Abstract
Selective tumor targeting is expected to enhance drug delivery and to decrease toxicity, resulting in an improved therapeutic index. We have recently identified the HSYWLRS peptide sequence as a specific ligand for aggressive neuroblastoma, a childhood tumor mostly refractory to current therapies. Here we validated the specific binding of HSYWLRS to neuroblastoma cell suspensions obtained either from cell lines, animal models, or Schwannian-stroma poor, stage IV neuroblastoma patients. Binding of the biotinylated peptide and of HSYWLRS-functionalized fluorescent quantum dots or liposomal nanoparticles was dose-dependent and inhibited by an excess of free peptide. In animal models obtained by the orthotopic implant of either MYCN-amplified or MYCN single copy human neuroblastoma cell lines, treatment with HSYWLRS-targeted, doxorubicin-loaded Stealth Liposomes increased tumor vascular permeability and perfusion, enhancing tumor penetration of the drug. This formulation proved to exert a potent antitumor efficacy, as evaluated by bioluminescence imaging and micro-PET, leading to (i) delay of tumor growth paralleled by decreased tumor glucose consumption, and (ii) abrogation of metastatic spreading, accompanied by absence of systemic toxicity and significant increase in the animal life span. Our findings are functional to the design of targeted nanocarriers with potentiated therapeutic efficacy towards the clinical translation.
| Original language | English |
|---|---|
| Pages (from-to) | 89-99 |
| Number of pages | 11 |
| Journal | Biomaterials |
| Volume | 68 |
| DOIs | |
| Publication status | Published - Nov 1 2015 |
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Keywords
- Drug delivery
- Micro-PET
- Neuroblastoma
- Targeted therapy
- Tumor penetration
ASJC Scopus subject areas
- Biomaterials
- Bioengineering
- Ceramics and Composites
- Mechanics of Materials
- Biophysics
Cite this
Neuroblastoma-targeted nanocarriers improve drug delivery and penetration, delay tumor growth and abrogate metastatic diffusion. / Cossu, Irene; Bottoni, Gianluca; Loi, Monica; Emionite, Laura; Bartolini, Alice; Di Paolo, Daniela; Brignole, Chiara; Piaggio, Francesca; Perri, Patrizia; Sacchi, Angelina; Curnis, Flavio; Gagliani, Maria Cristina; Bruno, Silvia; Marini, Cecilia; Gori, Alessandro; Longhi, Renato; Murgia, Daniele; Sementa, Angela Rita; Cilli, Michele; Tacchetti, Carlo; Corti, Angelo; Sambuceti, Gianmario; Marchiò, Serena; Ponzoni, Mirco; Pastorino, Fabio.
In: Biomaterials, Vol. 68, 01.11.2015, p. 89-99.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Neuroblastoma-targeted nanocarriers improve drug delivery and penetration, delay tumor growth and abrogate metastatic diffusion
AU - Cossu, Irene
AU - Bottoni, Gianluca
AU - Loi, Monica
AU - Emionite, Laura
AU - Bartolini, Alice
AU - Di Paolo, Daniela
AU - Brignole, Chiara
AU - Piaggio, Francesca
AU - Perri, Patrizia
AU - Sacchi, Angelina
AU - Curnis, Flavio
AU - Gagliani, Maria Cristina
AU - Bruno, Silvia
AU - Marini, Cecilia
AU - Gori, Alessandro
AU - Longhi, Renato
AU - Murgia, Daniele
AU - Sementa, Angela Rita
AU - Cilli, Michele
AU - Tacchetti, Carlo
AU - Corti, Angelo
AU - Sambuceti, Gianmario
AU - Marchiò, Serena
AU - Ponzoni, Mirco
AU - Pastorino, Fabio
PY - 2015/11/1
Y1 - 2015/11/1
N2 - Selective tumor targeting is expected to enhance drug delivery and to decrease toxicity, resulting in an improved therapeutic index. We have recently identified the HSYWLRS peptide sequence as a specific ligand for aggressive neuroblastoma, a childhood tumor mostly refractory to current therapies. Here we validated the specific binding of HSYWLRS to neuroblastoma cell suspensions obtained either from cell lines, animal models, or Schwannian-stroma poor, stage IV neuroblastoma patients. Binding of the biotinylated peptide and of HSYWLRS-functionalized fluorescent quantum dots or liposomal nanoparticles was dose-dependent and inhibited by an excess of free peptide. In animal models obtained by the orthotopic implant of either MYCN-amplified or MYCN single copy human neuroblastoma cell lines, treatment with HSYWLRS-targeted, doxorubicin-loaded Stealth Liposomes increased tumor vascular permeability and perfusion, enhancing tumor penetration of the drug. This formulation proved to exert a potent antitumor efficacy, as evaluated by bioluminescence imaging and micro-PET, leading to (i) delay of tumor growth paralleled by decreased tumor glucose consumption, and (ii) abrogation of metastatic spreading, accompanied by absence of systemic toxicity and significant increase in the animal life span. Our findings are functional to the design of targeted nanocarriers with potentiated therapeutic efficacy towards the clinical translation.
AB - Selective tumor targeting is expected to enhance drug delivery and to decrease toxicity, resulting in an improved therapeutic index. We have recently identified the HSYWLRS peptide sequence as a specific ligand for aggressive neuroblastoma, a childhood tumor mostly refractory to current therapies. Here we validated the specific binding of HSYWLRS to neuroblastoma cell suspensions obtained either from cell lines, animal models, or Schwannian-stroma poor, stage IV neuroblastoma patients. Binding of the biotinylated peptide and of HSYWLRS-functionalized fluorescent quantum dots or liposomal nanoparticles was dose-dependent and inhibited by an excess of free peptide. In animal models obtained by the orthotopic implant of either MYCN-amplified or MYCN single copy human neuroblastoma cell lines, treatment with HSYWLRS-targeted, doxorubicin-loaded Stealth Liposomes increased tumor vascular permeability and perfusion, enhancing tumor penetration of the drug. This formulation proved to exert a potent antitumor efficacy, as evaluated by bioluminescence imaging and micro-PET, leading to (i) delay of tumor growth paralleled by decreased tumor glucose consumption, and (ii) abrogation of metastatic spreading, accompanied by absence of systemic toxicity and significant increase in the animal life span. Our findings are functional to the design of targeted nanocarriers with potentiated therapeutic efficacy towards the clinical translation.
KW - Drug delivery
KW - Micro-PET
KW - Neuroblastoma
KW - Targeted therapy
KW - Tumor penetration
UR - http://www.scopus.com/inward/record.url?scp=84939637159&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84939637159&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2015.07.054
DO - 10.1016/j.biomaterials.2015.07.054
M3 - Article
C2 - 26276694
AN - SCOPUS:84939637159
VL - 68
SP - 89
EP - 99
JO - Biomaterials
JF - Biomaterials
SN - 0142-9612
ER -