Alfawaz Altamimi Abdulmalik Saleh, Arockia Babu M, Afzal Muhammad, Bishoyi Ashok Kumar, Roopashree R, Saini Suman, Sharma R S K, Pathak Piyus Kumar, Chauhan Ashish Singh, Goyal Kavita, Ali Haider, Khan Nawaid Hussain, Balaraman Ashok Kumar
Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, 11942, Al Kharj, Saudi Arabia.
Institute of Pharmaceutical Research, GLA University, Mathura, Uttar Pradesh, India.
Med Oncol. 2025 Mar 18;42(4):114. doi: 10.1007/s12032-025-02647-y.
Natural killer cell-derived exosomes (NK-Exos) hold great promise as immune modulators and immunotherapeutics against cancer due to their intrinsically latent anti-tumor effects. They use these nanosized vesicles to deliver cytotoxic molecules, such as perforin, granzymes, and miRNAs, directly to cancer cells to kill them, avoiding immune suppression. NK-Exos has particular efficacy for treating aggressive breast cancer by modulating the TME to activate the immune response and suppress immunosuppressive factors. Bioengineering advances have extended the therapeutic potential of NK-Exos, which permits precise tumor cell targeting and efficient delivery of therapeutic payloads, including small RNAs and chemotherapeutic agents. In engineered NK-Exos, sensitization of cancer cells to apoptosis, reduction of tumor growth, and resistance to drugs have been demonstrated to be highly effective. When combined, NK-Exos synergizes with radiotherapy, chemotherapy, or checkpoint inhibitors, enhancing therapeutic efficacy, and minimizing systemic toxicity. This review emphasizes the critical role of NK-Exos in breast cancer treatment, their integration into combination therapies, and the need for further research to overcome existing limitations and fully realize their clinical potential.
自然杀伤细胞衍生的外泌体（NK-Exos）由于其内在的潜在抗肿瘤作用，作为免疫调节剂和抗癌免疫疗法具有巨大的潜力。它们利用这些纳米大小的囊泡将细胞毒性分子，如穿孔素、颗粒酶和微小RNA，直接递送至癌细胞以杀死它们，从而避免免疫抑制。NK-Exos通过调节肿瘤微环境以激活免疫反应并抑制免疫抑制因子，在治疗侵袭性乳腺癌方面具有特殊疗效。生物工程的进展扩展了NK-Exos的治疗潜力，使其能够精确靶向肿瘤细胞并有效递送治疗有效载荷，包括小RNA和化疗药物。在工程化的NK-Exos中，已证明癌细胞对凋亡的敏感性增加、肿瘤生长减少以及对药物的抗性均非常有效。当联合使用时，NK-Exos与放疗、化疗或检查点抑制剂协同作用，提高治疗效果，并将全身毒性降至最低。本综述强调了NK-Exos在乳腺癌治疗中的关键作用、它们在联合疗法中的整合，以及进一步研究以克服现有局限性并充分实现其临床潜力的必要性。
