Two-in-one nanoparticle platform induces a strong therapeutic effect of targeted therapies in P-selectin–expressing cancers
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.
Authors
- Sabina Pozzi (ORCID: https://orcid.org/0000-0002-6299-9273)
- Marina Green Buzhor (ORCID: https://orcid.org/0009-0001-7913-3513)
- Anna Scomparin (ORCID: https://orcid.org/0000-0003-4751-620X)
- Rachel Blau (ORCID: https://orcid.org/0000-0002-1285-8894)
- Shlomi Lazar
- Gal Shenbach‐Koltin
- Yana Epshtein
- Laura Woythe (ORCID: https://orcid.org/0000-0002-3125-130X)
- Pradip Dey (ORCID: https://orcid.org/0000-0002-1302-0874)
- Shahar Tevet (ORCID: https://orcid.org/0000-0002-7614-6159)
- Ronit Satchi‐Fainaro (ORCID: https://orcid.org/0000-0002-7360-7837)
- Lorenzo Albertazzi (ORCID: https://orcid.org/0000-0002-6837-0812)
- Roey J. Amir (ORCID: https://orcid.org/0000-0002-8502-3302)
- Daniel Rodriguez Ajamil (ORCID: https://orcid.org/0000-0003-1154-695X)
- Eilam Yeini (ORCID: https://orcid.org/0000-0003-3491-3994)
- Shani Koshrovski‐Michael (ORCID: https://orcid.org/0000-0002-1985-479X)
- Iris Barshack (ORCID: https://orcid.org/0000-0001-8216-8963)
- Helena F. Florindo (ORCID: https://orcid.org/0000-0002-4006-5840)
- Ron Kleiner (ORCID: https://orcid.org/0000-0002-4638-4738)
- Rami Khoury
Institutions
- Israel Institute for Biological Research (IL)
- Visva-Bharati University (IN)
- University of Lisbon (PT)
- Tel Aviv University (IL)
- Sheba Medical Center (IL)
- University of Turin (IT)
- Eindhoven University of Technology (NL)
Publication Details
- Journal
- Science Advances
- Published
- 2024-12-13
- DOI
- https://doi.org/10.1126/sciadv.adr4762
- Citations
- 8
- Primary Topic
- Cell Adhesion Molecules Research
- Type
- article
- Field-Weighted Citation Impact
- 3.06