Min Hyun Su, You Dong Gil, Son Sejin, Jeon Sangmin, Park Jae Hyung, Lee Seulki, Kwon Ick Chan, Kim Kwangmeyung
1. Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 6, Seongbuk-gu, Seoul 136-791, South Korea.
1. Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 6, Seongbuk-gu, Seoul 136-791, South Korea ; 2. School of chemical engineering, Sungkyunkwan University, Suwon 440-746, South Korea.
Theranostics. 2015 Oct 18;5(12):1402-18. doi: 10.7150/thno.13099. eCollection 2015.
Theranostic nanoparticles hold great promise for simultaneous diagnosis of diseases, targeted drug delivery with minimal toxicity, and monitoring of therapeutic efficacy. However, one of the current challenges in developing theranostic nanoparticles is enhancing the tumor-specific targeting of both imaging probes and anticancer agents. Herein, we report the development of tumor-homing echogenic glycol chitosan-based nanoparticles (Echo-CNPs) that concurrently execute cancer-targeted ultrasound (US) imaging and US-triggered drug delivery. To construct this novel Echo-CNPs, an anticancer drug and bioinert perfluoropentane (PFP), a US gas precursor, were simultaneously encapsulated into glycol chitosan nanoparticles using the oil in water (O/W) emulsion method. The resulting Echo-CNPs had a nano-sized particle structure, composing of hydrophobic anticancer drug/PFP inner cores and a hydrophilic glycol chitosan polymer outer shell. The Echo-CNPs had a favorable hydrodynamic size of 432 nm, which is entirely different from the micro-sized core-empty conventional microbubbles (1-10 μm). Furthermore, Echo-CNPs showed the prolonged echogenicity via the sustained microbubble formation process of liquid-phase PFP at the body temperature and they also presented a US-triggered drug release profile through the external US irradiation. Interestingly, Echo-CNPs exhibited significantly increased tumor-homing ability with lower non-specific uptake by other tissues in tumor-bearing mice through the nanoparticle's enhanced permeation and retention (EPR) effect. Conclusively, theranostic Echo-CNPs are highly useful for simultaneous cancer-targeting US imaging and US-triggered delivery in cancer theranostics.
诊疗纳米粒子在疾病的同步诊断、低毒性靶向药物递送以及治疗效果监测方面具有巨大潜力。然而，目前开发诊疗纳米粒子面临的挑战之一是提高成像探针和抗癌药物对肿瘤的特异性靶向性。在此，我们报告了一种肿瘤归巢的基于乙二醇壳聚糖的超声造影纳米粒子（Echo-CNPs）的开发，该纳米粒子可同时实现癌症靶向超声（US）成像和超声触发的药物递送。为构建这种新型的Echo-CNPs，使用水包油（O/W）乳液法将一种抗癌药物和生物惰性的全氟戊烷（PFP，一种超声造影剂前体）同时封装到乙二醇壳聚糖纳米粒子中。所得的Echo-CNPs具有纳米级的粒子结构，由疏水性抗癌药物/PFP内核和亲水性乙二醇壳聚糖聚合物外壳组成。Echo-CNPs具有良好的流体动力学尺寸，为432nm，这与微米级的空心传统微泡（1-10μm）完全不同。此外，Echo-CNPs通过在体温下液相PFP的持续微泡形成过程表现出延长的回声性，并且它们还通过外部超声照射呈现出超声触发的药物释放曲线。有趣的是，通过纳米粒子的增强渗透和滞留（EPR）效应，Echo-CNPs在荷瘤小鼠中表现出显著增强的肿瘤归巢能力，且其他组织的非特异性摄取较低。总之，诊疗用Echo-CNPs在癌症诊疗中对于同时进行癌症靶向超声成像和超声触发递送非常有用。
