Poster presentation, P145

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

Development and evaluation of antitumor effect of novel NPrCAP-magnetite nanoparticles for chemo-thermo-immunotherapy in malignant melanoma

BACKGROUND: N-Propionyl-4-S-cysteaminylphenol (NPrCAP) is a melanogenesis substrate, specifically taken up by melanoma cells and inhibits their growth by producing cytotoxic free radicals. By taking advantage of this unique chemical agent, we have established melanoma targeting intracellular hyperthermia by conjugating NPrCAP with magnetite nanoparticles (NPrCAP/M) which generate thermal heat upon exposure to alternating magnetic fields (AMF). NPrCAP/M with AMF to B16 melanoma grown in C57BL mice inhibited the growth of not only primary transplant of melanoma cells (chemotherapeutic effect) but also re-challenged, secondary melanoma transplant on to the opposite side of the body (immunotherapeutic effect). This treatment strategy also showed the melanoma necrosis and immune reactions generating cytotoxic T cells with regression of distant skin metastases in human clinical trials. OBJECTIVE: These particles (NPrCAP/PEG/M) were, however, found to be unstable at room temperature and aggregated at the site of subcutaneous administration around/or within melanoma tissues, hence it being necessary to develop a new formula of NPrCAP-magnetite particles that will be stable, and more efficiently and diffusely incorporated into melanoma tissues. APPROACH AND RESULTS: We have successfully made new particles (NPrCAP/PEG/DNM) in which maleimide-PEG5000-Carboxyl-NHS is used to combine NPrCAP and dextran magnetite (DNM). These NPrCAP-magnetite particles are 50~60nm in diameter, much smaller than that of the previous one (350~500 nm), and generate heat efficiently upon exposure to AMF. They did not aggregate around /or within melanoma tissues, and were more diffusely and uniformly distributed. Administration of these new NPrCAP nanoparticles with/or without AMF exposure resulted in marked growth inhibition of primary and secondary melanoma transplants. CONCLUSION: Novel chemo-thermo-immunotherapy to malignant melanoma can be established by employment of the newly developed NPrCAP/PEG/DNM that will be selectively, diffusely and efficiently incorporated into melanoma cells through melanogenesis cascade.

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