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Octreotide-Modified Polymeric Micelles as Potential Carriers for Targeted Docetaxel Delivery to Somatostatin Receptor Overexpressing Tumor Cells

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ABSTRACT

Purpose

Somatostatin analogue octreotide (OCT)-modified PEG-b-PLA micelles were constructed to bind to somatostatin receptors (SSTRs) overexpressed on tumor cells for enhanced intracellular drug delivery and improved therapeutic efficacy for malignant tumors.

Methods

Copolymers conjugated with octreotide (OCT-PEG6000-b-PLA5000) were synthesized. The fluorescent probe DiI or docetaxel (DTX)-loaded micelles with or without octreotide modification (OCT-PM-DiI, PM-DiI, OCT-PM-DTX and PM-DTX) were prepared, and their physiochemical properties, intracellular delivery in vitro or anti-tumor activity in vivo were evaluated, respectively.

Results

The CMC of OCT-PEG6000-b-PLA5000 was quite low (<10−6 mol/L). All micelles were less than 80 nm with spherical shape and high encapsulation efficiency. DTX molecules were well dispersed in the micelles without chemical interactions with the polymers. Flow cytometry and confocal microscopy results showed that OCT-PM-DiI enhanced intracellular delivery efficiency via receptor-mediated endocytosis in NCI-H446 cells; the optimal modification ratio of OCT on micelle surface was 5%. OCT-PM-DTX exhibited higher retardation of tumor growth after intravenous injections into xenograft NCI-H446 tumor model; octreotide-modified micelles did not show severe toxicity.

Conclusions

SSTRs targeting micelles may serve as promising nanocarriers in tumor treatment for hydrophobic anticancer drugs, such as DTX.

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ACKNOWLEDGMENTS

This study was supported by projects from Ministry of Science and Technology, PR China (No. 2009CB930300, No. 2007AA021811, No. 2009ZX09310-001). We thank Dr. Jinfeng Du for his help in preparing the graphs of the manuscript.

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Authors and Affiliations

  1. State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing, 100191, People’s Republic of China

    Yuan Zhang, Xueqing Wang, Jiancheng Wang, Xuan Zhang & Qiang Zhang

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  1. Yuan Zhang
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  2. Xueqing Wang
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  3. Jiancheng Wang
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  4. Xuan Zhang
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  5. Qiang Zhang
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Correspondence to Yuan Zhang or Qiang Zhang.

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Zhang, Y., Wang, X., Wang, J. et al. Octreotide-Modified Polymeric Micelles as Potential Carriers for Targeted Docetaxel Delivery to Somatostatin Receptor Overexpressing Tumor Cells. Pharm Res 28, 1167–1178 (2011). https://doi.org/10.1007/s11095-011-0381-1

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  • DOI: https://doi.org/10.1007/s11095-011-0381-1

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