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Systemic co-delivery of doxorubicin and siRNA using nanoparticles conjugated with EGFR-specific targeting peptide to enhance chemotherapy in ovarian tumor bearing mice

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Abstract

This aim of this study was to develop peptide-conjugated nanoparticles (NPs) for systemic co-delivery of siRNA and doxorubicin to enhance chemotherapy in epidermal growth factor receptor (EGFR) high-expressed ovarian tumor bearing mice. The active targeting NPs were prepared using heptapeptide-conjugated poly(d,l-lactic-co-glycolic acid)–poly(ethylene glycol). The particle sizes of peptide-free and peptide-conjugated NPs were 159.3 ± 32.5 and 184.0 ± 52.9 nm, respectively, with zeta potential −21.3 ± 3.8 and −15.3 ± 2.8 mV. The peptide-conjugated NPs uptake were more efficient in EGFR high-expressed SKOV3 cells than in EGFR low-expressed HepG2 cells due to heptapeptide specificity. The NPs were used to deliver small molecule anticancer drug (e.g., doxorubicin) and large molecule genetic agent (e.g., siRNA). The IC50 of doxorubicin-loaded peptide-conjugated NPs (0.09 ± 0.06 μM) was significantly lower than peptide-free NPs (5.72 ± 2.64 μM). The similar result was observed in siRNA-loaded NPs. The peptide-conjugated NPs not only served as a nanocarrier to efficiently deliver doxorubicin and siRNA to EGFR high-expressed ovarian cancer cells but also increased the intracellular accumulation of the therapeutic agents to induce assured anti-tumor growth effect in vivo.

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Acknowledgments

This work was supported by National Science Council in Taiwan. The authors thank Dr. Fu Hsiung Chang for the Zetasizer and Dr. Hui-Lin Wu for HepG2 cell line.

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Authors and Affiliations

  1. Graduate Institute of Pharmaceutical Sciences, School of Pharmacy, National Taiwan University, F 12 No. 1 Jen Ai Rd., Sec. 1, Taipei, 100, Taiwan

    C. W. Liu & W. J. Lin

  2. Pharmaceutical Optimization Technology Division, Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, 30011, Taiwan

    C. W. Liu

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  1. C. W. Liu
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  2. W. J. Lin
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Correspondence to W. J. Lin.

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Liu, C.W., Lin, W.J. Systemic co-delivery of doxorubicin and siRNA using nanoparticles conjugated with EGFR-specific targeting peptide to enhance chemotherapy in ovarian tumor bearing mice. J Nanopart Res 15, 1956 (2013). https://doi.org/10.1007/s11051-013-1956-z

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  • DOI: https://doi.org/10.1007/s11051-013-1956-z

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