From combinatorial chemistry to cancer targeting nanotherapeutics

Kai Xiao; Juntao Luo; Yuanpei Li; Wenwu Xiao; Joyce S. Lee; Abby M. Gonik; Kit S. Lam

doi:10.1117/12.851931

5 May 2010 From combinatorial chemistry to cancer targeting nanotherapeutics

Kai Xiao, Juntao Luo, Yuanpei Li, Wenwu Xiao, Joyce S. Lee, Abby M. Gonik, Kit S. Lam

Proceedings Volume 7679, Micro- and Nanotechnology Sensors, Systems, and Applications II; 767909 (2010) https://doi.org/10.1117/12.851931
Event: SPIE Defense, Security, and Sensing, 2010, Orlando, Florida, United States

Abstract

We have developed a number of amphiphilic polymers, comprised of a cluster of cholic acids (4 to 10) linked by a series of lysines and attached to one end of a linear polyethylene glycol chain (PEG, 2000-5000 Dalton). Under aqueous condition, such telodendrimers can self-assemble together with hydrophobic payloads to form highly stable micelles (15-150 nm diameter, size tunable). We used near infrared fluorescence (NIRF) optical imaging technique to study the in vivo passive accumulation of our nanocarriers (via EPR effect) in different types and stages of tumors. The results demonstrated that the micelle could preferentially accumulate in many types of tumor xenografts or synografts implanted in mice. Nanoparticle uptake in solid tumors was found to be much higher than that of lymphoma, which could be attributed to the relatively low microvascular density in the latter. We have also demonstrated that micelles smaller than 64 nm preferentially targeted xenografts with high efficiency and with low liver and lung uptake, whereas those micelles at 154 nm targeted the tumor poorly but with very high liver and lung uptake. Telodendrimers decorated with oligolysine or oligoaspartic acid resulted in high uptake of the nanoparticles into the liver. When decorated with cancer targeting ligands identified from the one-bead-one-compound (OBOC) combinatorial library methods, the drug-loaded nanoparticles were rapidly taken up by the target cultured tumor cells causing cell death. In vivo near infra-red optical imaging studies with hydrophobic fluorescent dye demonstrated that xenograft uptake of the micelles was greatly enhanced by the cancer targeting peptide.

Citation Download Citation

Kai Xiao, Juntao Luo, Yuanpei Li, Wenwu Xiao, Joyce S. Lee, Abby M. Gonik, and Kit S. Lam "From combinatorial chemistry to cancer targeting nanotherapeutics", Proc. SPIE 7679, Micro- and Nanotechnology Sensors, Systems, and Applications II, 767909 (5 May 2010); https://doi.org/10.1117/12.851931

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KEYWORDS

Tumors

Nanoparticles

Cancer

Liver

In vivo imaging

Tumor growth modeling

Luminescence

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