Traditional methods of tumor therapy have many limitations. Thus, cancer nanomedicine is developing rapidly as a new treatment for tumors. In the past decade, the literature in this field has almost doubled every two years. However, the therapeutic nanoparticle (NP) platforms that have been approved for cancer treatment have not achieved the expected results in clinical application. Cancer nanomedicine still faces many obstacles and challenges. An abnormal cancer vascular system and a thick interstitial matrix can impose physiological barriers. As a result, drug delivery in tumor tissue depends mainly on diffusion. The diffusion efficiency of large NPs is poor; they are trapped around the blood vessels. Smallmolecule drug conjugates (SMDCs), miniaturized biologic drug conjugates (mBDCs), and small NPs can pass through this barrier. However, poor aggregation in tumors, easy elimination, and poor pharmacokinetics (PK) limit their therapeutic effects. In recent years, a selective new multistage delivery system was proposed to solve the challenge of infiltration. By incorporating smaller NPs or molecular drugs into large controlled-release particles for multistep delivery to tumors, we can make full use of the advantageous pharmacokinetics, the accumulation of large particles in the tumor, and the deep infiltration of small particles. In addition to changing the particle size, the multistage NP delivery system can also change the shape, charge, flexibility, and surface coating of the NPs to enhance penetration. Based on recent multistage delivery system research, this review expounds on the main direction of multistage delivery considering the ways in which large particles are triggered to release small particles.

中文翻译：

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多级纳米颗粒递送系统-癌症治疗的新方法。

传统的肿瘤治疗方法有很多局限性。因此，癌症纳米医学作为肿瘤的新疗法正在迅速发展。在过去的十年中，该领域的文献几乎每两年翻一番。但是，已被批准用于癌症治疗的治疗性纳米颗粒（NP）平台尚未在临床应用中获得预期的结果。癌症纳米医学仍然面临许多障碍和挑战。异常的血管系统和厚厚的间质基质会强加生理屏障。结果，肿瘤组织中的药物递送主要取决于扩散。大型NP的扩散效率很差；它们被困在血管周围。小分子药物偶联物（SMDC），小型生物药物偶联物（mBDC）和小NP都可以穿过此屏障。然而，肿瘤中不良的聚集，易于清除以及不良的药代动力学（PK）限制了它们的治疗效果。近年来，提出了一种选择性的新型多级输送系统来解决渗透的挑战。通过将较小的NPs或分子药物掺入大的控释颗粒中以分步递送至肿瘤，我们可以充分利用其有利的药代动力学，大颗粒在肿瘤中的积累以及小颗粒的深层渗透。除了更改粒径外，多级NP输送系统还可以更改NP的形状，电荷，柔韧性和表面涂层，以增强渗透性。根据最近的多阶段投放系统研究，