Investigation of antitumor activities of trastuzumab delivered by PLGA nanoparticles

International Journal of Nanomedicine
Barbara ColzaniDavide Prosperi

Abstract

We report the development of an efficient antibody delivery system for the incorporation of trastuzumab (TZ) into poly(lactic-co-glycolic) acid nanoparticles (PLGA NPs). The aim of the work was to overcome the current limitations in the clinical use of therapeutic antibodies, including immunogenicity, poor pharmacokinetics, low tumor penetration and safety issues. Trastuzumab-loaded PLGA NPs (PLGA-TZ) were synthesized according to a double emulsion method. The same protocol was used to produce control batches of nonspecific IgG-loaded NPs and empty PLGA NPs. After release of TZ from PLGA NPs, the effects on the main biological activities of the antibody were evaluated on SKBR3 (human epidermal growth factor receptor 2 [HER2]-positive breast cancer cell line), including specific binding to HER2, phosphorylation of HER2 (Y1248), degradation of HER2 protein and antibody-dependent cell-mediated cytotoxicity (ADCC) mechanism. In addition, an MTT assay was performed for treating SKBR3 cells with PLGA NPs loaded with TZ and doxorubicin to evaluate the cytotoxic activity of the combined treatment. TZ was gradually released in a prolonged way over 30 days. The physical characterization performed with circular dichroism, Fourier transfor...Continue Reading

Citations

Dec 7, 2018·International Journal of Molecular Sciences·Suchithra Poilil SurendranYong Yeon Jeong
Feb 6, 2020·AAPS PharmSciTech·Nermin E ElerakyGiovanni M Pauletti
Oct 31, 2019·Journal of Hematology & Oncology·E KrasniqiP Vici
Aug 22, 2020·International Journal of Nanomedicine·Kyungeun Kim, Dongwoo Khang
Jul 14, 2019·Seminars in Cancer Biology·Balney RajithaGanji Purnachandra Nagaraju
May 6, 2021·Materials Science & Engineering. C, Materials for Biological Applications·Qiu-Ping FengShu-Qin Yu
Jun 26, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Salma B AbdelbakyIslam A Khalil
Jul 3, 2021·Materials·Hernán CortésGerardo Leyva-Gómez
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Safiye AkkınErem Bilensoy
Apr 14, 2020·Bioconjugate Chemistry·Jooneon ParkNicole F Steinmetz
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Methods Mentioned

BETA
protein folding
dynamic light scattering
electrophoresis
circular dichroism
flow cytometry
confocal microscopy
Assay
flow

Software Mentioned

Resolutions Pro
BeStSel

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