Synergistically enhanced anticancer effect of codelivered curcumin and siPlk1 by stimuli-responsive α-lactalbumin nanospheres

Nanomedicine
Dan LiYuan Li

Abstract

To achieve enhanced anticancer efficacy by combined siPlk1 and curcumin (cur) therapy using α-lactalbumin (α-lac) nanocarrier delivery. α-Lac was partially hydrolyzed into amphiphilic peptides, and then self-assembled into nanospheres (NS). Cur was loaded into their hydrophobic core during the self-assembly process. siPlk1-SH was cross-linked with the endogenous cysteines on the NS. CRGDK peptide was conjugated on NS to target integrins overexpressed in HeLa cells. The Cur and siPlk1 coloaded NS formulations possessed an enhanced tumor targeting and antitumor properties. Drugs were responsively released from disulfide bonds cross-linked RGD-NS/Cur/siPlk1 corresponding to the high intracellular glutathione concentrations of cancer cells. Both in vitro cell viability experiments and in vivo antitumor evaluations demonstrated that the codelivered nanosphere platform exhibited excellent tumor targeting and synergistic antitumor efficacy.

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Methods Mentioned

BETA
transmission electron microscopy
dynamic light scattering
electrophoresis
flow cytometry
optical microscopy
PCR
transfection
Protein Assay
xenograft
gene knockdown

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