Transferrin-Conjugated Docetaxel–PLGA Nanoparticles for Tumor Targeting: Influence on MCF-7 Cell Cycle

Targeted drug delivery systems are commonly used to improve the therapeutic index of anti-cancer drugs by increasing their selectivity and reducing systemic distribution and toxicity. Ligand-conjugated nanoparticles (NPs) can be effectively applied for active chemotherapeutic targeting to overexpressed receptors of tumor cells. In this study, transferrin (Tf) was successfully conjugated with poly-L-lactic-co-glycolic acid (PLGA) using ethylene diamine confirmed by NMR, for the loading of docetaxel trihydrate (DCT) into PLGA nanoparticles (NPs). The DCT-loaded Tf-conjugated PLGA NPs were produced by an emulsion-solvent evaporation technique, and a 32 full factorial design was used to optimize the nanoparticle formulations. The DCT-loaded Tf-conjugated PLGA NPs were characterized by FTIR spectroscopy, differential scanning calorimetry, powder X-ray diffraction (PXRD), TEM, particle size, and zeta potential analysis. In vitro release kinetics confirmed that release of DCT from the designed formulations followed a zero-order kinetics and a diffusion controlled non-Fickian release profile. The DCT-loaded Tf-conjugated PLGA NPs were evaluated in vitro in MCF-7 cells for bioactivity assessment. Cytotoxicity studies confirmed that the Tf-conjugated PLGA NPs were more active than the non-conjugated counterparts. Cell uptake studies re-confirmed the ligand-mediated active targeting of the formulated NPs. From the cell cycle analysis, the anti-cancer activity of DCT-loaded Tf-conjugated PLGA NPs was shown to occur by arresting the G2/M phase

Correction: Jose et al. Transferrin-Conjugated Docetaxel–PLGA Nanoparticles for Tumor Targeting: Influence on MCF-7 Cell Cycle. <i>Polymers</i> 2019, <i>11</i>, 1905

In the original publication [...

Transferrin-conjugated docetaxel-PLGA nanoparticles for tumor targeting: influence on MCF-7 cell cycle

Supplementary Materials: The following are available online at http://www.mdpi.com/2073-4360/11/11/1905/s1, Figure S1. FTIR spectrum of docetaxel trihydrate (DCT) (upper), of physical mixture of docetaxel trihydrate, transferrin (Tf) and PLGA (middle), and of DCT-loaded Tf-conjugated PLGA NPs (lower); Figure S2. DSC thermogram of PLGA (A), transferrin (B), docetaxel trihydrate (C), their physical mixture (D) and of DCT-loaded Tf-conjugated PLGA NPs (E); Figure S3. (A) X-ray diffraction pattern of docetaxel trihydrate, (B) physical mixture of docetaxel trihydrate, transferrin and PLGA, and of (C) DCT-loaded Tf-conjugated PLGA NPs. Figure S4. (A) Particle size distribution and average particle size and (B) zeta potential of DCT-loaded Tf-conjugated PLGA NPs.Targeted drug delivery systems are commonly used to improve the therapeutic index of anti-cancer drugs by increasing their selectivity and reducing systemic distribution and toxicity. Ligand-conjugated nanoparticles (NPs) can be effectively applied for active chemotherapeutic targeting to overexpressed receptors of tumor cells. In this study, transferrin (Tf) was successfully conjugated with poly-l-lactic-co-glycolic acid (PLGA) using ethylene diamine confirmed by NMR, for the loading of docetaxel trihydrate (DCT) into PLGA nanoparticles (NPs). The DCT-loaded Tf-conjugated PLGA NPs were produced by an emulsion-solvent evaporation technique, and a 32 full factorial design was used to optimize the nanoparticle formulations. The DCT-loaded Tf-conjugated PLGA NPs were characterized by FTIR spectroscopy, differential scanning calorimetry, powder X-ray diffraction (PXRD), TEM, particle size, and zeta potential analysis. In vitro release kinetics confirmed that release of DCT from the designed formulations followed a zero-order kinetics and a diffusion controlled non-Fickian release profile. The DCT-loaded Tf-conjugated PLGA NPs were evaluated in vitro in MCF-7 cells for bioactivity assessment. Cytotoxicity studies confirmed that the Tf-conjugated PLGA NPs were more active than the non-conjugated counterparts. Cell uptake studies re-confirmed the ligand-mediated active targeting of the formulated NPs. From the cell cycle analysis, the anti-cancer activity of DCT-loaded Tf-conjugated PLGA NPs was shown to occur by arresting the G2/M phase.The authors would like to acknowledge the financial support of All India Council for Technical Education (AICTE), New Delhi, India, under Research Promotion Scheme (RPS 2012–2013). The authors are also thankful to the Portuguese Foundation for Science and Technology (FCT/MEC) for funding the project M-ERA-NET-0004/2015 (PAIRED), through national funds and co-financed by FEDER under the Partnership Agreement PT2020. The authors acknowledge the support of the research project: Nutraceutica come supporto nutrizionale nel paziente oncologico, CUP: B83D18000140007.info:eu-repo/semantics/publishedVersio