In-vivo tumor targeting of pluronic-based nano-carriers.
Pluronic-based nano-carriers including bare forms that were composed of Pluronic F 68(NC(PF 68)) or Pluronic F 127(NC(PF 127)), and chitosan-conjugated forms (Chito-NC(PF 68) or Chito-NC(PF 127)) were prepared by photo-polymerizing two kinds of diacrylated Pluronic (F 68 and F 127) and acrylated chitosan to investigate the effect of chitosan conjugation and their physicochemical characteristics (size and hydrophilicity) of Pluronic-based nano-carriers on the tumor targeting efficiency. All of the nano-carriers were stable in serum-containing media without forming any aggregation and did not show any acute cytotoxicity to both normal (NIH3T3 fibroblast) and tumor (SCC7) cells. Chitosan conjugation did not change their sizes or thermo-sensitive properties of the nano-carriers, but significantly increased their in-vitro cellular uptake compared to the corresponding bare forms. The in-vivo tumor accumulation of these nano-carriers was optically monitored by using Cy5.5-attached nano-carriers in SCC7 tumor-bearing mice. For all cases, local accumulation of the injected nano-carriers in liver was not dominant compared to the tumor site, demonstrating good tumor targeting efficacy of the Pluronic-based nano-carriers. Among different samples, chitosan-conjugated nano-carriers showed much better tumor accumulation than bare forms, and mostly remained up to 72h, implying prolonged blood circulation and more efficient tumor accumulation. Between Chito-NC(PF 68) and Chito-NC(PF 127), Chito-NC(PF 68) showed a little better tumor accumulation and retention, suggesting the difference in Pluronic, thus difference in hydrophilicity and the size of the nano-carriers also might affect the tumor targeting. In contrast, bare nano-carriers were initially accumulated well in tumor, but they were excreted from the tumor site relatively rapidly. Therefore, chitosan-functionalization was very effective for improving the tumor targeting efficacy of Pluronic-based nano-carriers.
Kim
Ja-Young
JY
Department of Materials Science and Engineering and Department of Nanobio Materials and Electronics, Gwangju Institute of Science and Technology, 261 Cheomdan-gwagiro, Buk-gu, Gwangju 500-712, Korea.
Choi
Won Il
WI
Kim
Young Ha
YH
Tae
Giyoong
G
Lee
Seung-Young
SY
Kim
Kwangmeyung
K
Kwon
Ick Chan
IC
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics; D004339:Drug Compounding; D004355:Drug Stability; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry*; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism; D020442:Poloxamer / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D004337:Drug Carriers; D020442:Poloxamer; D048271:Chitosan