Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People's Republic of China.
Department of Breast Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People's Republic of China.
Int J Nanomedicine. 2024 Oct 23;19:10711-10724. doi: 10.2147/IJN.S479306. eCollection 2024.
Exosomes (Exos) are promising drug delivery systems due to their low immunogenicity, minimal toxicity, high biocompatibility, and effective delivery capabilities. However, addressing the cardiotoxicity and other toxic side effects associated with anthracyclines has proven challenging.
In this study, we loaded doxorubicin (Dox) into Exos derived from human placental mesenchymal stem cells (MSCs) and modified them with carboxylated FeO nanoparticles (NPs) to create an Exo-Dox-NP delivery system. Using an external magnetic force (MF), we regulated the distribution of Exos for targeted Dox delivery in breast cancer treatment. We characterized and determined the drug-loading efficiency of Exo-Dox-NPs, their uptake by tumor cells, and the modulation of drug release. The therapeutic efficacy of Exo-Dox-NPs was evaluated through both in vitro and in vivo anti-tumor experiments.
Our results indicated that Exo-Dox-NPs remain stable in the bloodstream while releasing the drug in the acidic environment of tumor cells and their lysosomes. As a drug delivery system, Exo-Dox-NPs enhanced Dox absorption by tumor cells, demonstrating high targeting specificity. Moreover, Exo-Dox-NPs inhibited the migration of breast cancer cells, as confirmed by scratch migration and Transwell Matrigel invasion assays. In vivo experiments confirmed the effective targeting and delivery of Dox to malignant tumors using Exo-Dox-NPs/MFs, with the Exo-Dox-NP/MF formulation exhibiting the most potent anti-tumor activity.
The utilization of Exos as carriers for Dox showed promising efficacy in breast cancer management. Carboxylated FeO NPs demonstrated to be suitable targeting agents, potentially advancing the development of natural nanocarriers for combination cancer therapy.
外泌体（Exos）由于其免疫原性低、毒性最小、生物相容性高和有效的传递能力，是很有前途的药物传递系统。然而，解决与蒽环类药物相关的心脏毒性和其他毒性副作用一直具有挑战性。
在这项研究中，我们将阿霉素（Dox）载入人胎盘间充质干细胞（MSCs）衍生的外泌体（Exos）中，并通过羧化 FeO 纳米粒子（NPs）对其进行修饰，以创建 Exo-Dox-NP 递药系统。我们利用外加磁场（MF）调节 Exos 的分布，以实现乳腺癌治疗中靶向 Dox 的递药。我们对 Exo-Dox-NP 的药物负载效率、肿瘤细胞摄取以及药物释放的调节进行了表征和测定。我们通过体外和体内抗肿瘤实验评估了 Exo-Dox-NP 的治疗效果。
我们的结果表明，Exo-Dox-NP 在血液中保持稳定，同时在肿瘤细胞的酸性环境及其溶酶体中释放药物。作为一种药物传递系统，Exo-Dox-NP 增强了肿瘤细胞对 Dox 的吸收，表现出高靶向特异性。此外，Exo-Dox-NP 抑制了乳腺癌细胞的迁移，划痕迁移和 Transwell Matrigel 侵袭实验得到了证实。体内实验证实，利用 Exo-Dox-NP/MF 有效地将 Dox 靶向递送至恶性肿瘤，其中 Exo-Dox-NP/MF 制剂表现出最强的抗肿瘤活性。
将 Exos 用作 Dox 的载体在乳腺癌管理中显示出有前景的疗效。羧化 FeO NPs 被证明是合适的靶向剂，可能会推进天然纳米载体用于联合癌症治疗的发展。
