Chen Kuo-Wei, Hsu Po-Hung, Huang Hau-Lun, Liu Hao-Li, Lin Ya-Tin, Hsu Che-Yu, Lin Jui-Hsiang, Lin Yu-Hsin
Division of Hematology and Oncology, Cheng Hsin General Hospital, Taipei, Taiwan.
Department of Medical Research and Development, Chang Gung Memorial Hospital, Linkou, Taiwan.
Pharmacol Res. 2022 Dec;186:106532. doi: 10.1016/j.phrs.2022.106532. Epub 2022 Nov 2.
The stress of the abnormal stromal matrix of solid tumors is a major limiting factor that prevents drug penetration. Controlled, accurate, and efficient delivery of theranostic agents into tumor cells is crucial. Combining ultrasound with nanocarrierbased drug delivery systems have become a promising approach for targeted drug delivery in preclinical cancer therapy. In this study, to ensure effective tumor barrier penetration, access to the tumor microenvironment, and local drug release, we designed targeted nanoparticle (NP)-conjugated microbubbles (MBs); ultrasound could then help deliver acoustic energy to release the NPs from the MBs. The ultrasound-targeted MB destruction (UTMD) system of negatively charged NPs was conjugated with positively charged MBs using an ionic gelation method. We demonstrated the transfer of targeted NPs and their entry into gastric cancer cells through ligand-specific recognition, followed by enhanced cell growth inhibition owing to drug delivery-induced apoptosis. Moreover, the UTMD system combining therapeutic and ultrasound image properties can effectively target gastric cancer, thus significantly enhancing antitumor activity, as evident by tumor localization in an orthotopic mouse model of gastric cancer. The combination of ultrasound and NP-based drug delivery systems has become a promising approach for targeted drug delivery in preclinical cancer therapy.
实体瘤异常基质的应力是阻碍药物渗透的主要限制因素。将治疗诊断剂可控、准确且高效地递送至肿瘤细胞至关重要。将超声与基于纳米载体的药物递送系统相结合已成为临床前癌症治疗中靶向药物递送的一种有前景的方法。在本研究中，为确保有效穿透肿瘤屏障、进入肿瘤微环境并实现局部药物释放，我们设计了靶向纳米颗粒（NP）偶联的微泡（MB）；然后超声可帮助传递声能以从MB中释放NP。使用离子凝胶法将带负电荷的NP的超声靶向MB破坏（UTMD）系统与带正电荷的MB偶联。我们证明了靶向NP的转移及其通过配体特异性识别进入胃癌细胞，随后由于药物递送诱导的凋亡而增强了细胞生长抑制。此外，结合治疗和超声成像特性的UTMD系统可有效靶向胃癌，从而显著增强抗肿瘤活性，这在胃癌原位小鼠模型中的肿瘤定位中得到了证实。超声与基于NP的药物递送系统的结合已成为临床前癌症治疗中靶向药物递送的一种有前景的方法。
