Abstract 3879: Enhancement of tumor penetration by drug-loaded nanoparticles: An innovative targeted strategy for neuroblastoma

Abstract

Abstract Background: Anti-cancer drugs-loaded targeted nanocarriers can reduce side-effects and improve therapeutic efficacy in preclinical studies. However, poorly perfused and dysfunctional tumour vessels limit the transport of the payload into the parenchyma of solid tumours. The use of tumour-penetrating nanocarriers might enhance tumour penetration and anti-tumour effects. Methods: A consensus motif, mediator of tissue penetration (TP) was added to a previously characterized neuroblastoma (NB)-targeting peptide (pep). In vitro NB cell association and internalization of TP-pep, either free or coupled to Stealth Liposomes (SL), were tested by FACS and confocal microscopy. In vitro cytotoxic potential of a novel doxorubicin (DXR)-loaded liposomal (TP-pep-SL[DXR]) was evaluated by MTS assay. Three mouse xenograft models mimicking the growth and spread of NB in humans (injection routes: subcutaneous; adrenal gland; tail vein) were enrolled to examine in vivo penetration, vascular permeability, tumour glucose consumption and sensitivity in response to TP-pep-SL[DXR]. Results: Compared to pep, TP-pep increases its cellular association in vitro on cell lines and cells derived from NB patients. When coupled to SL, TP-pep enhances liposomes penetration and cytotoxic effects in vitro and increases binding and penetration in a mouse model of NB. Moreover, in vivo accumulation of Evans Blue dye within the tumour mass reveals that TP-pep-SL[DXR] increases the tumour vascular permeability into NB tumour mass, but not in non-tumour tissues. Compared to pep-targeted liposomes, TP-pep-SL[DXR] leads to an increased anti-NB effect towards all the animal models tested. Conclusion: Our findings demonstrate that the enhancement of tumour penetration by drug-loaded nanoparticles might represent an innovative targeted strategy for NB. Citation Format: Mirco Ponzoni, Chiara Brignole, Laura Emionite, Silvia Bruno, Daniela Guarnieri, Leopoldo Sitia, Matteo Bauckneht, Ambra Buschiazzo, Andrea Rossi, Daniela Di Paolo, Patrizia Perri, Flavio Curnis, Alessandro Gori, Angela Rita Sementa, Michele Cilli, Pier Paolo Pompa, Gianmario Sambuceti, Angelo Corti, Fabio Pastorino. Enhancement of tumor penetration by drug-loaded nanoparticles: An innovative targeted strategy for neuroblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3879.