Chemotherapy remains the primary therapeutic approach in treating cancer. The tumor microenvironment (TME) is the complex network surrounding tumor cells, comprising various cell types, such as immune cells, fibroblasts, and endothelial cells, as well as ECM components, blood vessels, and signaling molecules. The often stiff and dense network of the TME interacts dynamically with tumor cells, influencing cancer growth, immune response, metastasis, and resistance to therapy. The effectiveness of the treatment of solid tumors is frequently reduced due to the poor penetration of the drug, which leads to attaining concentrations below the therapeutic levels at the site. Cell-penetrating peptides (CPPs) present a promising approach that improves the internalization of therapeutic agents. CPPs, which are short amino acid sequences, exhibit a high ability to pass cell membranes, enabling them to deliver drugs efficiently with minimal toxicity. Specifically, the iRGD peptide, a member of CPPs, is notable for its capacity to deeply penetrate tumor tissues by binding simultaneously integrins ανβ3/ανβ5 and neuropilin receptors. Indeed, ανβ3/ανβ5 integrins are characteristically expressed by tumor cells, which allows the iRGD peptide to home onto tumor cells. Notably, the respective dual-receptor targeting mechanism considerably increases the permeability of blood vessels in tumors, enabling an efficient delivery of co-administered drugs or nanoparticles into the tumor mass. Therefore, the iRGD peptide facilitates deeper drug penetration and improves the efficacy of co-administered therapies. Distinctively, we will focus on the iRGD mechanism of action, drug delivery systems and their application, and deliberate future perspectives in developing iRGD-conjugated therapeutics. In summary, this review discusses the potential of iRGD in overcoming barriers to drug delivery in cancer to maximize treatment efficiency while minimizing side effects.
化疗仍是治疗癌症的主要方法。肿瘤微环境是围绕肿瘤细胞的复杂网络，包含多种细胞类型（如免疫细胞、成纤维细胞和内皮细胞）以及细胞外基质成分、血管和信号分子。肿瘤微环境通常具有致密坚硬的网络结构，与肿瘤细胞动态相互作用，影响癌症生长、免疫应答、转移及治疗抵抗。实体瘤的治疗效果常因药物渗透性差而降低，导致病灶部位药物浓度无法达到治疗水平。细胞穿膜肽作为一种具有前景的策略，可显著提升治疗药物的内化效率。这类短氨基酸序列具有极强的跨细胞膜能力，能够以极低毒性实现高效药物递送。其中，iRGD肽作为细胞穿膜肽家族成员，因其能同时结合整合素ανβ3/ανβ5与神经纤毛蛋白受体而表现出卓越的肿瘤组织深层渗透能力。值得注意的是，ανβ3/ανβ5整合素在肿瘤细胞中特异性表达，使iRGD肽能够靶向富集于肿瘤细胞。其独特的双受体靶向机制可显著增强肿瘤血管通透性，实现共给药或纳米颗粒的高效肿瘤富集。因此，iRGD肽能促进药物深层渗透并提升联合疗法的疗效。本文将重点探讨iRGD的作用机制、药物递送系统及其应用，并对iRGD偶联疗法的未来发展前景进行展望。本综述系统阐述了iRGD在突破肿瘤药物递送屏障方面的潜力，以期在最大化治疗效果的同时最小化副作用。
Enhancing Tumor Targeted Therapy: The Role of iRGD Peptide in Advanced Drug Delivery Systems
肿瘤(癌症)患者之家