Aldhubiab Bandar, Almuqbil Rashed M, Nair Anroop B
Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia.
Pharmaceuticals (Basel). 2025 May 19;18(5):746. doi: 10.3390/ph18050746.
The tumor microenvironment (TME) has a major role in malignancy and its complex nature can mediate tumor survival, metastasis, immune evasion, and drug resistance. Thus, reprogramming or regulating the immunosuppressive TME has a significant contribution to make in cancer therapy. Targeting TME with nanocarriers (NCs) has been widely used to directly deliver anticancer drugs to control TME, which has revealed auspicious outcomes. TME can be reprogrammed by using a range of NCs to regulate immunosuppressive factors and activate immunostimulatory cells. Moreover, TME can be ameliorated via regulating the redox environment, oxygen content, and pH value of the tumor site. NCs have the capacity to provide site-specific delivery of therapeutic agents, controlled release, enhanced solubility and stability, decreased toxicities, and enhanced pharmacokinetics as well as biodistribution. Numerous NCs have demonstrated their potential by inducing distinct anticancer mechanisms by delivering a range of anticancer drugs in various preclinical studies, including metal NCs, liposomal NCs, solid lipid NCs, micelles, nanoemulsions, polymer-based NCs, dendrimers, nanoclays, nanocrystals, and many more. Some of them have already received US Food and Drug Administration approval, and some have entered different clinical phases. However, there are several challenges in NC-mediated TME targeting, including scale-up of NC-based cancer therapy, rapid clearance of NCs by the mononuclear phagocyte system, and TME heterogeneity. In order to harness the full potential of NCs in tumor treatment, there are several factors that need to be carefully studied, including optimization of drug loading into NCs, NC-associated immunogenicity, and biocompatibility for the successful translation of NC-based anticancer therapies into clinical practice. In this review, a range of NCs and their applications in drug delivery to remodel TME for cancer therapy are extensively discussed. Moreover, findings from numerous preclinical and clinical studies with these NCs are also highlighted.
肿瘤微环境（TME）在恶性肿瘤中起着重要作用，其复杂的性质可介导肿瘤存活、转移、免疫逃逸和耐药性。因此，重新编程或调节免疫抑制性肿瘤微环境对癌症治疗具有重大贡献。用纳米载体（NCs）靶向肿瘤微环境已被广泛用于直接递送抗癌药物以控制肿瘤微环境，这已显示出良好的效果。通过使用一系列纳米载体来调节免疫抑制因子并激活免疫刺激细胞，可以对肿瘤微环境进行重新编程。此外，通过调节肿瘤部位的氧化还原环境、氧含量和pH值，可以改善肿瘤微环境。纳米载体有能力实现治疗剂的位点特异性递送、控释、提高溶解度和稳定性、降低毒性以及改善药代动力学和生物分布。在各种临床前研究中，许多纳米载体通过递送一系列抗癌药物诱导不同的抗癌机制，从而展现出了它们的潜力，包括金属纳米载体、脂质体纳米载体、固体脂质纳米载体、胶束、纳米乳剂、聚合物基纳米载体、树枝状大分子、纳米粘土、纳米晶体等等。其中一些已经获得美国食品药品监督管理局的批准，还有一些已经进入不同的临床阶段。然而，纳米载体介导的肿瘤微环境靶向存在几个挑战，包括基于纳米载体的癌症治疗的扩大规模、单核吞噬细胞系统对纳米载体的快速清除以及肿瘤微环境的异质性。为了充分发挥纳米载体在肿瘤治疗中的潜力，需要仔细研究几个因素，包括优化纳米载体中的药物负载、纳米载体相关的免疫原性以及生物相容性，以便将基于纳米载体的抗癌疗法成功转化为临床实践。在这篇综述中，广泛讨论了一系列纳米载体及其在药物递送中重塑肿瘤微环境用于癌症治疗的应用。此外，还强调了使用这些纳米载体的众多临床前和临床研究的结果。
