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α-Lipoic acid stabilized DTX/IR780 micelles for photoacoustic/fluorescence imaging guided photothermal therapy/chemotherapy of breast cancer
Biomaterials Science ( IF 5.8 ) Pub Date : 2018-03-12 00:00:00 , DOI: 10.1039/c8bm00096d
WenTing Li 1, 2, 3, 4, 5 , JinRong Peng 1, 2, 3, 4, 5 , Qian Yang 4, 5, 6, 7 , LiJuan Chen 1, 2, 3, 4, 5 , Lan Zhang 5, 8, 9, 10, 11 , XiaoXin Chen 5, 8, 9, 10, 11 , ZhiYong Qian 1, 2, 3, 4, 5
Affiliation  

Micellar nanoparticles have unique advantages as carriers for therapeutic or imaging agents, owing to their smaller size and better penetration of tumors. However, some agents, due to their physical or chemical properties, are difficult to load into micelles. IR780 is one of these agents, and is also a promising near-infrared dye for fluorescence imaging (FI)/photoacoustic imaging (PAI) and cancer photothermal therapy (PTT). Its hydrophobic and high crystallization structure results in limited bioavailability in vivo. It is difficult to load into micelles constructed from an amphiphilic block polymer with relatively low molecular weight. In this study, we use computer simulation and introduce another small biomolecule, α-lipoic acid, into the micelles constructed from a mPEG-PCL copolymer, to lower the energy of molecular interaction between MPEG-PCL and IR780, and expect to enhance the loading capacity of the micelles to IR780. The introduction of α-lipoic acid decreases the energy of molecular interaction between MEPG-PCL and IR780 from −46.18 kJ mol−1 to −196.52 kJ mol−1 and increases the loading capacity and stability of the mPEG-PCL micelles to IR780, which also maintains the loading capacity to DTX. We further construct DTX/IR780 co-loaded mPEG-PCL micelles for FI/PAI dual modal imaging guided PTT/chemotherapy of cancer. By FI and PAI evaluation in vitro and in vivo, we demonstrate that the DTX/IR780 co-loaded micelles can be used as FI and PAI probes. By further evaluating the therapeutic outcome of PTT/chemotherapy co-therapy of breast cancer, we demonstrate that the DTX/IR780 co-loaded mPEG-PCL micelles can serve as promising candidates for FI and PAI guided PTT/chemotherapy of breast cancer.

中文翻译:

α-硫辛酸稳定的DTX / IR780胶束,用于光声/荧光成像引导的乳腺癌光热疗法/化学疗法

胶束纳米颗粒由于其较小的尺寸和更好的肿瘤渗透性而具有作为治疗剂或显像剂载体的独特优势。但是,某些试剂由于其物理或化学性质,很难加载到胶束中。IR780是这些试剂之一,也是用于荧光成像(FI)/光声成像(PAI)和癌症光热疗法(PTT)的有前途的近红外染料。其疏水性和高结晶结构导致体内生物利用度有限。难以加载到由具有相对低分子量的两亲性嵌段聚合物构成的胶束中。在这项研究中,我们使用计算机模拟,并将另一种小的生物分子α-硫辛酸引入由mPEG-PCL共聚物构成的胶束中,以降低MPEG-PCL和IR780之间的分子相互作用能,并期望增加负载胶束达到IR780的能力。α-硫辛酸的引入将MEPG-PCL和IR780之间的分子相互作用能从-46.18 kJ mol -1降低到-196.52 kJ mol -1并提高了mPEG-PCL胶束对IR780的负载能力和稳定性,这也保持了对DTX的负载能力。我们进一步构建DTX / IR780共装载的mPEG-PCL胶束,用于FI / PAI双模态成像指导的PTT /癌症化疗。通过FI和PAI在体外体内的评估,我们证明DTX / IR780共同加载的胶束可用作FI和PAI探针。通过进一步评估PTT /化学疗法联合治疗乳腺癌的治疗结果,我们证明DTX / IR780共同加载的mPEG-PCL胶束可以作为FI和PAI指导的PTT /化学疗法治疗乳腺癌的有希望的候选者。
更新日期:2018-03-12
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