Abstract
Visualization of drug/gene nanocarriers within living tissue is essential for optimization towards clinical applications. In this regard, we have established an intravital real-time confocal laser scanning microscopy (IVRTCLSM) technique with both spatial and temporal resolution for in situ evaluation of nanocarriers. In this chapter, we describe the actual setup of the IVRTCLSM in detail and review several examples analyzing the behavior of nanocarriers. Our new imaging technique can elucidate mechanisms that have not been clarified by conventional methods that require tissue to be disturbed or manipulated ex vivo. IVRTCLSM can thereby ascertain critical barriers residing in a living body and facilitate the development of nanocarriers optimized for drug/gene delivery.
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References
Pack DW, Hoffman AS, Pun S, Stayton PS (2005) Design and development of polymers for gene delivery. Nat Rev Drug Discov 4(7):581–593. doi:10.1038/Nrd1775
Cabral H, Nishiyama N, Kataoka K (2011) Supramolecular nanodevices: from design validation to theranostic nanomedicine. Acc Chem Res 44(10):999–1008. doi:10.1021/ar200094a
Matsumoto Y, Nomoto T, Cabral H, Matsumoto Y, Watanabe S, Christie RJ, Miyata K, Oba M, Ogura T, Yamasaki Y, Nishiyama N, Yamasoba T, Kataoka K (2010) Direct and instantaneous observation of intravenously injected substances using intravital confocal micro-videography. Biomed Opt Express 1(4):1209–1216. doi:10.1364/BOE.1.001209
Nomoto T, Matsumoto Y, Miyata K, Oba M, Fukushima S, Nishiyama N, Yamasoba T, Kataoka K (2011) In situ quantitative monitoring of polyplexes and polyplex micelles in the blood circulation using intravital real-time confocal laser scanning microscopy. J Control Release 151(2):104–109. doi:10.1016/j.jconrel.2011.02.011
Kim HJ, Oba M, Pittella F, Nomoto T, Cabral H, Matsumoto Y, Miyata K, Nishiyama N, Kataoka K (2012) Peg-detachable cationic polyaspartamide derivatives bearing stearoyl moieties for systemic sirna delivery toward subcutaneous bxpc3 pancreatic tumor. J Drug Target 20(1):33–42. doi:10.3109/1061186X.2011.632010
Christie RJ, Miyata K, Matsumoto Y, Nomoto T, Menasco D, Lai TC, Pennisi M, Osada K, Fukushima S, Nishiyama N, Yamasaki Y, Kataoka K (2011) Effect of polymer structure on micelles formed between sirna and cationic block copolymer comprising thiols and amidines. Biomacromolecules 12(9):3174–3185. doi:10.1021/bm2006714
Christie RJ, Matsumoto Y, Miyata K, Nomoto T, Fukushima S, Osada K, Halnaut J, Pittella F, Kim HJ, Nishiyama N, Kataoka K (2012) Targeted polymeric micelles for sirna treatment of experimental cancer by intravenous injection. ACS Nano 6(6):5174–5189. doi:10.1021/nn300942b
Ogris M, Brunner S, Schuller S, Kircheis R, Wagner E (1999) Pegylated DNA/transferrin-pei complexes: reduced interaction with blood components, extended circulation in blood and potential for systemic gene delivery. Gene Ther 6(4):595–605. doi:10.1038/sj.gt.3300900
Akagi D, Oba M, Koyama H, Nishiyama N, Fukushima S, Miyata T, Nagawa H, Kataoka K (2007) Biocompatible micellar nanovectors achieve efficient gene transfer to vascular lesions without cytotoxicity and thrombus formation. Gene Ther 14(13):1029–1038. doi:3302945 [pii] 10.1038/sj.gt.3302945
Kano MR, Bae Y, Iwata C, Morishita Y, Yashiro M, Oka M, Fujii T, Komuro A, Kiyono K, Kaminishi M, Hirakawa K, Ouchi Y, Nishiyama N, Kataoka K, Miyazono K (2007) Improvement of cancer-targeting therapy, using nanocarriers for intractable solid tumors by inhibition of tgf-beta signaling. Proc Natl Acad Sci USA 104(9):3460–3465. doi:0611660104 [pii] 10.1073/pnas.0611660104
Jain RK, Stylianopoulos T (2010) Delivering nanomedicine to solid tumors. Nat Rev Clin Oncol 7(11):653–664. doi:10.1038/nrclinonc.2010.139
Cabral H, Matsumoto Y, Mizuno K, Chen Q, Murakami M, Kimura M, Terada Y, Kano MR, Miyazono K, Uesaka M, Nishiyama N, Kataoka K (2011) Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size. Nat Nanotechnol 6(12):815–823. doi:10.1038/nnano.2011.166
Murakami M, Cabral H, Matsumoto Y, Wu S, Kano MR, Yamori T, Nishiyama N, Kataoka K (2011) Improving drug potency and efficacy by nanocarrier-mediated subcellular targeting. Sci Transl Med 3(64):64ra62. doi:10.1126/scitranslmed.3001385
Haubner R, Gratias R, Diefenbach B, Goodman SL, Jonczyk A, Kessler H (1996) Structural and functional aspects of rgd-containing cyclic pentapeptides as highly potent and selective integrin alpha(v)beta(3) antagonists. J Am Chem Soc 118(32):7461–7472
Kanda T, Sullivan KF, Wahl GM (1998) Histone-gfp fusion protein enables sensitive analysis of chromosome dynamics in living mammalian cells. Curr Biol 8(7):377–385
Acknowledgments
These works were supported by the Core Research Program for Evolutional Science and Technology (CREST) of the Japan Science and Technology Corporation (JST) (K.K.), the Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program) from the Japan Society for the Promotion of Science (JSPS) (K.K.), and Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science, and Technology of Japan (Y.M.).
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Matsumoto, Y. et al. (2013). Intravital Real-Time Confocal Laser Scanning Microscopy for the In Situ Evaluation of Nanocarriers. In: Bae, Y., Mrsny, R., Park, K. (eds) Cancer Targeted Drug Delivery. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7876-8_22
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DOI: https://doi.org/10.1007/978-1-4614-7876-8_22
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