Hepatocellular carcinoma-targeted nanoparticles for cancer therapy

Wu,Chien-Hsun; Lan,Chun-Hsin; Wu,Kuan-Lin; Wu,Yao‑Ming; Jane,Wann-Neng; Hsiao,Michael; Wu,Han-Chung

doi:10.3892/ijo.2017.4205

Hepatocellular carcinoma-targeted nanoparticles for cancer therapy

Authors:
- Chien-Hsun Wu
- Chun-Hsin Lan
- Kuan-Lin Wu
- Yao‑Ming Wu
- Wann-Neng Jane
- Michael Hsiao
- Han-Chung Wu
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Affiliations: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan, R.O.C., Department of Surgery, National Taiwan University Hospital, Taipei 100, Taiwan, R.O.C., Institute of Plant and Microbial Biology, Academia Sinica, Taipei 115, Taiwan, R.O.C., Genomics Research Center, Academia Sinica, Taipei 115, Taiwan, R.O.C.
Published online on: November 16, 2017 https://doi.org/10.3892/ijo.2017.4205
Pages: 389-401
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Nanocarriers, such as liposomes, have the potential to increase the payload of chemotherapeutic drugs while decreasing toxicity to non-target tissues; such advantageous properties can be further enhanced through surface conjugation of nanocarriers with targeting moieties. We previously reported that SP94 peptides, identified by phage display, exhibited higher binding affinity to human hepatocellular carcinoma (HCC) than to hepatocytes and other normal cells. Here, we confirm the tumor-targeting properties of SP94 peptide by near-infrared fluorescence imaging. Non-targeted PEGylated liposomal doxorubicin (LD) and SP94‑conjugated PEGylated liposomal doxorubicin (SP94‑LD) were compared by assessing pharmacokinetics, tissue distribution, and antitumor efficacy in xenograft-bearing mice, in order to investigate the effectiveness of SP94‑mediated targeting for cancer therapy. SP94‑LD demonstrated a significant increase in drug accumulation in tumors, while its plasma residence time was the same as its non-targeted equivalent. Consistent with this result, conjugation of targeting peptide SP94 enhances the therapeutic efficacy of liposomal doxorubicin in mouse models with hepatocellular carcinoma xenografts. Furthermore, combination targeted therapy exhibited a significant enhancement against orthotopic tumor growth, and markedly extended the survival of mice compared with all other treatments. Our study shows that SP94‑mediated targeting enhances antitumor efficacy by improving tumor pharmacokinetics and tissue distribution, allowing large amounts of antitumor drugs to accumulate in tumors.

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