Hepatocellular carcinoma-targeted nanoparticles for cancer therapy
Journal
International journal of oncology
Journal Volume
52
Journal Issue
2
Pages
389
Date Issued
2018-02
Author(s)
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.
Subjects
hepatocellular carcinoma; drug delivery system; pharma-cokinetics; biodistribution; ligand-targeted therapeutics
SDGs
Other Subjects
doxorubicin; nanoparticle; vinorelbine tartrate; antineoplastic agent; drug carrier; liposome; peptide; animal experiment; animal model; animal tissue; Article; cancer survival; cancer therapy; controlled study; drug accumulation; drug distribution; drug dosage form comparison; drug efficacy; drug formulation; encapsulation; liver cell carcinoma; mean residence time; mouse; near infrared spectroscopy; nonhuman; outcome assessment; priority journal; survival analysis; tumor xenograft; animal; drug screening; human; liver cell carcinoma; liver tumor; molecularly targeted therapy; procedures; SCID mouse; Animals; Antineoplastic Agents; Carcinoma, Hepatocellular; Drug Carriers; Humans; Liposomes; Liver Neoplasms; Mice; Mice, SCID; Molecular Targeted Therapy; Nanoparticles; Peptides; Xenograft Model Antitumor Assays
Publisher
SPANDIDOS PUBL LTD
Type
journal article