As per a report of the world health organization, an estimated 9.6 million people died due to cancer in 2018, globally. Most of the cancer death attributed to the lack of early detection and effective treatment. In the case of solid tumors, various factors such as leaky vasculature, angiogenesis, interstitial fluid pressure and lymphatic drainage are important in cancer chemotherapy. The poor penetration and retention of the drug/drug delivery system in tumor tissue are most critical issues in the way of effective treatment. In this scenario, the challenges are to design the specific nano-therapeutics with the potential to penetrate inside the adverse condition of tumor microenvironment (TME) including high interstitial pressure region and abnormal vasculature. The modification of nanocarriers surfaces with enzymes, peptides, pH-responsive moieties, antibodies etc. could be a promising strategy to improve the nanocarriers penetration inside the solid tumor. The priming with the drug before the administration of nanotherapeutics may also represents an efficient approach for solid tumor treatment. Further, the growth factors including fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF) and their pathways could offer potential targeting opportunities for anticancer treatment. Recently, there is a surge in various approaches and formulation design directed towards abnormal TME for more effective cancer therapy. In this review, various factors related to the poor penetration, retention and specific delivery of chemotherapeutics inside tumor cells/tissues are discussed. The emerging formulations strategies directed to the TME and various methodologies for evaluation of their efficacy are also included in this review.

根据世界卫生组织的报告，2018年全球估计有960万人死于癌症。大多数癌症死亡归因于缺乏早期发现和有效治疗。在实体瘤的情况下，诸如血管渗漏，血管生成，间质液压力和淋巴引流的各种因素在癌症化疗中很重要。药物/药物递送系统在肿瘤组织中的不良渗透和保留是有效治疗方式中最关键的问题。在这种情况下，面临的挑战是设计一种特定的纳米疗法，该疗法有可能渗透到肿瘤微环境（TME）的不利条件中，包括高间隙压力区域和异常脉管系统。用酶，肽，pH响应部分，抗体等可能是改善纳米载体在实体瘤内部渗透的有前途的策略。在给予纳米治疗药物之前用药物引发也可能代表一种有效的实体瘤治疗方法。此外，包括成纤维细胞生长因子（FGF），血小板衍生生长因子（PDGF），血管内皮生长因子（VEGF）及其途径在内的生长因子可以为抗癌治疗提供潜在的靶向机会。近来，针对异常TME的各种方法和制剂设计激增，以更有效地进行癌症治疗。在这篇综述中，讨论了与肿瘤细胞/组织内部化学治疗剂的不良渗透，保留和特异性递送有关的各种因素。