Surface antibody changes protein corona both in human and mouse serum but not final opsonization and elimination of targeted polymeric nanoparticles
Abstract Background Nanoparticles represent one of the most important innovations in the medical field. Among nanocarriers, polymeric nanoparticles (PNPs) attracted much attention due to their biodegradability, biocompatibility, and capacity to increase efficacy and safety of encapsulated drugs. Ano...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-023-02134-4 |
| _version_ | 1797451607860838400 |
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| author | Sara Capolla Federico Colombo Luca De Maso Prisca Mauro Paolo Bertoncin Thilo Kähne Alexander Engler Luis Núñez Ruben Spretz Gustavo Larsen Michele Dal Bo Giuseppe Toffoli Paolo Macor |
| author_facet | Sara Capolla Federico Colombo Luca De Maso Prisca Mauro Paolo Bertoncin Thilo Kähne Alexander Engler Luis Núñez Ruben Spretz Gustavo Larsen Michele Dal Bo Giuseppe Toffoli Paolo Macor |
| author_sort | Sara Capolla |
| collection | DOAJ |
| description | Abstract Background Nanoparticles represent one of the most important innovations in the medical field. Among nanocarriers, polymeric nanoparticles (PNPs) attracted much attention due to their biodegradability, biocompatibility, and capacity to increase efficacy and safety of encapsulated drugs. Another important improvement in the use of nanoparticles as delivery systems is the conjugation of a targeting agent that enables the nanoparticles to accumulate in a specific tissue. Despite these advantages, the clinical translation of therapeutic approaches based on nanoparticles is prevented by their interactions with blood proteins. In fact, the so-formed protein corona (PC) drastically alters the biological identity of the particles. Adsorbed activated proteins of the complement cascade play a pivotal role in the clearance of nanoparticles, making them more easily recognized by macrophages, leading to their rapid elimination from the bloodstream and limiting their efficacy. Since the mouse is the most used preclinical model for human disease, this work compared human and mouse PC formed on untargeted PNPs (uPNPs) and targeted PNPs (tPNPs), paying particular attention to complement activation. Results Mouse and human serum proteins adsorbed differently to PNPs. The differences in the binding of mouse complement proteins are minimal, whereas human complement components strongly distinguish the two particles. This is probably due to the human origin of the Fc portion of the antibody used as targeting agent on tPNPs. tPNPs and uPNPs mainly activate complement via the classical and alternative pathways, respectively, but this pattern did not affect their binding and internalization in macrophages and only a limited consumption of the activity of the human complement system was documented. Conclusions The results clearly indicate the presence of complement proteins on PNPs surface but partially derived from an unspecific deposition rather than an effective complement activation. The presence of a targeting antibody favors the activation of the classical pathway, but its absence allows an increased activation of the alternative pathway. This results in similar opsonization of both PNPs and similar phagocytosis by macrophages, without an impairment of the activity of circulating complement system and, consequently, not enhancing the susceptibility to infection. Graphical abstract |
| first_indexed | 2024-03-09T14:57:06Z |
| format | Article |
| id | doaj.art-62e01429a3cc4ca498bd80beda0dc175 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-03-09T14:57:06Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-62e01429a3cc4ca498bd80beda0dc1752023-11-26T14:08:25ZengBMCJournal of Nanobiotechnology1477-31552023-10-0121112010.1186/s12951-023-02134-4Surface antibody changes protein corona both in human and mouse serum but not final opsonization and elimination of targeted polymeric nanoparticlesSara Capolla0Federico Colombo1Luca De Maso2Prisca Mauro3Paolo Bertoncin4Thilo Kähne5Alexander Engler6Luis Núñez7Ruben Spretz8Gustavo Larsen9Michele Dal Bo10Giuseppe Toffoli11Paolo Macor12Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico (CRO) di Aviano, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS)Institute for Molecular Systems Engineering and Advanced Materials (IMSEAM), Ruprecht-Karls-Universität HeidelbergDepartment of Life Sciences, University of TriesteDepartment of Life Sciences, University of TriesteDepartment of Life Sciences, University of TriesteInstitute of Exptl. Internal Medicine, Medical Faculty, Otto von Guericke