Abstract
Combinational therapy is usually considered as a preferable approach for effective cancer therapy. Especially, combinational chemotherapies targeting different molecular targets are of particular interest due to its high flexibility as well as efficiency. In our study, the surface of silica nanoparticles (SLN) was modified with low-density lipoprotein (LDL) to construct platform (LDL-SLN) capable of specifically targeting low-density lipoprotein receptors (LDLRs) that overexpressing in hepatocellular carcinoma (HCC). In addition, the versatile drug loading capacity of LDL-SLN was employed to fabricate a preferable drug delivery system to co-deliver sorafenib (Sor) and doxorubicin (Dox) for combinational chemotherapy of HCC. Our results revealed that the LDL-SLN/Sor/Dox nanoparticles with size around 100 nm showed preferable stability in physiological environments. Moreover, the LDL-SLN/Sor/Dox could target LDLR overexpressed HepG2 cells. More importantly, both in vitro and in vivo experiments demonstrated that the LDL-SLN/Sor/Dox exerted elevated antitumor efficacy compared to Sor or Dox alone, which indicated that LDL-SLN/Sor/Dox could be a powerful tool for effective combinational chemotherapy of HCC.
Highlights
Combinational chemotherapy is generally recognized as a preferable approach for cancer therapy due to its superiority in overcoming drug resistance and heterogeneity of cancer cells (Sui et al, 2017; Li et al, 2018)
Amine decorated silica nanoparticles (SLN) have widely adopted as a powerful tool to construct multifunctional drug delivery systems (DDS) due to the existence of excess primary amine groups on the surface that further modification of other functional groups could be achieved
The results revealed that SLN/Sor/ Dox was composed of nano-sized particles with a diameter of around 90.6 nm and a relatively small PDI of 0.193
Summary
Combinational chemotherapy is generally recognized as a preferable approach for cancer therapy due to its superiority in overcoming drug resistance and heterogeneity of cancer cells (Sui et al, 2017; Li et al, 2018). It is usually achieved by simultaneously delivering different chemotherapeutics with different pharmacological action mechanisms to the same target cell (Liu et al, 2017; Yan et al, 2017). Clinical observations reveal that Sor displays only cytostatic effects rather than cytotoxicity, which results in the disappointing fact that other compensatory oncogenic pathways were activated to facilitate the cancer cells to evade pharmacotherapy (Thapa et al, 2016; Thomas & Balthasar, 2016). Sor should be used along with other cytotoxic drugs to achieve better chemotherapy effects
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