Enhancement of Tumor Homing by Chemotherapy-Loaded Nanoparticles

Mirco Ponzoni, Flavio Curnis, Chiara Brignole, Silvia Bruno, Daniela Guarnieri, Leopoldo Sitia, Roberto Marotta, Angelina Sacchi, Matteo Bauckneht, Ambra Buschiazzo, Andrea Rossi, Daniela Di Paolo, Patrizia Perri, Alessandro Gori, Angela R Sementa, Laura Emionite, Michele Cilli, Roberto Tamma, Domenico Ribatti, Pier Paolo PompaCecilia Marini, Gianmario Sambuceti, Angelo Corti, Fabio Pastorino

Research output: Contribution to journalArticle

Abstract

Targeted delivery of anticancer drugs with nanocarriers can reduce side effects and ameliorate therapeutic efficacy. However, poorly perfused and dysfunctional tumor vessels limit the transport of the payload into solid tumors. The use of tumor-penetrating nanocarriers might enhance tumor uptake and antitumor effects. A peptide containing a tissue-penetrating (TP) consensus motif, capable of recognizing neuropilin-1, is here fused to a neuroblastoma-targeting peptide (pep) previously developed. Neuroblastoma cell lines and cells derived from both xenografts and high-risk neuroblastoma patients show overexpression of neuropilin-1. In vitro studies reveal that TP-pep binds cell lines and cells derived from neuroblastoma patients more efficiently than pep. TP-pep, after coupling to doxorubicin-containing stealth liposomes (TP-pep-SL[doxorubicin]), enhances their uptake by cells and cytotoxic effects in vitro, while increasing tumor-binding capability and homing in vivo. TP-pep-SL[doxorubicin] treatment enhances the Evans Blue dye accumulation in tumors but not in nontumor tissues, pointing to selective increase of vascular permeability in tumor tissues. Compared to pep-SL[doxorubicin], TP-pep-SL[doxorubicin] shows an increased antineuroblastoma activity in three neuroblastoma animal models mimicking the growth of neuroblastoma in humans. The enhancement of drug penetration in tumors by TP-pep-targeted nanoparticles may represent an innovative strategy for neuroblastoma.

Original languageEnglish
Pages (from-to)e1802886
JournalSmall
Volume14
Issue number45
DOIs
Publication statusPublished - Nov 2018

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Chemotherapy
Nanoparticles
Peptides
Tumors
Tissue
Neuroblastoma
Drug Therapy
Doxorubicin
Neoplasms
Neuropilin-1
Cell-Penetrating Peptides
Cells
Evans Blue
Cell Line
Liposomes
Capillary Permeability
Heterografts
Therapeutic Uses
Pharmaceutical Preparations
Animals

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Enhancement of Tumor Homing by Chemotherapy-Loaded Nanoparticles. / Ponzoni, Mirco; Curnis, Flavio; Brignole, Chiara; Bruno, Silvia; Guarnieri, Daniela; Sitia, Leopoldo; Marotta, Roberto; Sacchi, Angelina; Bauckneht, Matteo; Buschiazzo, Ambra; Rossi, Andrea; Di Paolo, Daniela; Perri, Patrizia; Gori, Alessandro; Sementa, Angela R; Emionite, Laura; Cilli, Michele; Tamma, Roberto; Ribatti, Domenico; Pompa, Pier Paolo; Marini, Cecilia; Sambuceti, Gianmario; Corti, Angelo; Pastorino, Fabio.

In: Small, Vol. 14, No. 45, 11.2018, p. e1802886.

Research output: Contribution to journalArticle

Ponzoni, M, Curnis, F, Brignole, C, Bruno, S, Guarnieri, D, Sitia, L, Marotta, R, Sacchi, A, Bauckneht, M, Buschiazzo, A, Rossi, A, Di Paolo, D, Perri, P, Gori, A, Sementa, AR, Emionite, L, Cilli, M, Tamma, R, Ribatti, D, Pompa, PP, Marini, C, Sambuceti, G, Corti, A & Pastorino, F 2018, 'Enhancement of Tumor Homing by Chemotherapy-Loaded Nanoparticles', Small, vol. 14, no. 45, pp. e1802886. https://doi.org/10.1002/smll.201802886
Ponzoni, Mirco ; Curnis, Flavio ; Brignole, Chiara ; Bruno, Silvia ; Guarnieri, Daniela ; Sitia, Leopoldo ; Marotta, Roberto ; Sacchi, Angelina ; Bauckneht, Matteo ; Buschiazzo, Ambra ; Rossi, Andrea ; Di Paolo, Daniela ; Perri, Patrizia ; Gori, Alessandro ; Sementa, Angela R ; Emionite, Laura ; Cilli, Michele ; Tamma, Roberto ; Ribatti, Domenico ; Pompa, Pier Paolo ; Marini, Cecilia ; Sambuceti, Gianmario ; Corti, Angelo ; Pastorino, Fabio. / Enhancement of Tumor Homing by Chemotherapy-Loaded Nanoparticles. In: Small. 2018 ; Vol. 14, No. 45. pp. e1802886.
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AU - Ponzoni, Mirco

AU - Curnis, Flavio

AU - Brignole, Chiara

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AU - Guarnieri, Daniela

AU - Sitia, Leopoldo

AU - Marotta, Roberto

AU - Sacchi, Angelina

AU - Bauckneht, Matteo

AU - Buschiazzo, Ambra

AU - Rossi, Andrea

AU - Di Paolo, Daniela

AU - Perri, Patrizia

AU - Gori, Alessandro

AU - Sementa, Angela R

AU - Emionite, Laura

AU - Cilli, Michele

AU - Tamma, Roberto

AU - Ribatti, Domenico

AU - Pompa, Pier Paolo

AU - Marini, Cecilia

AU - Sambuceti, Gianmario

AU - Corti, Angelo

AU - Pastorino, Fabio

N1 - © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PY - 2018/11

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N2 - Targeted delivery of anticancer drugs with nanocarriers can reduce side effects and ameliorate therapeutic efficacy. However, poorly perfused and dysfunctional tumor vessels limit the transport of the payload into solid tumors. The use of tumor-penetrating nanocarriers might enhance tumor uptake and antitumor effects. A peptide containing a tissue-penetrating (TP) consensus motif, capable of recognizing neuropilin-1, is here fused to a neuroblastoma-targeting peptide (pep) previously developed. Neuroblastoma cell lines and cells derived from both xenografts and high-risk neuroblastoma patients show overexpression of neuropilin-1. In vitro studies reveal that TP-pep binds cell lines and cells derived from neuroblastoma patients more efficiently than pep. TP-pep, after coupling to doxorubicin-containing stealth liposomes (TP-pep-SL[doxorubicin]), enhances their uptake by cells and cytotoxic effects in vitro, while increasing tumor-binding capability and homing in vivo. TP-pep-SL[doxorubicin] treatment enhances the Evans Blue dye accumulation in tumors but not in nontumor tissues, pointing to selective increase of vascular permeability in tumor tissues. Compared to pep-SL[doxorubicin], TP-pep-SL[doxorubicin] shows an increased antineuroblastoma activity in three neuroblastoma animal models mimicking the growth of neuroblastoma in humans. The enhancement of drug penetration in tumors by TP-pep-targeted nanoparticles may represent an innovative strategy for neuroblastoma.

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