Polymeric glabrescione B nanocapsules for passive targeting of Hedgehog-dependent tumor therapy

TY - JOUR

T1 - Polymeric glabrescione B nanocapsules for passive targeting of Hedgehog-dependent tumor therapy

AU - Ingallina, Cinzia

AU - Costa, Pedro M.

AU - Ghirga, Francesca

AU - Klippstein, Rebecca

AU - Wang, Julie T.

AU - Berardozzi, Simone

AU - Hodgins, Naomi

AU - Infante, Paola

AU - Pollard, Steven M.

AU - Botta, Bruno

AU - Al-Jamal, Khuloud T.

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Aim: With the purpose of delivering high doses of glabrescione B (GlaB) to solid tumors after systemic administration, long-circulating GlaB-loaded oil-cored polymeric nanocapsules (NC-GlaB) were formulated. Materials & methods: Synthesis of GlaB and its encapsulation in nanocapsules (NCs) was performed. Empty and GlaB-loaded NCs were assessed for their physico-chemical properties, in vitro cytotoxicity and in vivo biodistribution. Results: GlaB was efficiently loaded into NCs (90%), which were small (160 nm), homogeneous and stable upon storage. Further, GlaB and NC-GlaB demonstrated specific activities against the cancer stem cells. Preliminary studies in tumor-bearing mice supported the ability of NC to accumulate in pancreatic tumors. Conclusion: This study provides early evidence that NC-GlaB has the potential to be utilized in a preclinical setting and justifies the need to perform therapeutic experiments in mice.

AB - Aim: With the purpose of delivering high doses of glabrescione B (GlaB) to solid tumors after systemic administration, long-circulating GlaB-loaded oil-cored polymeric nanocapsules (NC-GlaB) were formulated. Materials & methods: Synthesis of GlaB and its encapsulation in nanocapsules (NCs) was performed. Empty and GlaB-loaded NCs were assessed for their physico-chemical properties, in vitro cytotoxicity and in vivo biodistribution. Results: GlaB was efficiently loaded into NCs (90%), which were small (160 nm), homogeneous and stable upon storage. Further, GlaB and NC-GlaB demonstrated specific activities against the cancer stem cells. Preliminary studies in tumor-bearing mice supported the ability of NC to accumulate in pancreatic tumors. Conclusion: This study provides early evidence that NC-GlaB has the potential to be utilized in a preclinical setting and justifies the need to perform therapeutic experiments in mice.

KW - glabrescione B (GlaB)

KW - Hedgehog (Hh) pathway

KW - oil-cored polymeric nanocapsules

UR - http://www.scopus.com/inward/record.url?scp=85016410326&partnerID=8YFLogxK

U2 - 10.2217/nnm-2016-0388

DO - 10.2217/nnm-2016-0388

M3 - Article

AN - SCOPUS:85016410326

SN - 1743-5889

VL - 12

SP - 711

EP - 728

JO - Nanomedicine

JF - Nanomedicine

IS - 7

ER -