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Study on glycol chitosan based nanoparticles for tumor specific CT/US dual imaging

초록/요약

Targeted imaging systems that can access early and detailed information on diseases have received much attention as an alternative to conventional contrast agents. The development of polymeric nanoparticles for cancer-targeted imaging in clinics still remains challenging due to few resolution and sensitivity. Multimodal imaging has recently come into the spotlight in order to these limitations. We suggest here that iodinated and echogenic nanoparticles are useful as computed tomography (CT) and ultrasound (US) imaging concurrently for early-detection and real-time monitoring for cancer. In this study, CT/US dual imaging system was prepared by following bellow two step: First, the diatrizoic acid (DTA) as a CT contrast agent was conjugated to the backbone of the glycol chitosan (GC). And, perfluoropentane (PFP), a US contrast agent, was encapsulated into the GC-DTAs by O/W emulsion method, leading to GC-DTA-PFP nanoparticles with CT/US contrast agents. The GC-DTA-PFP NPs appeared a stable spherical nanostructure in physiological environment, and it was monitored to in vitro CT and US signal, respectively. The nanoparticles were effectively accumulated into the tumor site by EPR-effects, allowing to tumor-specific CT/US imaging. This approach to developing iodinated and echogenic nanoparticles may provide useful strategy for early detection of tumor region by fast whole-body CT scanning and then those real-time monitoring by US imaging.

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초록/요약

본 연구에서는 기존의 computed tomography (CT) 조영제와 ultrasound (US) 조영제의 한계점을 극복하고 각각 영상의 장점을 융합한 암 표적형 CT/US 이중 영상화를 진행하였다. 생체 적합성 고분자인 glycol chitosan (GC)에 소수성 분자인 diatrizoic acid (DTA)를 접합하여 CT 영상이 가능한 나노입자를 합성하였다. 제조된 나노입자에 초음파 영상 적용을 위해 perfluoropentane (PFP)를 봉입하여 CT/US 이중 영상화가 가능한 조영제를 개발하였다. 제조된 나노입자의 물리화학적인 특성을 DLS, TEM, UV-vis 등을 통하여 평가하였고, MTT assay를 통해 나노입자의 세포 내 독성을 평가하였다. 또한 나노입자의 이중 영상화에 대한 가능성을 in vitro 상에서 CT와 US를 통해서 확인하였다. glycolchitosan 기반의 나노입자는 종양 부위에 선택적으로 축적 되는 거동을 확인하였고, 종양 동물 모델에서 CT와 US의 이중 영상화를 확인하였다. 본 연구를 통해 개발된 나노입자는 CT를 통해 종양의 위치 정보를 획득하고, US를 통해 질병 부위의 구체적인 실시간 정보를 획득 할 수 있다.

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