Novel silk fibroin nanoparticles incorporated silk fibroin hydrogel for inhibition of cancer stem cells and tumor growth

Abstract

BackgroundA multi-drug delivery platform is needed as the intra-tumoral heterogeneity of cancer leads to different drug susceptibility. Cancer stem cells (CSCs), a small population of tumor cells responsible for tumor seeding and recurrence, are considered chemotherapy-resistant and have been reported to be sensitive to salinomycin (Sal) instead of paclitaxel (Ptx). Here we report a novel silk fibroin (SF) hydrogel-loading Sal and Ptx by incorporating drug-loaded silk fibroin nanoparticles (SF-NPs) to simultaneously kill CSCs and non-CSCs.MethodsUsing the method we have previously reported to prepare Ptx-loaded SF-NPs (Ptx-SF-NPs), Sal-loaded SF-NPs (Sal-SF-NPs) were fabricated under mild and non-toxic conditions. The drug-loaded SF-NPs were dispersed in the ultrasound processed SF solution prior to gelation.ResultsThe resulting SF hydrogel (Sal-Ptx-NP-Gel) retained its injectable properties, exhibited bio-degradability and demonstrated homogeneous drug distribution compared to the non-NP incorporated hydrogel. Sal-Ptx-NP-Gel showed superior inhibition of tumor growth compared to single drug-loaded hydrogel and systemic dual drug administration in the murine hepatic carcinoma H22 subcutaneous tumor model. Sal-Ptx-NP-Gel also significantly reduced CD44+CD133+ tumor cells and demonstrated the least tumor formation in the in vivo tumor seeding experiment, indicating superior inhibition of cancer stem cells.ConclusionThese results suggest that SF-NPs incorporated SF hydrogel is a promising drug delivery platform, and Sal-Ptx-NP-Gel could be a novel and powerful locoregional tumor treatment regimen in the future.

Paclitaxel-Loaded Silk Fibroin Nanoparticles: Method Validation by UHPLC-MS/MS to Assess an Exogenous Approach to Load Cytotoxic Drugs

“…Despite the fact that the in vitro effectiveness of PTX was not modified by the encapsulation in SFNs, we assume that our nanosystems could improve the cytotoxicity of PTX when in vivo administered. In fact, different authors demonstrated that the use of silk nanoparticles, as anticancer drug delivery systems, can increase the drug accumulation in target cancer tissues and reduce the efflux pump-mediated drug resistance [7,48]. Furthermore, silk fibroin nanoparticles can be functionalized, with the peptide motif RGD (arginine-glycine-aspartic acid), to enhance their interaction with tumor tissues and to reduce side effects [49,50].…”

Recent advances in drug delivery systems for targeting cancer stem cells

“…Therefore, several suitable delivery carriers and systems have been developed. Table 4 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 , 158 , 159 , 160 , 161 , 162 , 163 , 164 , 165 , 166 , 167 , 168 , 169 , 170 , 171 , 172 , 173 , 174 , 175 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 summarizes recent DDSs for targeting CSC genes and epigenetics.…”

“…Therefore, it is wise to combine conventional anticancer agents and anti-CSC agents for improved therapeutic response 144 , 145 . Recently, many researchers have reported successful development of co-delivery systems for combination therapy ( Table 5 30 , 31 , 73 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 , 158 , 159 , 160 , 161 , 162 , 163 , 164 , 165 , 166 , 167 , 168 , 169 , 170 , 171 , 172 , 173 , 174 , 175 ; Fig. 7 30 , 31 ).…”

Recent trends in protein and peptide-based biomaterials for advanced drug delivery

“…The dual drug-loaded hydrogel had homogeneous drug distribution and exhibited increased tumor inhibition compared to the single drug-loaded hydrogel, as evidenced by fewer CD44 + CD133+ tumor cells in vivo. Because paclitaxel and salinomycin interacted differently with SF, their release profiles were different, with paclitaxel showing sustained release and salinomycin an initial burst release [ 92 ]. Gangrade et al introduced carbon nanotubes into SF hydrogels to construct an on-demand, tumor-targeting system [ 93 ].…”