Review

通过肿瘤血管和微环境标准化改善乳腺癌治疗：改善药物灌注和纳米载体渗透的范式转变

Amelioration of breast cancer therapies through normalization of tumor vessels and microenvironment: paradigm shift to improve drug perfusion and nanocarrier permeation

Drug Delivery and Translational Research

影响因子:5.5

分区:医学3区 / 医学：研究与实验3区药学3区

发表日期:2025 Feb

作者: Paras Famta, Saurabh Shah, Ganesh Vambhurkar, Giriraj Pandey, Deepkumar Bagasariya, Kondasingh Charan Kumar, Sajja Bhanu Prasad, Akshay Shinde, Suraj Wagh, Dadi A Srinivasarao, Rahul Kumar, Dharmendra Kumar Khatri, Amit Asthana, Saurabh Srivastava

DOI: 10.1007/s13346-024-01669-9

摘要

乳腺癌（BC）是女性中最常见的诊断癌症。化疗、免疫疗法和光热疗法被用来治疗乳腺癌。然而，肿瘤微环境（TME）阻碍了自由药物和纳米载体（NCs）进入肿瘤区域。配方科学家依赖于增强渗透和滞留（EPR）效应来促使NCs在TME中外渗。然而，最新研究显示不同患者和肿瘤类型中EPR的表现具有不一致性。此外，血管新生、高肿瘤内液体压力、纤维化以及细胞和细胞外基质密度高等因素都阻碍了NCs在TME中的积累。在本文中，我们讨论了TME标准化作为一种改善药物和NCs渗透肿瘤区域的途径。本文还探讨了血管标准化、缺氧逆转、高肿瘤内压力缓解以及淋巴细胞渗透以逆转治疗失败的策略。还讨论了促进抗癌免疫细胞在血管标准化后渗透TME的策略。重点介绍了调控血管新生和血管正常化过程的机制途径及相关研究。本文旨在为配方科学家提供更深入的肿瘤靶向见解。

Abstract

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.