乳腺癌（BC）是女性中最常诊断出的癌症。化疗、免疫和光热疗法可用于治疗 BC。然而，肿瘤微环境（TME）阻止游离药物和纳米载体（NC）进入肿瘤场所。配方科学家依靠增强渗透和保留 (EPR) 来使 TME 中的 NC 外渗。然而，最近的研究表明，不同患者和肿瘤类型之间的 EPR 性质不一致。此外，血管生成、高肿瘤内流体压力、结缔组织增生以及高细胞和细胞外基质密度阻碍了 TME 中 NC 的积累。在这篇综述中，我们讨论 TME 正常化作为提高药物和 NCS 在肿瘤场所渗透的方法。本手稿讨论了肿瘤血管正常化、逆转缺氧、缓解高瘤内压以及淋巴细胞浸润以逆转治疗失败等策略。讨论了血管正常化后促进 TME 中抗癌免疫细胞浸润的策略。重点介绍了制定 TME 正常化药物给药时间点的研究。控制血管生成和正常化过程的机制途径与研究一起进行了讨论。该综述将为制剂科学家提供更深入的肿瘤靶向见解。© 2024。控释协会。

Breast cancer (BC) is the most commonly diagnosed cancer among women. Chemo-, immune- and photothermal therapies are employed to manage BC. However, the tumor microenvironment (TME) prevents free drugs and nanocarriers (NCs) from entering the tumor premises. Formulation scientists rely on enhanced permeation and retention (EPR) to extravasate NCs in the TME. However, recent research has demonstrated the inconsistent nature of EPR among different patients and tumor types. In addition, angiogenesis, high intra-tumor fluid pressure, desmoplasia, and high cell and extracellular matrix density resist the accumulation of NCs in the TME. In this review, we discuss TME normalization as an approach to improve the penetration of drugs and NCSs in the tumor premises. Strategies such as normalization of tumor vessels, reversal of hypoxia, alleviation of high intra-tumor pressure, and infiltration of lymphocytes for the reversal of therapy failure have been discussed in this manuscript. Strategies to promote the infiltration of anticancer immune cells in the TME after vascular normalization have been discussed. Studies strategizing time points to administer TME-normalizing agents are highlighted. Mechanistic pathways controlling the angiogenesis and normalization processes are discussed along with the studies. This review will provide greater tumor-targeting insights to the formulation scientists.© 2024. Controlled Release Society.