Intrinsic,
Cancer Cell-Selective Toxicity of Organic
Photothermal Nanoagent: A Simple Formulation for Combined Photothermal
Chemotherapy of Cancer
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Abstract
Nano-agent-mediated
photothermal therapy (PTT) combined with chemotherapy
has been proposed as an effective strategy against cancer. However,
chemotherapeutic agents often cause serious side effects. Herein,
a novel PTT nanoagent (Cy5.5–MSA–G250) with unanticipated
intrinsic tumor-selective cytotoxicity is developed. The Cy5.5–MSA–G250
nanoparticles (NPs) are created by mixing mouse serum albumin (MSA)
and coomassie brilliant blue (G250) and then conjugated with cyanine
5.5 (Cy5.5). As expected, Cy5.5–MSA–G250 NPs can efficiently
kill cancer cells in vitro and in vivo by PTT. Meanwhile, we accidentally
discover that Cy5.5–MSA–G250 have intrinsic specific
cytotoxicity against tumor cells but not against normal cells. Moreover,
the tumor-specific cytotoxicity of Cy5.5–MSA–G250 is
much stronger than that of cytarabine, an FDA-approved anticancer
drug. In vivo experiments also prove that Cy5.5–MSA–G250
NPs can effectively eliminate residual tumor cells and prevent metastasis.
Further study indicates that selective induction of G1 cell cycle
arrest and inhibition of DNA duplication in tumor cells may be the
possible mechanism of the tumor cell-selective cytotoxicity of Cy5.5–MSA–G250
NPs. In addition, direct visualization, low systematic toxicity, good
biodegradation, and efficient body excretion further make Cy5.5–MSA–G250
NPs attractive for in vivo applications. Taken together, Cy5.5–MSA–G250
NPs are proven to be a promising platform for combined photothermal
chemotherapy