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Responsive Nanomicellar Theranostic Cages for Metastatic Breast Cancer
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2018-01-11 00:00:00 , DOI: 10.1021/acs.bioconjchem.7b00577 Amrutha Manigandan 1 , Vandhana Handi 1 , Niranjana Sri Sundaramoorthy 1 , Ramya Dhandapani 1 , Janani Radhakrishnan 1 , Swaminathan Sethuraman 1 , Anuradha Subramanian 1
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2018-01-11 00:00:00 , DOI: 10.1021/acs.bioconjchem.7b00577 Amrutha Manigandan 1 , Vandhana Handi 1 , Niranjana Sri Sundaramoorthy 1 , Ramya Dhandapani 1 , Janani Radhakrishnan 1 , Swaminathan Sethuraman 1 , Anuradha Subramanian 1
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Precluding the progression of metastasis with early diagnosis of triple-negative breast cancer remains challenging due to lack of targeting specificity with poor diagnostic potential. Herein, an amphipathic chitosan-based targeted nanomicellar theranostics (30–45 nm) comprising doxorubicin–superparamagnetic iron oxide nanoparticles complexes (89.23%) with lower critical micelle concentration (0.1 μg/mL) were developed. Micelles exhibit concentration-based contrast enhancement in MRI (r2 6.27 mM–1 s–1) and hyperthermia rather than thermal-ablation. This theranostics delivers doxorubicin under alternating magnetic field (480 kHz) and at endosomal pH (pH 5.2) while showing stability at pH 7.4. Anti-αvβ3 integrin antibody conjugation onto PEGylated micelles (62.3%) enhances micellar internalization into drug-resistant MDA-MB-231 after 1 h and magnetizes the cells after 6 h over that with nonconjugated micelles. Immigration of MDA-MB-231 and 4T1 cells retards after 24 h, while significant reduction of mitochondrial membrane potential is observed under hyperthermia. Intratumoral administration of nanomicelles in 4T1 orthotopic spontaneous metastasis model demonstrated antitumor and fibrosis mediated caging effect with simultaneous enhancement of MRI-T2 contrast.
中文翻译：
响应性Nanomicellar治疗性笼子转移性乳腺癌。
由于缺乏靶向特异性且诊断潜能低，在早期诊断三阴性乳腺癌中排除转移的进展仍然具有挑战性。在本文中，开发了一种基于两亲壳聚糖的靶向纳米胶束治疗剂（30-45 nm），该胶束包含具有较低临界胶束浓度（0.1μg/ mL）的阿霉素-超顺磁性氧化铁纳米颗粒复合物（89.23％）。胶束在MRI（r2 6.27 mM –1 s –1）和热疗中表现出基于浓度的对比增强，而不是热消融。该治疗学疗法在交变磁场（480 kHz）和内体pH（pH 5.2）下递送阿霉素，而在pH 7.4时显示出稳定性。抗α v β 3与未缀合的胶束相比，整合素抗体与PEG化胶束（62.3％）的缀合可增强胶束内化至耐药MDA-MB-231的能力，并在6 h后使细胞磁化。MDA-MB-231和4T1细胞的迁移在24小时后延迟，而在高温下观察到线粒体膜电位显着降低。在4T1原位自发转移模型中瘤内施用纳米胶束证明了抗肿瘤和纤维化介导的笼养效应，同时增强了MRI-T 2对比。
更新日期：2018-01-11
中文翻译：
响应性Nanomicellar治疗性笼子转移性乳腺癌。
由于缺乏靶向特异性且诊断潜能低，在早期诊断三阴性乳腺癌中排除转移的进展仍然具有挑战性。在本文中，开发了一种基于两亲壳聚糖的靶向纳米胶束治疗剂（30-45 nm），该胶束包含具有较低临界胶束浓度（0.1μg/ mL）的阿霉素-超顺磁性氧化铁纳米颗粒复合物（89.23％）。胶束在MRI（r2 6.27 mM –1 s –1）和热疗中表现出基于浓度的对比增强，而不是热消融。该治疗学疗法在交变磁场（480 kHz）和内体pH（pH 5.2）下递送阿霉素，而在pH 7.4时显示出稳定性。抗α v β 3与未缀合的胶束相比，整合素抗体与PEG化胶束（62.3％）的缀合可增强胶束内化至耐药MDA-MB-231的能力，并在6 h后使细胞磁化。MDA-MB-231和4T1细胞的迁移在24小时后延迟，而在高温下观察到线粒体膜电位显着降低。在4T1原位自发转移模型中瘤内施用纳米胶束证明了抗肿瘤和纤维化介导的笼养效应，同时增强了MRI-T 2对比。
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