Abstract | BACKGROUND: RESULTS: In vitro biochemical studies showed that both nanodrugs were monodispersed and functional in terms of binding to TNF and IL12 receptors and to αvβ3. In vivo studies performed in a murine model of fibrosarcoma showed that low doses of bifunctional nanoparticles bearing isoDGR and TNF (corresponding to few nanoparticles per cell) delayed tumor growth and increased the efficacy of doxorubicin without worsening its toxicity. Similar effects were obtained using trifunctional nanoparticles loaded with isoDGR, TNF and IL12. Mechanistic studies showed that nanoparticles bearing isoDGR and TNF could increase doxorubicin penetration in tumors a few hours after injection and caused vascular damage at later time points. CONCLUSION: IsoDGR-coated gold nanospheres can be exploited as a versatile platform for single- or multi- cytokine delivery to cells of the tumor vasculature. Extremely low doses of isoDGR-coated nanodrugs functionalized with TNF or TNF plus IL12 can enhance doxorubicin anti- tumor activity.
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Authors | Angelo Corti, Angelina Sacchi, Anna Maria Gasparri, Matteo Monieri, Giulia Anderluzzi, Barbara Colombo, Alessandro Gori, Anna Mondino, Flavio Curnis |
Journal | Journal of nanobiotechnology
(J Nanobiotechnology)
Vol. 19
Issue 1
Pg. 128
(May 05 2021)
ISSN: 1477-3155 [Electronic] England |
PMID | 33952242
(Publication Type: Journal Article)
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Chemical References |
- Antineoplastic Agents
- Cytokines
- Integrin alphaVbeta3
- Tumor Necrosis Factor-alpha
- Interleukin-12
- Doxorubicin
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Topics |
- Animals
- Antineoplastic Agents
(pharmacology)
- Cell Line, Tumor
- Cytokines
- Doxorubicin
(pharmacology)
- Drug Delivery Systems
- Humans
- Integrin alphaVbeta3
- Interleukin-12
- Mice
- Mice, Inbred BALB C
- Nanostructures
(chemistry, therapeutic use)
- Tumor Necrosis Factor-alpha
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