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

IF 11.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
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

摘要

联合治疗的目的是提高肿瘤的抗肿瘤活性。然而,由于不同的药物具有不同的药代动力学特征和穿透肿瘤的能力,从而影响其治疗效果,因此递送多个小分子药物带来了挑战。为了解决这个问题,聚乳酸-羟基乙酸(PLGA) -聚乙二醇(PEG)基纳米颗粒被开发为协同递送药物比例的平台,通过增加注射剂量到达肿瘤的百分比来提高治疗效果。尽管如此,依赖外渗的肿瘤积累容易受到肿瘤血管系统变化的影响;因此,用硫酸盐修饰PLGA-PEG以积极靶向表达p -选择素的癌症。在这里,我们在独特的三维(3D)体外和体内模型中展示了我们平台的潜力。靶向p -选择素的纳米颗粒在表达p -选择素的braf突变黑色素瘤和brca突变乳腺癌的三维球体和组织中积累增强,从而具有优越的体内疗效和安全性。这种纳米平台可以促进多种抗癌药物组合对各种表达p选择素的肿瘤的共递送。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

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.
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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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