Polymer-based nanoparticles (NPs) with a cationic charge have emerged recently as a potent nanotool due to their unique ability to penetrate deeply inside tumor tissue and to interact preferentially with the plasma membrane of cancer cells. In this paper, we propose a general strategy to obtain biodegradable cationic NPs of poly(ϵ-caprolactone) (PCL) based on an amine terminated PCL (NH2-PCL4.2k) or its mixture with monomethoxypoly(ethylene glycol)-PCL (mPEG1k-PCL4k). Positively-charged NPs were obtained, switching to net negative values through adsorption of low molecular weight hyaluronan. NPs exposing both amine and PEG groups on the surface showed a larger fixed aqueous layer thickness as compared to fully PEGylated NPs, suggesting that PEG conformation/localization is affected by the presence of amino groups. The stability of the positively-charged NPs was affected by the presence of ions, while interaction with the human plasma protein pool indicated time-dependent protein corona formation imparting an overall negative charge. NP-induced haemolysis was low, while cytotoxicity against A549 and Calu-3 lung cancer cell lines was cell-specific as well as dose and time-dependent. Finally, the presence of amino groups greatly changed the in vivo biodistribution of the NPs in tumor-bearing mice (lung colonization of B16F10 cancer cells) allowing the amine/PEGylated NPs to accumulate mainly at the target organ. Overall, this study demonstrates that NPs with a mixed amine/PEGylated surface exhibit a peculiar biological identity that alters their interaction with the bioenvironment and are thus worthy of further investigation in the delivery of chemotherapeutics.

Biodegradable nanoparticles bearing amine groups as a strategy to alter surface features, biological identity and accumulation in a lung metastasis model / Esposito, Diletta; Conte, Claudia; Dal Poggetto, Giovanni; Russo, Annapina; Barbieri, Antonio; Ungaro, Francesca; Arra, Claudio; Russo, Giulia; Laurienzo, Paola; Quaglia, Fabiana. - In: JOURNAL OF MATERIALS CHEMISTRY. B. - ISSN 2050-7518. - 6:(2018), pp. 5922-5930. [10.1039/c8tb01330f]

Biodegradable nanoparticles bearing amine groups as a strategy to alter surface features, biological identity and accumulation in a lung metastasis model

Esposito, Diletta
Primo
Investigation
;
Conte, Claudia
Secondo
Investigation
;
Russo, Annapina;Ungaro, Francesca;Russo, Giulia;Quaglia, Fabiana
Ultimo
Conceptualization
2018

Abstract

Polymer-based nanoparticles (NPs) with a cationic charge have emerged recently as a potent nanotool due to their unique ability to penetrate deeply inside tumor tissue and to interact preferentially with the plasma membrane of cancer cells. In this paper, we propose a general strategy to obtain biodegradable cationic NPs of poly(ϵ-caprolactone) (PCL) based on an amine terminated PCL (NH2-PCL4.2k) or its mixture with monomethoxypoly(ethylene glycol)-PCL (mPEG1k-PCL4k). Positively-charged NPs were obtained, switching to net negative values through adsorption of low molecular weight hyaluronan. NPs exposing both amine and PEG groups on the surface showed a larger fixed aqueous layer thickness as compared to fully PEGylated NPs, suggesting that PEG conformation/localization is affected by the presence of amino groups. The stability of the positively-charged NPs was affected by the presence of ions, while interaction with the human plasma protein pool indicated time-dependent protein corona formation imparting an overall negative charge. NP-induced haemolysis was low, while cytotoxicity against A549 and Calu-3 lung cancer cell lines was cell-specific as well as dose and time-dependent. Finally, the presence of amino groups greatly changed the in vivo biodistribution of the NPs in tumor-bearing mice (lung colonization of B16F10 cancer cells) allowing the amine/PEGylated NPs to accumulate mainly at the target organ. Overall, this study demonstrates that NPs with a mixed amine/PEGylated surface exhibit a peculiar biological identity that alters their interaction with the bioenvironment and are thus worthy of further investigation in the delivery of chemotherapeutics.
2018
Biodegradable nanoparticles bearing amine groups as a strategy to alter surface features, biological identity and accumulation in a lung metastasis model / Esposito, Diletta; Conte, Claudia; Dal Poggetto, Giovanni; Russo, Annapina; Barbieri, Antonio; Ungaro, Francesca; Arra, Claudio; Russo, Giulia; Laurienzo, Paola; Quaglia, Fabiana. - In: JOURNAL OF MATERIALS CHEMISTRY. B. - ISSN 2050-7518. - 6:(2018), pp. 5922-5930. [10.1039/c8tb01330f]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/812335
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