Low density lipoprotein modified silica nanoparticles loaded with docetaxel and thalidomide for effective chemotherapy of liver cancer

Abstract

In the present study, we successfully developed a docetaxel (DTX) and thalidomide (TDD) co-delivery system based on low density lipoprotein (LDL) modified silica nanoparticles (LDL/SLN/DTX/TDD). By employing the tumor homing property of LDL and the drug-loading capability of silica nanoparticles, the prepared LDL/SLN/DTX/TDD was expected to locate and specifically deliver the loaded drugs (DTX and TDD) to achieve effective chemotherapy of liver cancer. In vitro analysis revealed that nano-sized LDL/SLN/DTX/TDD with decent drug loading capabilities was able to increase the delivery efficiency by targeting the low density lipoprotein receptors, which were overexpressed on HepG2 human hepatocellular liver carcinoma cell line, which exerted better cytotoxicity than unmodified silica nanoparticles and free drugs. In vivo imaging and anti-cancer assays also confirmed the preferable tumor-homing and synergetic anti-cancer effects of LDL/SLN/DTX/TDD.

<p>Nanocarrier-Based Therapeutics and Theranostics Drug Delivery Systems for Next Generation of Liver Cancer Nanodrug Modalities</p>

“…summarised various inorganic nanocarriers for the application of liver cancer nano drug delivery. For example, Ao et al, 2018 studied lipoprotein modified silica nanoparticles loaded with Docetaxel and Thalidomide to observe the cytotoxicity of HepG2 human hepatocellular liver carcinoma cell line and found effective tumor killing on liver cancer 37. …”

Low-density lipoprotein decorated silica nanoparticles co-delivering sorafenib and doxorubicin for effective treatment of hepatocellular carcinoma

“…Amine-modified SLN was firstly synthesized in a water-in-oil microemulsion with minor modification as previously reported (Wu et al., 2015). Later, the as prepared amine-modified SLN was subjected to drug loading (Ao et al., 2018). In brief, SLN was resuspended in mixed solution (ethanol:pyridine =1:1, v / v ) and incubated with Sor and Dox (5 mg/mL) for 30 min.…”

“…In recent years, nanoscale drug delivery systems (DDS), especially inorganic ones, have been designed with the purpose to encapsulate both drugs into one vector with desired ratios and specifically deliver the cargos to neoplastic tissues (Baeza et al., 2017; Wu et al., 2017; Tang et al., 2018). Inorganic materials including gold nanoparticles and silica nanoparticles (SLNs), have attracted the interests of many researchers (Rizwan et al., 2017; Ao et al., 2018). The introduction of SLNs for biomedical application is a milestone in cancer therapy, since the versatile capabilities of SLNs, including high biocompatibility and facile surface modification, have made it a superior carrier to other counterparts (Song et al., 2016).…”

Nanotechnology as a Platform for the Development of Injectable Parenteral Formulations: A Comprehensive Review of the Know-Hows and State of the Art

“…Ligands used for targeting purposes need to have substantially high affinity and specificity for the receptor of interest, and relatively simple conjugation chemistry. For instance, abundant expression of transferrin receptors [ 364 ], folate receptors [ 365 ], lactoferrin receptors [ 366 ], low-density lipoprotein (LDL) receptors [ 367 ], interleukin receptors [ 368 ], somatostatin receptors [ 369 ], and lectin receptors (see under glycans) [ 329 ] on various potential targets such as the cancer cells, BBB, and inflammation sites have rendered their respective ligands attractive targeting moieties. Compared to affinity molecules, the lure of such natural ligands lies mainly within their prevalence, stability, inexpensiveness, and low immunogenicity.…”