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 language | English |
|---|---|
| Pages (from-to) | e1802886 |
| Journal | Small |
| Volume | 14 |
| Issue number | 45 |
| DOIs | |
| Publication status | Published - Nov 2018 |
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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 journal › Article
}
TY - JOUR
T1 - Enhancement of Tumor Homing by Chemotherapy-Loaded Nanoparticles
AU - Ponzoni, Mirco
AU - Curnis, Flavio
AU - Brignole, Chiara
AU - Bruno, Silvia
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
Y1 - 2018/11
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.
AB - 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.
U2 - 10.1002/smll.201802886
DO - 10.1002/smll.201802886
M3 - Article
C2 - 30294852
VL - 14
SP - e1802886
JO - Small
JF - Small
SN - 1613-6810
IS - 45
ER -