Tuning the protein corona of PLGA nanoparticles: Characterization of trastuzumab adsorption behavior and its cellular interaction with breast cancer cell lines

Spreen, Hendrik; Barth, Christina; Keuter, Lucas; Mulac, Dennis; Humpf, Hans‐Ulrich; Langer, Klaus

doi:10.1016/j.jddst.2022.103543

Cited by 4 publications

(4 citation statements)

References 22 publications

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“…To study protein binding and quantification, the removal of the proteins from medicinal nanoparticles with trypsin has been demonstrated. 85,86…”

Section: Nanoparticlesmentioning

confidence: 99%

“…To study protein binding and quantification, the removal of the proteins from medicinal nanoparticles with trypsin has been demonstrated. 85,86 Whilst already studied and implemented in the field of biopolymers, the application of IMERs on synthetic polymers is virtually unexplored. In 2019, we attempted to perform online enzymatic digestion on polyester NPs using an IMER that was prepared in-house.…”

Section: Sample Transformation For Polymeric Nanoparticlesmentioning

confidence: 99%

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Sample transformation in online separations: how chemical conversion advances analytical technology

van der Zon,

Verduin,

van den Hurk

et al. 2024

Chem. Commun.

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“…To study protein binding and quantification, the removal of the proteins from medicinal nanoparticles with trypsin has been demonstrated. 85,86…”

Section: Nanoparticlesmentioning

confidence: 99%

Section: Sample Transformation For Polymeric Nanoparticlesmentioning

confidence: 99%

Sample transformation in online separations: how chemical conversion advances analytical technology

van der Zon,

Verduin,

van den Hurk

et al. 2024

Chem. Commun.

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“…At the same time, its ability to bind to the receptor and penetrate cancer cells and its therapeutic effects were superior to free antibodies [ 37 ]. Several studies have shown not only trastuzumab loading into a polymer particle but also adsorption on the NP surface, with the formation of a rigid protein corona [ 38 ]. Specific cell binding gives us a reason to believe that trastuzumab remains available for receptor recognition within the particle.…”

Section: Introductionmentioning

confidence: 99%

Targeted PLGA–Chitosan Nanoparticles for NIR-Triggered Phototherapy and Imaging of HER2-Positive Tumors

Kotelnikova,

Shipunova,

Deyev

2023

Pharmaceutics

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Targeted medicine uses the distinctive features of cancer cells to find and destroy tumors. We present human epidermal growth factor receptor 2 (HER2)-targeted PLGA–chitosan nanoparticles for cancer therapy and visualization. Loading with two near-infrared (NIR) dyes provides imaging in the NIR transparency window and phototherapy triggered by 808 nm light. Nile Blue (NB) is a biocompatible solvatochromic NIR dye that serves as an imaging agent. Laser irradiation of IR-780 dye leads to a temperature rise and the generation of reactive oxygen species (ROS). Resonance energy transfer between two dyes allows visualization of tumors in a wide range of visible and IR wavelengths. The combination of two NIR dyes enables the use of nanoparticles for diagnostics only or theranostics. Modification of poly(lactic-co-glycolic acid) (PLGA)–chitosan nanoparticles with trastuzumab provides an efficient nanoparticle uptake by tumor cells and promotes more than sixfold specificity towards HER2-positive cells, leading to a synergistic anticancer effect. We demonstrate optical imaging of the HER2-positive mouse mammary tumor and tumor-specific accumulation of PLGA–IR-780–NB nanoparticles in vivo after intravenous administration. We managed to achieve almost complete suppression of the proliferative activity of cells in vitro by irradiation with an 808 nm laser with a power of 0.27 W for 1 min at a concentration at which nanoparticles are nontoxic to cells in the dark.

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“…Due to their harmless properties, controlled release, biocompatibility, and biodegradability, PLGA-based carriers have been already used to reduce toxicity and improve mAbs therapy. 12,[14][15][16][17][18] In addition, PLGA carriers have several advantages over direct systemic injection of TZ, including longer residence time in the bloodstream and lower immunogenicity. 15 Nanoencapsulation also allows for longer formulation shelf life and slows in vivo degradation with prolonged release of the entrapped mAb, which could lead to fewer administrations and improved patient compliance.…”

Section: Introductionmentioning

confidence: 99%

Development of High-Loading Trastuzumab PLGA Nanoparticles: A Powerful Tool Against HER2 Positive Breast Cancer Cells

Caputo,

Barisciano,

Mulè

et al. 2023

IJN

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Background Trastuzumab, a therapeutic monoclonal antibody directed against HER2, is routinely used to treat HER2-positive breast cancer with a good response rate. However, concerns have arisen in the clinical practice due to adverse side effects. One way to overcome these limitations is to encapsulate trastuzumab in nanoparticles to improve cytotoxic activity, increase intracellular drug concentrations, escape the immune system and avoid systemic degradation of the drug in vivo. Methods A double emulsion method was used to encapsulate trastuzumab into poly(lactic-co-glycolic) nanoparticles, effective for their biocompatibility and biodegradability. These nanocarriers, hereafter referred to as TZPs, were characterised in terms of size, homogeneity, zeta potential and tested for their stability and drug release kinetics. Finally, the TZPs cytotoxicity was assessed in vitro on the HER2 positive SKBR3 breast cancer cell line and compared to free trastuzumab. Results The TZPs were stable, homogeneous in size, with a reduced zeta potential. They showed higher encapsulation efficiency and drug loading, a prolonged trastuzumab release kinetics that retained its physicochemical properties and functionality. TZPs showed a stronger cytotoxicity and increased apoptosis than similar doses of free trastuzumab in the cell line analysed. Confocal microscopy and flow cytometry assessed TZPs and trastuzumab cellular uptake while Western blot evaluated downstream signalling, overall HER2 content and shedding. Conclusion TZPs exert more robust effects than free trastuzumab via a dual mode of action: TZPs are taken up by cells through an endocytosis mechanism and release the drug intracellularly for longer time. Additionally, the TZPs that remain in the extracellular space release trastuzumab which binds to the cognate receptor and impairs downstream signalling. This is the sole modality used by free trastuzumab. Remarkably, half dose of TZPs is as efficacious as the highest dose of free drug supporting their possible use for drug delivery in vivo.

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Tuning the protein corona of PLGA nanoparticles: Characterization of trastuzumab adsorption behavior and its cellular interaction with breast cancer cell lines

Cited by 4 publications

References 22 publications

Sample transformation in online separations: how chemical conversion advances analytical technology

Sample transformation in online separations: how chemical conversion advances analytical technology

Targeted PLGA–Chitosan Nanoparticles for NIR-Triggered Phototherapy and Imaging of HER2-Positive Tumors

Development of High-Loading Trastuzumab PLGA Nanoparticles: A Powerful Tool Against HER2 Positive Breast Cancer Cells

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