Transferrin-Modified Doxorubicin-Loaded Biodegradable Nanoparticles Exhibit Enhanced Efficacy in Treating Brain Glioma-Bearing Rats

Abstract

Doxorubicin (Dox) is widely used for the treatment of solid tumors but its clinical utility on glioma is limited. In this study, we developed a novel nano-scale drug delivery system employing biodegradable nanoparticle (NP) as carriers to load Dox. Transferrin (Tf) was conjugated to the surface of NP to specifically target the NP to glioma. Tf-NP-Dox was prepared via emulsification-solvent evaporation method, and characterized for the size, Drug loading capacity (DLC), entrapment efficiency, and Tf number on the surface. The antitumor efficiency in vitro was evaluated via CCK-8 assay. The transmembrane transportation was evaluated via HPLC assay. The antitumor efficiency in vivo was assessed in C6 glioma intracranial implant rat model. The average diameter of Tf-NP-Dox was 100 nm with ∼32 Tf molecules on the surface. DLC was 4.4%. CCK-8 assay demonstrated much stronger cytotoxicity of Tf-NP-Dox to C6 glioma cells compared to NP-Dox or Dox. HPLC assay showed that Tf-NP-Dox transported Dox into C6 cells with high efficiency. In vivo, Tf-NP-Dox could transport Dox into tumors compare to contralateral part, with tumor inhibitory ratio and survival higher than NP-Dox or Dox. Taken together, our results suggest that Tf-NP-Dox exhibits better therapeutic effects against glioma both in vitro and in vivo, and is a potential nano-scale drug delivery system for glioma chemotherapy.

Enhanced efficacy of combined temozolomide and bromodomain inhibitor therapy for gliomas using targeted nanoparticles

“…2b ). Our findings are consistent with studies demonstrating transferrin receptor expression in U87MG 12 and GL261 13 cells, suggesting that transferrin would be suitable as a ligand for our NPs for assessing receptor-mediated transcytosis and tumor targeting as previously reported in the literature 14 , 15 . We first assessed the ability of U87MG and GL261 cells to internalize Tf-NPs in vitro.…”

Use of Ferritin-Based Metal-Encapsulated Nanocarriers as Anticancer Agents

“…CD71 expression is particularly increased in metastatic and drug resistant tumors [33][34][35][36][37][38]. This makes CD71 both a tumor marker and a possible system for the delivery of small-molecule drugs to these cells by CD71-mediated endocytosis [39][40][41][42][43][44]. Recently, CD71 was identified as the receptor for HFt [22], with distinct binding sites for HFt and transferrin [45].…”

Functional Nanovalves on Protein-Coated Nanoparticles for In vitro and In vivo Controlled Drug Delivery

“…Iron is carried into the cell by the 79 kD transmembrane protein, transferrin (Tf), which can be exploited to increase delivery payload of therapeutics and maintain a localized region of treatment. Our group as well as others have successfully shown the enhanced delivery of therapeutics by transferrin‐modified nanoparticles that induce receptor‐mediated endocytosis in cancer cells . We have demonstrated the enhanced delivery of delivery hydrophobic drugs (camptothecin, taxol) with the folate‐ and transferrin‐modified MSNs, relying on the hydrophobic and hydrophilic forces to retain the hydrophobic cargo inside the MSN as it travels through the aqueous cellular media.…”