TY - JOUR
T1 - Two-in-one nanoparticle platform induces a strong therapeutic effect of targeted therapies in P-selectin-expressing cancers
AU - Koshrovski-Michael, Shani
AU - Ajamil, Daniel Rodriguez
AU - Dey, Pradip
AU - Kleiner, Ron
AU - Tevet, Shahar
AU - Epshtein, Yana
AU - Buzhor, Marina Green
AU - Khoury, Rami
AU - Pozzi, Sabina
AU - Shenbach-Koltin, Gal
AU - Yeini, Eilam
AU - Woythe, Laura
AU - Blau, Rachel
AU - Scomparin, Anna
AU - Barshack, Iris
AU - Florindo, Helena F.
AU - Lazar, Shlomi
AU - Albertazzi, Lorenzo
AU - Amir, Roey J.
AU - Satchi-Fainaro, Ronit
N1 - Publisher Copyright:
© 2024 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
PY - 2024/12/13
Y1 - 2024/12/13
N2 - Combined therapies in cancer treatment aim to enhance antitumor activity. However, delivering multiple small molecules imposes challenges, as different drugs have distinct pharmacokinetic profiles and tumor penetration abilities, affecting their therapeutic efficacy. To circumvent this, poly(lactic-co- glycolic acid) (PLGA)-polyethylene glycol (PEG)-based nanoparticles were developed as a platform for the codelivery of synergistic drug ratios, improving therapeutic efficacy by increasing the percentage of injected dose reaching the tumor. Nonetheless, extravasation-dependent tumor accumulation is susceptible to variations in tumor vasculature; therefore, PLGA-PEG was modified with sulfates to actively target P-selectin- expressing cancers. Here, we show the potential of our platform in unique three-dimensional (3D) in vitro and in vivo models. The P-selectin- targeted nanoparticles showed enhanced accumulation in 3D spheroids and tissues of P-selectin- expressing BRAF-mutated melanomas and BRCA-mutated breast cancers, resulting in superior in vivo efficacy and safety. This nanoplatform could advance the codelivery of a plethora of anticancer drug combinations to various P-selectin- expressing tumors.
AB - Combined therapies in cancer treatment aim to enhance antitumor activity. However, delivering multiple small molecules imposes challenges, as different drugs have distinct pharmacokinetic profiles and tumor penetration abilities, affecting their therapeutic efficacy. To circumvent this, poly(lactic-co- glycolic acid) (PLGA)-polyethylene glycol (PEG)-based nanoparticles were developed as a platform for the codelivery of synergistic drug ratios, improving therapeutic efficacy by increasing the percentage of injected dose reaching the tumor. Nonetheless, extravasation-dependent tumor accumulation is susceptible to variations in tumor vasculature; therefore, PLGA-PEG was modified with sulfates to actively target P-selectin- expressing cancers. Here, we show the potential of our platform in unique three-dimensional (3D) in vitro and in vivo models. The P-selectin- targeted nanoparticles showed enhanced accumulation in 3D spheroids and tissues of P-selectin- expressing BRAF-mutated melanomas and BRCA-mutated breast cancers, resulting in superior in vivo efficacy and safety. This nanoplatform could advance the codelivery of a plethora of anticancer drug combinations to various P-selectin- expressing tumors.
UR - https://www.scopus.com/pages/publications/85212594677
U2 - 10.1126/sciadv.adr4762
DO - 10.1126/sciadv.adr4762
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C2 - 39671487
AN - SCOPUS:85212594677
SN - 2375-2548
VL - 10
JO - Science advances
JF - Science advances
IS - 50
M1 - eadr4762
ER -
