The
specific-targeting approach could promote the specificity of
diagnosis and the accuracy of cancer treatment. The choice of a specific-targeting
receptor is the key step in this approach. Glypican-3 (GPC3) is an
oncofetal proteoglycan anchored on the cell membrane. It is overexpressed
even in the early stage of hepatocellular carcinoma (HCC), whereas
it shows almost no expression in the healthy adult liver. Therefore,
GPC3 may be applied as a specific-targeting receptor for HCC theranostics.
In this study, a GPC3 specific-targeting theranostics nanodevice,
GPC3 targeting peptide (named G12)-modified liposomes co-loaded with
sorafenib (SF) and IR780 iodide (IR780), was developed (GSI-Lip),
which aims to realize early diagnosis and precise chemo-photothermal
therapy of HCC. SF was the first-line chemotherapy drug for the treatment
of HCC. IR780 was used for photothermal therapy and near-infrared
fluorescence imaging. The evaluation of early diagnosis verified that
early-stage tumors (3.45 ± 0.98 mm3, 2 days after
5 × 105 H22 cells’ inoculation in mice) could
be clearly detected using GSI-Lip, which was significantly more sensitive
than folic acid-modified liposomes (p < 0.01,
32.90 ± 10.01 mm3, 4 days after 1 × 106 H22 cells’ inoculation in mice). The study of the endocytic
pathway indicated that specific G12/GPC3 recognition may induce caveolae-mediated
endocytosis of GSI-Lip. Notably, the accumulation of GSI-Lip in tumors
was significantly increased compared with that observed with folic
acid-modified liposomes (p < 0.01). Specific-targeting
endowed the precise antitumor effect of GSI-Lip. GSI-Lip showed a
higher antitumor efficacy in comparison with folic acid-modified liposomes
(inhibition rate: 90.52% vs 84.22%, respectively; p < 0.01). During a period of 21 days, the synergistic chemo-photothermal
therapy (GSI-Lip + laser) exhibited a better antitumor effect versus
GSI-Lip without laser (inhibition rate: 94.93% vs 90.52%, respectively; p < 0.01). Overall, GPC3-targeted GSI-Lip promoted the
sensitivity and specificity of HCC early diagnosis and achieved synergistic
efficacy of chemo-photothermal theranostics, which has potential clinical
applications. Furthermore, the present study revealed that a more
specific-targeting ligand could further improve the efficacy of theranostics
against HCC.
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