Polymeric Nanoparticles Simultaneously Delivering Paclitaxel Prodrug and Combretastatin A4 with Exceptionally High Drug Loading for Cancer Combination Therapy

IF 9.1 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Letters Pub Date : 2025-02-24 DOI:10.1021/acs.nanolett.4c05863

Huicong Zhou, Zhaofan Yang, Guanyu Jin, Lanqing Wang, Yuanzhen Su, Hao Liu, Hai Sun, Lingwei Xue, Liwei Mi, Irina A. Veselova, Mingqiang Li, Shixian Lv, Xuesi Chen

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引用次数: 0

Abstract

Nanomedicines capable of delivering multiple drugs have become essential in combination therapy. However, the challenges of low drug loading capacity (DLC) and difficulties in administering dosages between different drugs significantly limit the antitumor efficacy. In this study, a nanomedicine constructed through a rational prodrug and nanocarrier design was reported for cancer combination therapy. Initially, a phenylborate ester (PBE) group-modified paclitaxel (PTX) prodrug (PTX–PBE) was synthesized and could self-assemble in water. Subsequently, combretastatin A4 (CA4) polymer conjugates, mPEG–PCA4 (PCA4), were synthesized as nanocarriers to facilitate the exceptionally high drug loading of PTX–PBE in a precisely controlled manner. Both the in vitro and in vivo experiments demonstrated that the PCA4 loading PTX–PBE nanoparticles (PCA4/PTX–PBE NPs) exhibited potent antitumor efficacy and favorable biocompatibility. Our approach provides a straightforward, efficient, and controllable strategy for the co-delivery of pharmaceuticals in clinical cancer combination therapy.

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聚合纳米颗粒同时递送紫杉醇前药和康布他汀A4，具有极高的药物负荷，用于癌症联合治疗

能够提供多种药物的纳米药物在联合治疗中已经成为必不可少的。然而，低载药能力（DLC）和不同药物之间给药困难的挑战显着限制了抗肿瘤效果。本研究通过合理的前药和纳米载体设计构建了一种用于肿瘤联合治疗的纳米药物。首先，合成了一种苯基硼酸酯（PBE）基团修饰的紫杉醇（PTX）前药（PTX - PBE），并能在水中自组装。随后，合成了combretastatin A4 （CA4）聚合物偶联物mPEG-PCA4 （PCA4）作为纳米载体，以精确控制的方式促进PTX-PBE的高载药。体外和体内实验均表明，PCA4负载PTX-PBE纳米颗粒（PCA4/ PTX-PBE NPs）具有强大的抗肿瘤功效和良好的生物相容性。我们的方法为临床癌症联合治疗中药物的共同递送提供了一种简单、有效和可控的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nano Letters 工程技术-材料科学：综合

CiteScore

16.80

自引率

2.80%

发文量

1182

审稿时长

1.4 months

期刊介绍： Nano Letters serves as a dynamic platform for promptly disseminating original results in fundamental, applied, and emerging research across all facets of nanoscience and nanotechnology. A pivotal criterion for inclusion within Nano Letters is the convergence of at least two different areas or disciplines, ensuring a rich interdisciplinary scope. The journal is dedicated to fostering exploration in diverse areas, including: - Experimental and theoretical findings on physical, chemical, and biological phenomena at the nanoscale - Synthesis, characterization, and processing of organic, inorganic, polymer, and hybrid nanomaterials through physical, chemical, and biological methodologies - Modeling and simulation of synthetic, assembly, and interaction processes - Realization of integrated nanostructures and nano-engineered devices exhibiting advanced performance - Applications of nanoscale materials in living and environmental systems Nano Letters is committed to advancing and showcasing groundbreaking research that intersects various domains, fostering innovation and collaboration in the ever-evolving field of nanoscience and nanotechnology.