Transferrin-conjugated lipid-coated PLGA nanoparticles for targeted delivery of aromatase inhibitor 7α-APTADD to breast cancer cells

Abstract

Transferrin (Tf)-conjugated lipid-coated poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles carrying the aromatase inhibitor, 7α-(4′-amino)phenylthio-1,4-androstadiene-3,17-dione (7α-APTADD), were synthesized by a solvent injection method. Formulation parameters including PLGA-to-lipid, egg PC-to-TPGS, and drug-to-PLGA ratios and aqueous-to-organic phase ratio at the point of synthesis were optimized to obtain nanoparticles with desired sizes and drug loading efficiency. The optimal formulation had a drug loading efficiency of 36.3±3.4%, mean diameter of 170.3±7.6 nm and zeta potential of −18.9±1.5 mV. The aromatase inhibition activity of the nanoparticles was evaluated in SKBR-3 breast cancer cells. IC50 value of the Tf-nanoparticles was ranging from 0.77 to 1.21 nM, and IC50 value of the nanoparticles was ranging from 1.90 to 3.41 nM (n = 3). The former is significantly lower than the latter (p < 0.05). These results suggested that the aromatase inhibition activity of the Tf-nanoparticles was enhanced relative to that of the non-targeted nanoparticles, which was attributable to Tf receptor (TfR) mediated uptake. In conclusion, Tf-conjugated lipid-coated PLGA nanoparticles are potential vehicles for improving the efficiency and specificity of therapeutic delivery of aromatase inhibitors.

An Apoferritin‐based Drug Delivery System for the Tyrosine Kinase Inhibitor Gefitinib

“…[ 4,8 ] Both SKBR3 and MDA-MB-231 cells possess high levels of TfR1 [ 33 ] which would assist cellular uptake of H-AFt-encapsulated-Gefi tinib. [ 34 ] The greater SKBR3 growth inhibition by H-AFt compared to MDA-MB-231 implies greater sequestration of H-AFt by SKBR3 cells. Indeed, it has been shown previously that ferritin was not taken up by MDA-MB-231 cells.…”

Polylactide-co-glycolide nanoparticles for controlled delivery of anticancer agents

“…These results suggest that the aromatase inhibition activity of the transferrin nanoparticles was enhanced relative to that of the nontargeted nanoparticles, which was attributable to transferrin receptor-mediated uptake. 132 The α v β 3 integrin is an endothelial cell receptor for extracellular matrix proteins harboring the arginine-glycine-aspartic acid (RGD) sequence. 126 Wang et al conjugated doxorubicin to PLGA, and the nanoparticle surfaces were then linked with PEG and the RGD peptides to achieve both passive and active targeting functions.…”

Targeted Nanoparticles for Cancer Therapy

“…PLGA NPs loaded with the 7 -APTADD were significantly more effective preventing proliferation of the human breast cancer cell line SK-BR-3 than non-targeted NPs. These results suggested that the aromatase inhibition activity of the Tf-NPs was enhanced relative to that of the non-targeted NPs, which was attributable to TfR mediated uptake [87] Gan and coworkers observed that Tf-conjugated poly(lactide)-D--tocopheryl polyethylene glycol succinate diblock copolymer NPs loaded with Dtxl could be more efficient eliciting cytotoxicity against C6 glioma cells than other nontargeted formulations [88].…”