Stukan Iga, Żuk Anna, Pukacka Kamila, Mierzejewska Julia, Pawłowski Jakub, Kowalski Bogusław, Dąbkowska Maria
Department of General Pathology, Pomeranian Medical University in Szczecin, Szczecin, Poland.
Independent Laboratory of Community Pharmacy, Pomeranian Medical University in Szczecin, Szczecin, Poland.
Int J Nanomedicine. 2025 Mar 19;20:3493-3525. doi: 10.2147/IJN.S500997. eCollection 2025.
Human serum albumin (HSA) has emerged as a promising carrier for nanodrug delivery, offering unique structural properties that can be engineered to overcome key challenges in cancer treatment, especially resistance to chemotherapy. This review focuses on the cellular uptake of albumin-based nanoparticles and the modifications that enhance their ability to bypass resistance mechanisms, particularly multidrug resistance type 1 (MDR1), by improving targeting to cancer cells. In our unique approach, we integrate the chemical properties of albumin, its interactions with cancer cells, and surface modifications of albumin-based delivery systems that enable to bypass resistance mechanisms, particularly those related to MDR1, and precisely target receptors on cancer cells to improve treatment efficacy. We discuss that while well-established albumin receptors such as gp60 and gp18/30 are crucial for cellular uptake and transcytosis, their biology remains underexplored, limiting their translational potential. Additionally, we explore the potential of emerging targets, such as cluster of differentiation 44 (CD44), cluster of differentiation (CD36) and transferrin receptor TfR1, as well as the advantages of using dimeric forms of albumin (dHSA) to further enhance delivery to resistant cancer cells. Drawing from clinical examples, including the success of albumin-bound paclitaxel (Abraxane) and new formulations like Pazenir and Fyarro (for Sirolimus), we identify gaps in current knowledge and propose strategies to optimize albumin-based systems. In conclusion, albumin-based nanoparticles, when tailored with appropriate modifications, have the potential to bypass multidrug resistance and improve the targeting of cancer cells. By enhancing albumin's ability to efficiently deliver therapeutic agents, these carriers represent a promising approach to addressing one of oncology's most persistent challenges, with substantial potential to improve cancer treatment outcomes.
人血清白蛋白（HSA）已成为纳米药物递送中一种很有前景的载体，它具有独特的结构特性，可通过工程设计来克服癌症治疗中的关键挑战，尤其是对化疗的耐药性。本综述聚焦于基于白蛋白的纳米颗粒的细胞摄取以及能增强其绕过耐药机制（特别是多药耐药1型，即MDR1）能力的修饰，方法是改善对癌细胞的靶向性。在我们独特的方法中，我们整合了白蛋白的化学性质、其与癌细胞的相互作用以及基于白蛋白的递送系统的表面修饰，这些修饰能够绕过耐药机制，特别是与MDR1相关的机制，并精确靶向癌细胞上的受体以提高治疗效果。我们讨论到，虽然诸如gp60和gp18/30等已确立的白蛋白受体对细胞摄取和转胞吞作用至关重要，但其生物学特性仍未得到充分探索，限制了它们的转化潜力。此外，我们还探讨了新兴靶点（如分化簇44，即CD44、分化簇CD36和转铁蛋白受体TfR1）的潜力，以及使用白蛋白二聚体形式（dHSA）进一步增强对耐药癌细胞递送的优势。从临床实例（包括白蛋白结合型紫杉醇，即Abraxane的成功以及Pazenir和Fyarro（用于西罗莫司）等新制剂）出发，我们确定了当前知识中的空白，并提出了优化基于白蛋白系统的策略。总之，基于白蛋白的纳米颗粒经过适当修饰后，有潜力绕过多药耐药并改善对癌细胞的靶向性。通过增强白蛋白有效递送治疗药物的能力，这些载体代表了一种有前景的方法来应对肿瘤学中最持久的挑战之一，具有显著改善癌症治疗结果的潜力。
