents has been associated with debilitating and systemic toxicities, poor bioavailability, and unfavorable pharmacokinetics. Nanotechnology-based drug delivery systems, on the other hand, can specifically target cancer cells while avoiding their healthy neighbors, avoid rapid clearance from the body, and be administered without toxic solvents. They hold immense potential in addressing all of these issues, which has hampered further development of chemotherapeutics. Furthermore, such drug delivery systems will lead to cancer therapeutic modalities that are not only less toxic to the patient but also significantly more efficacious. In addition to established therapeutic modes of action, nanomaterials are opening up entirely new modalities of cancer therapy, such as photodynamic and hyperthermia treatments. Furthermore, nanoparticle carriers are also capable of addressing several drug delivery problems that could not be effectively solved in the past and include overcoming formulation issues, multidrug-resistance phenomenon, and penetrating cellular barriers that may limit device accessibility to intended targets, such as the blood-brain barrier. The challenges in optimizing design of nanoparticles tailored to specific tumor indications still remain; however, it is clear that nanoscale devices carry a significant promise toward new ways of diagnosing and treating cancer. This review focuses on future prospects of using nanotechnology in cancer applications and discusses practices and methodologies used in the development and translation of nanotechnology-based therapeutics.

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    • "Previous study has indicated that tumor vessels have large endothelial fenestrations ranging in size from 100 to 600 nm [44]. However, the large particle size (>220) will not be able to pass through the fenestrations between the tumor endothelial cells [45] and small particles (<10 nm) are rapidly excreted by the kidney [46]. The size of afatinib/micelles is about 92 nm, which accumulated in tumor tissues. "
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    ABSTRACT: Colorectal cancer (CRC) is known as a common malignant neoplasm worldwide. The role of EGFR/HER2 in CRC is unclear. Afatinib is an irreversible EGFR/HER2 inhibitor. There were few studies of afatinib on CRC. Here, we investigated the protein levels/expressions of HER2 in sera and tumors from CRC patients and the therapeutic effect of afatinib on HER2-overexpressed CRC in vitro and in vivo. The increased HER2 levels were detected in the collected sera and tumors of patients with CRC. The serological HER2 levels were correlated with the tumor HER2 expressions in patients. Afatinib also inhibited the HER2-positive tumor cell growth and caused apoptosis in HER2-overexpressed human colorectal cancer HCT-15 cells but not in low HER2 expressed human gastric cancer MKN45 cells. In vivo study showed that afatinib reduced tumor growth in HER2-overexpressed xenografts. Moreover, afatinib-encapsulated micelles displayed higher cytotoxic activity in HCT-15 cells and were more effective for tumor growth suppression in HCT-15-induced tumor xenografts than afatinib performance alone. Taken together, these findings suggest that higher serum HER2 levels reflect the higher HER2 contents in tumors of CRC patients, and the improved afatinib-encapsulated micelles possess high therapeutic efficacy in HER2-overexpressed CRC in vitro and in vivo.
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    ABSTRACT: We describe the evaluation of doxorubicin-loaded PEG-PE micelles targeting using an ovarian cancer cell spheroid model. Most ovarian cancer patients present at an advanced clinical stage and develop resistance to standard of care platinum/taxane therapy. Doxorubicin is also approved for ovarian cancer but had limited benefits in refractory patients. In this study, we used drug-resistant spheroid cultures of ovarian carcinoma to evaluate the uptake and cytotoxicity of an antibody-targeted doxorubicin formulation. Doxorubicin was encapsulated in polyethylene glycol-phosphatidyl ethanolamine (PEG-PE) conjugated micelles. The doxorubicin-loaded PEG-PE micelles (MDOX) were further decorated with a cancer cell-specific monoclonal 2C5 antibody to obtain doxorubicin-loaded immunomicelles (2C5-MDOX). Targeting and resulting toxicity of doxorubicin-loaded PEG-PE micelles were evaluated in three dimensional cancer cell spheroids. Superior accumulation of 2C5-MDOX compared to free doxorubicin or untargeted MDOX in spheroids was evidenced both by flow cytometry, fluorescence and confocal microscopy. Interestingly, even higher toxicity was measured by lactate dehydrogenase release and terminal deoxynucleotidyl transferase dUTP nick end labeling of targeted doxorubicin micelles in Bcl-2 overexpressing adriamycin-resistant spheroids. Overall, these results support use of spheroids to evaluate tumor targeted drug delivery.
    Journal of Controlled Release 09/2012; 164(1). DOI:10.1016/j.jconrel.2012.09.003 · 7.71 Impact Factor
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    ABSTRACT: Objective: Radiotherapy in oral squamous cell carcinoma (OSCC) could be either through external beam (EBRT) or brachytherapy (BT). In third-world countries, access to novel treatment like BT is limited. This study aimed to compare survival in patients with OSCC treated with EBRT with BT recipients. Methods: We examined cases of nonmetastatic OSCC between January 1, 1987, and December 31, 2007, in the surveillance epidemiology and end results (SEER) registry. A Cox proportional hazards model was used to determine the adjusted relationship between radiation type and survival. Results: There was no significant difference in survival (adjusted) between patients who were treated with BT and those treated with EBRT (P = .330). However, combining EBRT + BT was associated with significantly better survival compared with EBRT alone (hazard ratios [HR] = 0.61, P < .001) or BT alone (HR = 0.70, P = .024). Conclusions: The effect of BT on survival was not significantly different from EBRT.
    09/2012; 115(1). DOI:10.1016/j.oooo.2012.06.023
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