Cisplatin(DDP) is a platinum-based chemotherapy drug which was widely used to treat various types of cancer including Head and Neck Squamous Cell Carcinoma (HNSCC). However, very little DDP reaches the tumor tissue due to poor specificity and it induces dose-limiting toxicities. The delivery of DDP selectively into a tumor mass has the potential to minimize toxicity to normal tissues and to improve the antitumor efficiency. We have developed novel nanoparticles by conjugating folic acid to modified heparin, then loaded cisplatin (DDP) into the targeted nanoparticles via the exchange of reaction of Pt from the chloride to the carboxylates on the nanoparticles. Uptake and biodistribution of DDP delivered by the nanoparticles or the free DDP form in vitro and in vivo was quantified by inductively coupled plasma-mass spectrometry (ICP-MS). We showed that DDP-Heparin-Folic Acid (FA) Nanoparticles are specifically internalized by FR-expressing HNSCC KB cells in vitro (17 fold higher than free DDP). Systemic delivery of DDP-Heparin-FA nanoparticles (2.5 mg/kg; 4 times treatment at 3 days intervals) into nude mice bearing KB cell tumors (6 mice/group) lead to selective accumulation of the DDP in subcutaneous tumor lesions (74 ppb/mg tissue for HFDDP, 16.5 ppb/mg tissue for DDP, P<0.05), and have significant antitumor activity. Furthermore, mice receiving DDP-Heparin-FA nanoparticles showed no significant body weight loss or damage to liver or spleen, whereas mice that received free DDP had significant weight loss and massive organ damage. Our results suggest that DDP-Heparin-FA nanoparticles have the potential to be used for delivery of this highly toxic chemotherapeutic agent with reduced side effects in HNSCC. (This research was supported by the National Cancer Institute award 5 P50 CA128613) 
Cisplatin(DDP) is a platinum-based chemotherapy drug which was widely used to treat various types of cancer including Head and Neck Squamous Cell Carcinoma (HNSCC). However, very little DDP reaches the tumor tissue due to poor specificity and it induces dose-limiting toxicities. The delivery of DDP selectively into a tumor mass has the potential to minimize toxicity to normal tissues and to improve the antitumor efficiency. We have developed novel nanoparticles by conjugating folic acid to modified heparin, then loaded cisplatin (DDP) into the targeted nanoparticles via the exchange of reaction of Pt from the chloride to the carboxylates on the nanoparticles. Uptake and biodistribution of DDP delivered by the nanoparticles or the free DDP form in vitro and in vivo was quantified by inductively coupled plasma-mass spectrometry (ICP-MS). We showed that DDP-Heparin-Folic Acid (FA) Nanoparticles are specifically internalized by FR-expressing HNSCC KB cells in vitro (17 fold higher than free DDP). Systemic delivery of DDP-Heparin-FA nanoparticles (2.5 mg/kg; 4 times treatment at 3 days intervals) into nude mice bearing KB cell tumors (6 mice/group) lead to selective accumulation of the DDP in subcutaneous tumor lesions (74 ppb/mg tissue for HFDDP, 16.5 ppb/mg tissue for DDP, P<0.05), and have significant antitumor activity. Furthermore, mice receiving DDP-Heparin-FA nanoparticles showed no significant body weight loss or damage to liver or spleen, whereas mice that received free DDP had significant weight loss and massive organ damage. Our results suggest that DDP-Heparin-FA nanoparticles have the potential to be used for delivery of this highly toxic chemotherapeutic agent with reduced side effects in HNSCC. (This research was supported by the National Cancer Institute award 5 P50 CA128613) 

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3678.