Dataset Information

Investigation of antitumor activities of trastuzumab delivered by PLGA nanoparticles.

ABSTRACT:

Background

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.

Materials and methods

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.

Results and discussion

TZ was gradually released in a prolonged way over 30 days. The physical characterization performed with circular dichroism, Fourier transform infrared and fluorescence spectroscopy of TZ after release demonstrated that no structural alterations occurred compared to the native antibody. In vitro experiments using SKBR3 cells showed that TZ released from PLGA NPs maintained the same biological activity of native TZ. PLGA NPs allowed a good co-encapsulation efficiency of TZ and doxorubicin resulting in improved therapy.

Conclusion

With the TZ case study, we demonstrate that the distinctive features of therapeutic monoclonal antibodies, including molecular targeting efficiency, capability to inhibit or properly affect the regulatory signaling pathways of cancer cells and stimulation of the ADCC, are fully preserved after loading into and release from PLGA NPs. In addition, PLGA NPs are shown to allow for the simultaneous incorporation of TZ and conventional chemotherapeutics, resulting in a potent antitumor nanodrug well suited for in situ combination and neoadjuvant therapy.

SUBMITTER: Colzani B

PROVIDER: S-EPMC5817418 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Investigation of antitumor activities of trastuzumab delivered by PLGA nanoparticles.

Colzani Barbara B Pandolfi Laura L Hoti Ada A Iovene Pietro Alessandro PA Natalello Antonino A Avvakumova Svetlana S Colombo Miriam M Prosperi Davide D

International journal of nanomedicine 20180214

<h4>Background</h4>We report the development of an efficient antibody delivery system for the incorporation of trastuzumab (TZ) into poly(lactic-<i>co</i>-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.<h4>Materials and methods</h4>Trastuzumab-loaded PLGA NPs (PLGA-TZ) were synthesized according to a double e ...[more]

PMID: 29491709

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Dataset Information

Investigation of antitumor activities of trastuzumab delivered by PLGA nanoparticles.

Background

Materials and methods

Results and discussion

Conclusion

Publications

Investigation of antitumor activities of trastuzumab delivered by PLGA nanoparticles.

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