Two-in-one nanoparticle platform induces a strong therapeutic effect of targeted therapies in P-selectin–expressing cancers

IF 11.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Science Advances Pub Date : 2024-12-13 DOI:10.1126/sciadv.adr4762
Shani Koshrovski-Michael, Daniel Rodriguez Ajamil, Pradip Dey, Ron Kleiner, Shahar Tevet, Yana Epshtein, Marina Green Buzhor, Rami Khoury, Sabina Pozzi, Gal Shenbach-Koltin, Eilam Yeini, Laura Woythe, Rachel Blau, Anna Scomparin, Iris Barshack, Helena F. Florindo, Shlomi Lazar, Lorenzo Albertazzi, Roey J. Amir, Ronit Satchi-Fainaro
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引用次数: 0

Abstract

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.
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二合一纳米粒子平台诱导靶向疗法对表达 P 选择素的癌症产生强大疗效
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来源期刊
Science Advances
Science Advances 综合性期刊-综合性期刊
CiteScore
21.40
自引率
1.50%
发文量
1937
审稿时长
29 weeks
期刊介绍: Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.
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