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Tumor intracellular microenvironment-responsive nanoparticles for magnetically targeted chemotherapy
Kangmin Noh,Saji Uthaman,이충성,Yugyeong Kim,Shameer Pillarisetti,Hee Sook Hwang,In-Kyu Park,Kang Moo Huh 한국공업화학회 2022 Journal of Industrial and Engineering Chemistry Vol.111 No.-
Nanoparticles (NPs) with responsive modalities in biological microenvironments and external stimulihave received great attention as highly efficient and precise cancer therapy agents. In this study, tumorintracellular microenvironment-responsive NPs co-assembled from poly(ethylene glycol)-poly(asparticacid) [PEG-P(Asp)] copolymer, doxorubicin (DOX), and superparamagnetic iron oxide NPs (SPIONs), termedas PEG-P(Asp)/DOX/SPIONs, were prepared for tumor intracellular microenvironment (enzyme andpH)-responsive and magnetically targeted chemotherapy. The NPs exhibited not only enzyme-responsivedegradation in the presence of protease, but also triggered release of DOX at pH 5, which is an aciditysimilar to endolysosomal microenvironments in tumor cells. Furthermore, the PEG-P(Asp)/DOX/SPIONsshowed a contrast effect in magnetic resonance imaging. In vitro viability assays showed that PEG-P(Asp)/DOX/SPIONs could effectively augment the cytocompatibility of DOX compared to free DOX withouta change in magnetic forces. Fluorescence microscopy images indicated that the fabricated NPs efficientlyincreased the targeted uptake and release of DOX within cells. Overall, this hybrid NP systemcould be a favorable biomedical agent for effective tumor-targeted anti-cancer therapy.
암 치료를 위한 Poly(ethylene glycol)-Doxorubicin/SPION 자성 나노입자의 제조 및 특성분석
김유경(Yugyeong Kim),이선민(Seonmin Lee),김단비(Danbee Kim),노강민(Kangmin Noh),오근상(Keun Sang Oh),조성훈(Sunghoon Cho),최은표(Eunpyo Choi),김규표(Kyu-pyo Kim),허강무(Kang Moo Huh) 한국고분자학회 2018 폴리머 Vol.42 No.6
본 연구에서는 친수성 poly(ethylene glycol)(PEG)와 소수성 항암제인 독소루비신(DOX)의 화학적 결합에 의해 합성된 PEG-DOX conjugate를 이용하여 암 진단 및 치료가 가능한 자성 나노입자를 제조하고자 하였다. 양친매성 PEG-DOX는 수용액 내에서 자기조립 특성을 보이고, 10 ㎚ 내외의 자성 나노입자(SPION)에 대해 높은 봉입능 및 봉입률을 보였다. 제조된 PEG-DOX/SPION 나노입자는 ~100 ㎚의 균일한 사이즈 분포를 가지며 phantom 실험을 통해 조영제로서의 가능성을 확인하였다. 세포독성평가에서 DOX에 비해 낮은 독성을 보였고 최대내성용량(MTD) 평가실험에서 사망 개체가 발생하지 않았다. 결과적으로, 고함량의 항암제와 SPION으로 구성된 본 나노입자 시스템은 낮은 독성, MR 조영 특성, 수동적 및 자성 표적화능 등 다양한 생기능성을 기반으로 암 진단 및 치료에 유용한 테라그노스틱 제형에 응용될 수 있을 것으로 기대한다. In this study, an amphiphilic polymer-drug conjugate was synthesized by chemical conjugation of a hydrophilic polymer poly(ethylene glycol) (PEG) with a hydrophobic anticancer agent, doxorubicin (DOX), to prepare magnetic nanoparticles for cancer diagnosis and therapy. The amphiphilic PEG-DOX polymer could self-assemble in the aqueous solution to form nanoparticles (NPs) and efficiently encapsulated superparamagnetic iron oxide nanoparticles (SPION) with high loading capacity and loading efficiency. The resulting SPION encapsulated PEG-DOX (PEG-DOX/SPION) NPs were observed to have an average size of ~100 ㎚ with a narrow and unimodal size distribution and demonstrated the characteristic of MR contrast agent from the phantom experiments. In the toxicity assessment, PEG-DOX/SPION NPs showed lower toxicity than pristine DOX, and no mortality was detected at the maximum MTD. As a result, these magnetic NPs with high contents of DOX and SPION could be utilized as a theragnostic formulation for efficient cancer diagnosis and therapy, due to their diverse potential capacities properties, such as low toxicity, MR imaging character, passive and magnetic targeting properties, and so on.