UniversityInstitute of Exptl. Internal Medicine, Medical Faculty, Otto von Guericke UniversityBioTarget IncBioTarget IncBioTarget IncExperimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico (CRO) di Aviano, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS)Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico (CRO) di Aviano, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS)Department of Life Sciences, University of TriesteAbstract Background Nanoparticles represent one of the most important innovations in the medical field. Among nanocarriers, polymeric nanoparticles (PNPs) attracted much attention due to their biodegradability, biocompatibility, and capacity to increase efficacy and safety of encapsulated drugs. Another important improvement in the use of nanoparticles as delivery systems is the conjugation of a targeting agent that enables the nanoparticles to accumulate in a specific tissue. Despite these advantages, the clinical translation of therapeutic approaches based on nanoparticles is prevented by their interactions with blood proteins. In fact, the so-formed protein corona (PC) drastically alters the biological identity of the particles. Adsorbed activated proteins of the complement cascade play a pivotal role in the clearance of nanoparticles, making them more easily recognized by macrophages, leading to their rapid elimination from the bloodstream and limiting their efficacy. Since the mouse is the most used preclinical model for human disease, this work compared human and mouse PC formed on untargeted PNPs (uPNPs) and targeted PNPs (tPNPs), paying particular attention to complement activation. Results Mouse and human serum proteins adsorbed differently to PNPs. The differences in the binding of mouse complement proteins are minimal, whereas human complement components strongly distinguish the two particles. This is probably due to the human origin of the Fc portion of the antibody used as targeting agent on tPNPs. tPNPs and uPNPs mainly activate complement via the classical and alternative pathways, respectively, but this pattern did not affect their binding and internalization in macrophages and only a limited consumption of the activity of the human complement system was documented. Conclusions The results clearly indicate the presence of complement proteins on PNPs surface but partially derived from an unspecific deposition rather than an effective complement activation. The presence of a targeting antibody favors the activation of the classical pathway, but its absence allows an increased activation of the alternative pathway. This results in similar opsonization of both PNPs and similar phagocytosis by macrophages, without an impairment of the activity of circulating complement system and, consequently, not enhancing the susceptibility to infection. Graphical abstracthttps://doi.org/10.1186/s12951-023-02134-4Polymeric nanoparticlesMouse serumHuman serumHuman plasmaComplement systemMacrophages |
| spellingShingle | Sara Capolla Federico Colombo Luca De Maso Prisca Mauro Paolo Bertoncin Thilo Kähne Alexander Engler Luis Núñez Ruben Spretz Gustavo Larsen Michele Dal Bo Giuseppe Toffoli Paolo Macor Surface antibody changes protein corona both in human and mouse serum but not final opsonization and elimination of targeted polymeric nanoparticles Journal of Nanobiotechnology Polymeric nanoparticles Mouse serum Human serum Human plasma Complement system Macrophages |
| title | Surface antibody changes protein corona both in human and mouse serum but not final opsonization and elimination of targeted polymeric nanoparticles |
| title_full | Surface antibody changes protein corona both in human and mouse serum but not final opsonization and elimination of targeted polymeric nanoparticles |
| title_fullStr | Surface antibody changes protein corona both in human and mouse serum but not final opsonization and elimination of targeted polymeric nanoparticles |
| title_full_unstemmed | Surface antibody changes protein corona both in human and mouse serum but not final opsonization and elimination of targeted polymeric nanoparticles |
| title_short | Surface antibody changes protein corona both in human and mouse serum but not final opsonization and elimination of targeted polymeric nanoparticles |
| title_sort | surface antibody changes protein corona both in human and mouse serum but not final opsonization and elimination of targeted polymeric nanoparticles |
| topic | Polymeric nanoparticles Mouse serum Human serum Human plasma Complement system Macrophages |
| url | https://doi.org/10.1186/s12951-023-02134-4 |
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