Enhancement of Tumor Homing by Chemotherapy-Loaded Nanoparticles

M Ponzoni, F Curnis, C Brignole, S Bruno, Daniela Guarnieri, L Sitia, Roberto Marotta, A Sacchi, M Bauckneht, A Buschiazzo, A Rossi, D Di Paolo, P Perri, A Gori, AR Sementa, L Emionite, M Cilli, R Tamma, D Ribatti, PP PompaC Marini, G Sambuceti, A Corti, F 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. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Original languageEnglish
Article number1802886
JournalSmall
Volume14
Issue number45
DOIs
Publication statusPublished - 2018

Fingerprint

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

Cite this

Ponzoni, M., Curnis, F., Brignole, C., Bruno, S., Guarnieri, D., Sitia, L., ... Pastorino, F. (2018). Enhancement of Tumor Homing by Chemotherapy-Loaded Nanoparticles. Small, 14(45), [1802886]. https://doi.org/10.1002/smll.201802886

Enhancement of Tumor Homing by Chemotherapy-Loaded Nanoparticles. / Ponzoni, M; Curnis, F; Brignole, C; Bruno, S; Guarnieri, Daniela; Sitia, L; Marotta, Roberto; 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.

In: Small, Vol. 14, No. 45, 1802886, 2018.

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, 1802886. https://doi.org/10.1002/smll.201802886
Ponzoni M, Curnis F, Brignole C, Bruno S, Guarnieri D, Sitia L et al. Enhancement of Tumor Homing by Chemotherapy-Loaded Nanoparticles. Small. 2018;14(45). 1802886. https://doi.org/10.1002/smll.201802886
Ponzoni, M ; Curnis, F ; Brignole, C ; Bruno, S ; Guarnieri, Daniela ; Sitia, L ; Marotta, Roberto ; 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. / Enhancement of Tumor Homing by Chemotherapy-Loaded Nanoparticles. In: Small. 2018 ; Vol. 14, No. 45.
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AU - Curnis, F

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AU - Sitia, L

AU - Marotta, Roberto

AU - Sacchi, A

AU - Bauckneht, M

AU - Buschiazzo, A

AU - Rossi, A

AU - Di Paolo, D

AU - Perri, P

AU - Gori, A

AU - Sementa, AR

AU - Emionite, L

AU - Cilli, M

AU - Tamma, R

AU - Ribatti, D

AU - Pompa, PP

AU - Marini, C

AU - Sambuceti, G

AU - Corti, A

AU - Pastorino, F

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

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