Department of Chemical and Biomolecular Engineering, University of Notre Dame, 205C McCourtney Hall, Notre Dame, IN, 46556-5637, USA.
Harper Center Research Institute, University of Notre Dame, Notre Dame, IN, 46556, USA.
J Hematol Oncol. 2020 Nov 2;13(1):145. doi: 10.1186/s13045-020-00965-4.
Drug-loaded nanoparticles have established their benefits in the fight against multiple myeloma; however, ligand-targeted nanomedicine has yet to successfully translate to the clinic due to insufficient efficacies reported in preclinical studies.
In this study, liposomal nanoparticles targeting multiple myeloma via CD38 or CD138 receptors are prepared from pre-synthesized, purified constituents to ensure increased consistency over standard synthetic methods. These nanoparticles are then tested both in vitro for uptake to cancer cells and in vivo for accumulation at the tumor site and uptake to tumor cells. Finally, drug-loaded nanoparticles are tested for long-term efficacy in a month-long in vivo study by tracking tumor size and mouse health.
The targeted nanoparticles are first optimized in vitro and show increased uptake and cytotoxicity over nontargeted nanoparticles, with CD138-targeting showing superior enhancement over CD38-targeted nanoparticles. However, biodistribution and tumor suppression studies established CD38-targeted nanoparticles to have significantly increased in vivo tumor accumulation, tumor cell uptake, and tumor suppression over both nontargeted and CD138-targeted nanoparticles due to the latter's poor selectivity.
These results both highlight a promising cancer treatment option in CD38-targeted nanoparticles and emphasize that targeting success in vitro does not necessarily translate to success in vivo.
载药纳米颗粒在对抗多发性骨髓瘤方面已经显示出其优势；然而，由于临床前研究中报道的疗效不足，配体靶向纳米医学尚未成功转化为临床应用。
在这项研究中，通过 CD38 或 CD138 受体靶向多发性骨髓瘤的脂质体纳米颗粒是由预先合成、纯化的成分制备而成，以确保比标准合成方法更高的一致性。然后，在体外测试这些纳米颗粒对癌细胞的摄取能力，以及在体内测试其在肿瘤部位的积累和对肿瘤细胞的摄取能力。最后，通过跟踪肿瘤大小和小鼠健康状况，在为期一个月的体内研究中测试载药纳米颗粒的长期疗效。
靶向纳米颗粒首先在体外进行优化，显示出比非靶向纳米颗粒更高的摄取率和细胞毒性，CD138 靶向显示出比 CD38 靶向纳米颗粒更高的增强效果。然而，生物分布和肿瘤抑制研究表明，由于后者的选择性差，CD38 靶向纳米颗粒在体内肿瘤积累、肿瘤细胞摄取和肿瘤抑制方面明显优于非靶向和 CD138 靶向纳米颗粒。
这些结果既突出了 CD38 靶向纳米颗粒作为一种有前途的癌症治疗选择，也强调了体外靶向成功并不一定能转化为体内成功。
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