Dendrimer-Based Biocompatible Zwitterionic Micelles for Efficient Cellular Internalization and Enhanced Antitumor Effects

Abstract

Zwitterionic materials have been employed to achieve excellent biocompatibility and the well-suppressed nonspecific protein adsorption of nanoparticles. However, a thick and compact zwitterionic layer may prevent the modified nanoparticles from entering tumor cells, resulting in low cellular internalization efficiency. To address this problem, new biocompatible micelles (PPIMYC) with a thin zwitterionic layer were designed and prepared. Zwitterionic generation 2 polypropyleneimine dendrimers (G2 PPI) serve as the hydrophilic external shell, and N-(2-mercaptoethyl)­oleamide serves as the hydrophobic internal core. Drug-loaded dendritic micelles (PPIMYC-DOX-Ce6) were also prepared by self-assembly of PPIMYC with doxorubicin (DOX) and chlorin e6 (Ce6) to demonstrate chemo-photodynamic dual therapy. As potential drug delivery systems for antitumor therapy, PPIMYC-DOX-Ce6 exhibited sustained drug release under acidic conditions and high stability in fibrinogen solution. In addition, cytotoxicity studies showed an enhanced efficiency of PPIMYC-DOX-Ce6 in killing HeLa cells as compared to free DOX with or without irradiation (660 nm laser). More importantly, both flow cytometry and fluorescence microscopy results indicated that the cellular uptake efficiency of DOX was significantly enhanced in PPIMYC-DOX-Ce6-treated cells relative to free DOX treated cells. The intracellular internalization of PPIMYC-DOX-Ce6 was more efficient under acidic pH, representing the tumor environment, as compared to normal pH. This results from the pH sensitivity of the zwitterionic layer. Temperature was the only environmental factor affecting the cellular internalization process. It is believed that the enhanced intracellular internalization efficiency is due to the thin zwitterionic layer of PPIMYC-DOX-Ce6. The preparation scheme of zwitterionic micelles would offer a new strategy to design novel antitumor drug delivery systems with enhanced cellular internalization efficiency and high stability in a complex medium.

Zwitterionic Polymer Micelles with Dual Conjugation of Doxorubicin and Curcumin: Synergistically Enhanced Efficacy against Multidrug-Resistant Tumor Cells

“…The lower levels of Dox from pCB-Dox and Cur-pCB-Dox than the literature data are considered mainly due to the nonfouling characteristics of the zwitterionic pCB, which hindered the endocytosis of the micelles to some extent. To enhance the endocytosis of micelles or nanoparticles, surface decoration of micelles or nanoparticles by a specific tumor-targeting ligand, such as antibody, peptide, aptamer, polysaccharide, saccharide, folic acid, and so on, can largely enhance the cellular uptake of micelles or nanoparticles − since the targeting ligands could specifically bind to the receptor highly expressed at the surface of malignant cells.…”

Polyethyleneimine-Stabilized Platinum Nanoparticles as Peroxidase Mimic for Colorimetric Detection of Glucose

“…The stability of NPs was dependent on the zeta potential and polymer template. High zeta potential of NPs (>30 mV) means their good stability. , In addition, the polymer template inhibits agglomeration of NPs by steric effects. , As for Pt 50 -PEI NPs, electrostatic repulsion and steric hindrance between Pt 50 -PEI NP result in their high stability which was beneficial to catalytic oxidation of TMB for a long time . In short, Pt 50 -PEI NPs had high stability with a hydrodynamic size of ∼25 nm and slightly positive charge.…”

Ginkgo biloba leaf polysaccharide stabilized palladium nanoparticles with enhanced peroxidase-like property for the colorimetric detection of glucose

“…Furthermore, the biocompatibility of Pd 91 -GBLP NPs was evaluated by MTT assay and morphology observation. 46,47 As shown in Fig. 6a, cell viability of HeLa cells was higher than 92.3% when the concentration of Pd 91 -GBLP NPs was within 0-500 mg mL À1 .…”