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. 2019 Oct 3:14:8001-8011.
doi: 10.2147/IJN.S226798. eCollection 2019.

Fabrication Of Dual pH/redox-Responsive Lipid-Polymer Hybrid Nanoparticles For Anticancer Drug Delivery And Controlled Release

Wanfu Men  1 , Peiyao Zhu  1 , Siyuan Dong  1 , Wenke Liu  1 , Kun Zhou  1 , Yu Bai  1 , Xiangli Liu  1 , Shulei Gong  1 , Can Yang Zhang  2 , Shuguang Zhang  1
Affiliations

Fabrication Of Dual pH/redox-Responsive Lipid-Polymer Hybrid Nanoparticles For Anticancer Drug Delivery And Controlled Release

Wanfu Men et al. Int J Nanomedicine. .

Abstract

Background: The development of biocompatible nanocarriers that can efficiently encapsulate and deliver anticancer drug to the tumor site and provide controlled release of cargos in response to the specific cues for cancer therapy is of great significance.

Methods: In this work, dual pH/redox-responsive fabrication of hybrid lipid-polymer nanoparticles (LPNPs) self-assembled from amphiphilic polymer poly(ethylene glycol) methyl ether-grafted disulfide-poly(β-amino esters) (PBAE-ss-mPEG) and PEGylated lipid were prepared and used as drug delivery carriers. The optimization of PEGylated lipid modification was confirmed by analysis of particle size, polydispersity index (PDI), cellular uptake, serum stability, and drug loading capacity. The pK b value of LPNPs was determined as 6.55, indicating the pH-sensitivity. The critical micelle concentration (CMC) values and zeta-potential of LPNPs at different pH values were investigated to confirm its pH-sensitivity. The morphology of LPNPs before and after incubation with reducing agent was imaged to study the redox-responsibility.

Results: The in vitro results showed that the drug had controlled release from LPNPs triggered by low pH and high concentration of reducing agent. Furthermore, the cytotoxicity of LPNPs was very low, and the doxorubicin (DOX)-loaded LPNPs could efficiently induce the death of tumor cells in comparison to free DOX.

Conclusion: All results demonstrated that the fabricated LPNPs could be potential anticancer drug delivery carriers with a pH/redox-triggered drug release profile, and PEGylated lipid modification might be a useful method to fabricate the drug delivery platform.

Keywords: anticancer; drug delivery; hybrid; lipid-polymer; pH-sensitive; redox-sensitive; stimuli-responsiveness.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Schematic illustration of self-assembly of hybrid lipid-polymer nanoparticles (LPNPs) loading anticancer drug DOX and controlled release profile triggered by pH and reducing agent.
Figure 2
Figure 2
Hydrodynamic diameter (A) and polydispersity index (PDI) of LPNPs formulated with a different amount of DSPE-mPEG measured by DLS (n=3, mean±SD). Cellular internalization (C) of LPNPs after incubation with 3LL cells for 2 hours determined by flow cytometry.
Figure 3
Figure 3
Hydrodynamic diameter (A) and polydispersity index (PDI) (B) of LPNPs after incubation in PBS (pH 7.4) with 20% FBS at 37°C for different time (n=3, mean±SD).
Figure 4
Figure 4
The acid-base titration curve (A) of the PMs and LPNPs (7% of DSPE-mPEG, mole ratio) solution. The CMCs (B) of PMs and LPNPs (7% of DSPE-mPEG, mole ratio) at different pH values (n=3, mean±SD). TEM images of LPNPs (7% of DSPE-mPEG, mole ratio) after incubation in PBS at pH 7.4 without (C) or with (D) DTT (10 mM) for 4 hours at 37°C. Scale bar = 500 nm.
Figure 5
Figure 5
In vitro release profiles of DOX from DOX-loaded PMs (A) and DOX-loaded LPNPs (B) in PBS at different conditions (pH 7.4, pH 6.5, pH 7.4 with 10 mM DTT, and pH 6.5 with 10 mM DTT) (n=3, mean±SD).
Figure 6
Figure 6
Cell viability of 3LL cells treated with blank PMs and LPNPs (A), free DOX, DOX-loaded PMs and DOX-loaded LPNPs (B) for 24 hours in concentration specified.
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