n the attempt to develop novel concepts in designing targeted nanoparticles for combination therapy of cancer, we propose here CD44-targeted hyaluronan-decorated double-coated nanoparticles (dcNPs) delivering the lipophilic chemotherapeutic docetaxel (DTX) and an anionic porphyrin (TPPS₄). dcNPs are based on electrostatic interactions between a negative DTX-loaded nanoscaffold of poly(lactide-co-glycolide), a polycationic shell of polyethyleneimine entangling negatively-charged TPPS₄ and finally decorated with hyaluronan (HA) to promote internalization through CD44 receptor-mediated endocytosis. DTX/TPPS₄-dcNPs, prepared through layer-by-layer deposition, showed a hydrodynamic diameter of around 180 nm, negative zeta potential and efficient loading of both DTX and TPPS₄. DTX/TPPS₄-dcNPs were freeze-dried with trehalose giving a powder that could be easily dispersed in different media. Excellent stability of dcNPs in specific salt- and protein-containing media was found. Spectroscopic behavior of DTX/TPPS₄-dcNPs demonstrated a face-to-face arrangement of the TPPS₄ units in non-photoresponsive H-type aggregates accounting for an extensive aggregation of the porphyrin embedded in the shell. Experiments in MDA-MB-231 cells overexpressing the CD44 receptor demonstrated a 9.4-fold increase in the intracellular level of TPPS₄ delivered from dcNPs as compared to free TPPS₄. Light-induced death increased tremendously in cells that had been treated with a combination of TPPS₄ and DTX delivered through dcNPs as compared with free drugs, presumably due to efficient uptake and co-localization inside the cells. In perspective, the strategy proposed here to target synergistic drug combinations through HA-decorated nanoparticles seems very attractive to improve the specificity and efficacy of cancer treatment.

Hyaluronan-decorated polymer nanoparticles targeting the CD44 receptor for the combined photo/chemo-therapy of cancer / Maiolino, Sara; Moret, F; Conte, Claudia; Fraix, A; Tirino, P; Ungaro, Francesca; Sortino, S; Reddi, E; Quaglia, Fabiana. - In: NANOSCALE. - ISSN 2040-3364. - 7:13(2015), pp. 5643-5653. [10.1039/c4nr06910b]

Hyaluronan-decorated polymer nanoparticles targeting the CD44 receptor for the combined photo/chemo-therapy of cancer.

MAIOLINO, SARA;CONTE, CLAUDIA;UNGARO, FRANCESCA;QUAGLIA, FABIANA
Ultimo
Conceptualization
2015

Abstract

n the attempt to develop novel concepts in designing targeted nanoparticles for combination therapy of cancer, we propose here CD44-targeted hyaluronan-decorated double-coated nanoparticles (dcNPs) delivering the lipophilic chemotherapeutic docetaxel (DTX) and an anionic porphyrin (TPPS₄). dcNPs are based on electrostatic interactions between a negative DTX-loaded nanoscaffold of poly(lactide-co-glycolide), a polycationic shell of polyethyleneimine entangling negatively-charged TPPS₄ and finally decorated with hyaluronan (HA) to promote internalization through CD44 receptor-mediated endocytosis. DTX/TPPS₄-dcNPs, prepared through layer-by-layer deposition, showed a hydrodynamic diameter of around 180 nm, negative zeta potential and efficient loading of both DTX and TPPS₄. DTX/TPPS₄-dcNPs were freeze-dried with trehalose giving a powder that could be easily dispersed in different media. Excellent stability of dcNPs in specific salt- and protein-containing media was found. Spectroscopic behavior of DTX/TPPS₄-dcNPs demonstrated a face-to-face arrangement of the TPPS₄ units in non-photoresponsive H-type aggregates accounting for an extensive aggregation of the porphyrin embedded in the shell. Experiments in MDA-MB-231 cells overexpressing the CD44 receptor demonstrated a 9.4-fold increase in the intracellular level of TPPS₄ delivered from dcNPs as compared to free TPPS₄. Light-induced death increased tremendously in cells that had been treated with a combination of TPPS₄ and DTX delivered through dcNPs as compared with free drugs, presumably due to efficient uptake and co-localization inside the cells. In perspective, the strategy proposed here to target synergistic drug combinations through HA-decorated nanoparticles seems very attractive to improve the specificity and efficacy of cancer treatment.
2015
Hyaluronan-decorated polymer nanoparticles targeting the CD44 receptor for the combined photo/chemo-therapy of cancer / Maiolino, Sara; Moret, F; Conte, Claudia; Fraix, A; Tirino, P; Ungaro, Francesca; Sortino, S; Reddi, E; Quaglia, Fabiana. - In: NANOSCALE. - ISSN 2040-3364. - 7:13(2015), pp. 5643-5653. [10.1039/c4nr06910b]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/611272
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 66
  • ???jsp.display-item.citation.isi??? 65
social impact