Folate-containing reduction-sensitive lipid–polymer hybrid nanoparticles for targeted delivery of doxorubicin

Abstract

The development and evaluation of folate-targeted and reduction-triggered biodegradable nanoparticles are introduced to the research on targeted delivery of doxorubicin (DOX). This type of folate-targeted lipid-polymer hybrid nanoparticles (FLPNPs) is comprised of a poly(D,L-lactide-co-glycolide) (PLGA) core, a soybean lecithin monolayer, a monomethoxy-poly(ethylene glycol)-S-S-hexadecyl (mPEG-S-S-C16) reduction-sensitive shell, and a folic acid-targeted ligand. FLPNPs exhibited high size stability but fast disassembly in a simulated cancer cell reductive environment. The experiments on the release process in vitro revealed that as a reduction-sensitive drug delivery system, FLPNPs released DOX faster in the presence of 10 mM dithiothreitol (DTT). Results from flow cytometry, confocal image and in vitro cytotoxicity assays revealed that FLPNPs further enhanced cell uptake and generated higher cytotoxicity against human epidermoid carcinoma in the oral cavity than non-targeted redox-sensitive and targeted redox-insensitive controls. Furthermore, in vivo animal experiments demonstrated that systemic administration of DOX-loaded FLPNPs remarkably reduced tumor growth. Experiments on biodistribution of DOX-loaded FLPNPs showed that an increasing amount of DOX accumulated in the tumor. Therefore, FLPNPs formulations have proved to be a stable, controllable and targeted anticancer drug delivery system.

Codelivery of doxorubicin and triptolide with reduction-sensitive lipid–polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment

“…[10][11][12][13][14][15][16][17][18] We previously reported the preparation of a new type of hybrid nanoparticle LPNPs using an amphiphilic reduction-sensitive polymer of monomethoxy-poly(ethylene glycol)-S-S-hexadecyl (mPEG-S-S-C 16 ) to achieve intracellular release and then improve the therapeutic effect. [19][20][21] The amphiphilic polymer mPEG-S-S-C 16 containing a disulfide bond could maintain the stability of this formulation and serve as a switch to trigger drug release. The system of LPNPs was evaluated in vitro and in vivo and was proven as a potential drug carrier.…”

Redox-sensitive Pluronic F127-tocopherol micelles: synthesis, characterization, and cytotoxicity evaluation

“…20,21 Disulfide bond is stable under normal physiological conditions yet responsive to the reductive environment (eg, GSH) of intracellular fluids in cancer cells, indicating that disulfide bonds can be used as the linker of hydrophilic and hydrophobic portions in the redox-sensitive polymeric micelles for controlling the delivery of intracellular drug. 22 Here, we synthesized a redox-sensitive F127-SS-TOC polymer using a disulfide bond to link F127 and TOC, which formed nanomicellar structures in aqueous solution and ruptured in the presence of glutathione (GSH, 2-10 mM) ( Figure 1) owing to a redox reaction. F127-SS-TOC polymer was synthesized and confirmed with 1 H nuclear magnetic resonance spectra ( 1 H NMR) and Fourier transform infrared spectra (FTIR).…”

Near-infrared light-triggered theranostics for tumor-specific enhanced multimodal imaging and photothermal therapy

“…The lipid-polymer hybrid nanoparticles, which have various advantages of polymeric nanoparticles and liposomes, have become a robust delivery platform with properties such as excellent stability, tunability, high drug encapsulation, and sustained drug release. 28 Liposome was an ideal CAs carrier to clearly display the extent of cancer and monitors the treatment effect in real time. 29,30 In addition, previous research has suggested that CAs have better MRI contrast effect or stronger fluorescence intensity when the CAs were released from the nanoparticles.…”