Transferrin-conjugated Docetaxel-PLGA nanoparticles for tumor targeting: Influence on MCF-7 cell cycle

Sajan Jose, Thomas A. Cinu, Rosmy Sebastian, M. H. Shoja, N. A. Aleykutty, Alessandra Durazzo, Massimo Lucarini, Antonello Santini, Eliana B. Souto

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number1905
JournalPolymers
Volume11
Issue number11
DOIs
Publication statusPublished - 01-11-2019
Externally publishedYes

Fingerprint

glycolic acid
docetaxel
Transferrin
Tumors
Cells
Nanoparticles
Acids
Ligands
Milk
Kinetics
Diamines

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Polymers and Plastics

Cite this

Jose, S., Cinu, T. A., Sebastian, R., Shoja, M. H., Aleykutty, N. A., Durazzo, A., ... Souto, E. B. (2019). Transferrin-conjugated Docetaxel-PLGA nanoparticles for tumor targeting: Influence on MCF-7 cell cycle. Polymers, 11(11), [1905]. https://doi.org/10.3390/polym11111905
Jose, Sajan ; Cinu, Thomas A. ; Sebastian, Rosmy ; Shoja, M. H. ; Aleykutty, N. A. ; Durazzo, Alessandra ; Lucarini, Massimo ; Santini, Antonello ; Souto, Eliana B. / Transferrin-conjugated Docetaxel-PLGA nanoparticles for tumor targeting : Influence on MCF-7 cell cycle. In: Polymers. 2019 ; Vol. 11, No. 11.
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abstract = "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.",
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Jose, S, Cinu, TA, Sebastian, R, Shoja, MH, Aleykutty, NA, Durazzo, A, Lucarini, M, Santini, A & Souto, EB 2019, 'Transferrin-conjugated Docetaxel-PLGA nanoparticles for tumor targeting: Influence on MCF-7 cell cycle', Polymers, vol. 11, no. 11, 1905. https://doi.org/10.3390/polym11111905

Transferrin-conjugated Docetaxel-PLGA nanoparticles for tumor targeting : Influence on MCF-7 cell cycle. / Jose, Sajan; Cinu, Thomas A.; Sebastian, Rosmy; Shoja, M. H.; Aleykutty, N. A.; Durazzo, Alessandra; Lucarini, Massimo; Santini, Antonello; Souto, Eliana B.

In: Polymers, Vol. 11, No. 11, 1905, 01.11.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Transferrin-conjugated Docetaxel-PLGA nanoparticles for tumor targeting

T2 - Influence on MCF-7 cell cycle

AU - Jose, Sajan

AU - Cinu, Thomas A.

AU - Sebastian, Rosmy

AU - Shoja, M. H.

AU - Aleykutty, N. A.

AU - Durazzo, Alessandra

AU - Lucarini, Massimo

AU - Santini, Antonello

AU - Souto, Eliana B.

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N2 - 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.

AB - 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.

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Jose S, Cinu TA, Sebastian R, Shoja MH, Aleykutty NA, Durazzo A et al. Transferrin-conjugated Docetaxel-PLGA nanoparticles for tumor targeting: Influence on MCF-7 cell cycle. Polymers. 2019 Nov 1;11(11). 1905. https://doi.org/10.3390/polym11111905