Transferrin-modified nanostructured lipid carriers as multifunctional nanomedicine for codelivery of DNA and doxorubicin

Abstract

Background Nanostructured lipid carriers (NLC), composed of solid and liquid lipids, and surfactants are potentially good colloidal drug carriers. The aim of this study was to develop surface-modified NLC as multifunctional nanomedicine for codelivery of enhanced green fluorescence protein plasmid (pEGFP) and doxorubicin (DOX). Methods Two different nanocarriers: pEGFP- and DOX-loaded NLC, and solid lipid nanoparticles (SLN) were prepared. Transferrin-containing ligands were used for the surface coating of the vectors. Their average size, zeta potential, and drug encapsulation capacity were evaluated. In vitro transfection efficiency of the modified vectors was evaluated in human alveolar adenocarcinoma cell line (A549 cells), and in vivo transfection efficiency of the modified vectors was evaluated in a mouse bearing A549 cells model. Results Transferrin-modified DOX and pEGFP coencapsulated NLC (T-NLC) has a particle size of 198 nm and a +19 mV surface charge. The in vitro cell viabilities of the T-NLC formulations were over 80% compared with the control. T-NLC displayed remarkably greater gene transfection efficiency and enhanced antitumor activity than DOX- and pEGFP-coencapsulated SLN in vivo. Conclusion The results demonstrate that T-NLC noticeably enhanced antitumor activity through the combination of gene therapy with chemotherapy. Also coating of active transferrin improved the lung cancer cell-targeting of the carriers. In summary, the novel gene and drug delivery system offers a promising strategy for the treatment of lung cancer.

Transferrin-Modified Nanoparticles for Photodynamic Therapy Enhance the Antitumor Efficacy of Hypocrellin A

“…Remarkable tumor inhibition in TF-HA- CMC-PLGA NPs group indicated that the potential superiority of TDDS. We concluded the different PDT efficacy in vivo that nanocarrier could improve the water-solubility and bioavailability of HA and TFR-mediated endocytic pathway could improve the cellular uptake of TF-modified nanoparticles within TFR positive cancer cells (Han et al, 2014 ; Guo et al, 2017 ). Body weight of mice reflects the health condition, so it is an indispensable factor to monitor.…”

“…The strategy of utilizing TF/TFR as a drug targeting carrier is based on the overexpression of TFR on the surface of tumor cells. Han et al have reported that a TF-modified multifunctional nanomedicine noticeably enhanced antitumor activity and improved the lung cancer cell-targeting in a mouse bearing A549 cells model (Han et al, 2014 ). Based on this premise, we designed a TDDS which had an active targeted ligand and could promote the water-solubility of HA.…”

“…We developed a TDDS to increase the T/N ratio and reduce side effects. We chose A549 cells (TFR positive) and NIH-3T3 cells (TFR negative) because of their differential TFR expression levels (Han et al, 2014 ; Muthu et al, 2015 ). On the basis of dark cytotoxicity test, we observed that cell survival rate of A549 cells and NIH-3T3 cells both had a high cell survival rate.…”

Colorectal cancer combination therapy using drug and gene co-delivered, targeted poly(ethylene glycol)-ε-poly(caprolactone) nanocarriers

“…GEE of NCs was determined by PicoGreen ® fluorometry assay. 28 It was calculated according to the linear calibration curve of pEGFP, according to the equation: (weight of total pEGFP - free pEGFP)/(weight of total pEGFP)×100.…”

<p>Targeted Therapy for Hepatocellular Carcinoma: Co-Delivery of Sorafenib and Curcumin Using Lactosylated pH-Responsive Nanoparticles</p>

“…8 These carriers include polymeric nanoparticles, liposomes, micelles, dendrimers, and so on. 9 The application of nanocarriers in the treatment of HCC is timely and has been recently reviewed. 10 Nanocarriers can be modified with specific ligands which can assist in targeting and internalization of the drugs to specific cell populations, such as cancer cells.…”