Shortwave Infrared-Emitting Theranostics for Breast Cancer Therapy Response Monitoring.
Shortwave Infrared-Emitting Theranostics for Breast Cancer Therapy Response Monitoring.
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DOI：
10.3389/fmolb.2020.569415
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发表时间：
2020
影响因子：
5
通讯作者：
Ganapathy V
中科院分区：
文献类型：
--
作者：
Shah JV;Gonda A;Pemmaraju R;Subash A;Bobadilla Mendez C;Berger M;Zhao X;He S;Riman RE;Tan MC;Pierce MC;Moghe PV;Ganapathy V
癌症治疗药物监测（TDM）虽然势在必行，但由于药物药代动力学的患者间差异，一直具有挑战性。此外，大多数药代动力学监测是通过评估血浆中的药物来完成的，这并不能准确衡量目标肿瘤组织中的药物浓度。目前迫切需要一种治疗监测工具，能够提供靶点药物疗效的实时反馈，以便在癌症治疗早期改变治疗方案。在这里，我们报道了基于短波红外（SWIR）发射稀土掺杂纳米颗粒包裹人血清白蛋白（简称ReANCs）的治疗性光学成像探针，该探针在检测乳腺癌转移小鼠模型中1厘米深度的微病变方面表现出卓越的监测能力。最值得注意的是，以前用于检测多器官转移的ReANCs比对比增强磁共振成像（MRI）更早地解决了骨病变。我们设计了肿瘤靶向ReANCs，携带治疗有效载荷，作为评估肿瘤部位药物疗效的潜在治疗手段。体外结果表明，携带阿霉素（Dox）的ReANCs有效，在保持与游离阿霉素相当的细胞毒性作用的同时，提供阿霉素的持续释放。值得注意的是，在小鼠乳腺癌肺转移模型中，我们证明了基于肿瘤靶向ReANCs的SWIR荧光测量的治疗监测能力。这些发现与肺转移负担的减少相关，通过基于mri的体积分析在四周的过程中量化。未来的研究将探讨这种新型治疗方法作为临床前药理学筛选工具的潜力。
Therapeutic drug monitoring (TDM) in cancer, while imperative, has been challenging due to inter-patient variability in drug pharmacokinetics. Additionally, most pharmacokinetic monitoring is done by assessments of the drugs in plasma, which is not an accurate gauge for drug concentrations in target tumor tissue. There exists a critical need for therapy monitoring tools that can provide real-time feedback on drug efficacy at target site to enable alteration in treatment regimens early during cancer therapy. Here, we report on theranostic optical imaging probes based on shortwave infrared (SWIR)-emitting rare earth-doped nanoparticles encapsulated with human serum albumin (abbreviated as ReANCs) that have demonstrated superior surveillance capability for detecting micro-lesions at depths of 1 cm in a mouse model of breast cancer metastasis. Most notably, ReANCs previously deployed for detection of multi-organ metastases resolved bone lesions earlier than contrast-enhanced magnetic resonance imaging (MRI). We engineered tumor-targeted ReANCs carrying a therapeutic payload as a potential theranostic for evaluating drug efficacy at the tumor site. In vitro results demonstrated efficacy of ReANCs carrying doxorubicin (Dox), providing sustained release of Dox while maintaining cytotoxic effects comparable to free Dox. Significantly, in a murine model of breast cancer lung metastasis, we demonstrated the ability for therapy monitoring based on measurements of SWIR fluorescence from tumor-targeted ReANCs. These findings correlated with a reduction in lung metastatic burden as quantified via MRI-based volumetric analysis over the course of four weeks. Future studies will address the potential of this novel class of theranostics as a preclinical pharmacological screening tool.
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影响因子：
12.4
作者：
An FF;Zhang XH
通讯作者：
Zhang XH
影响因子：
--
作者：
Abbasi S;Paul A;Shao W;Prakash S
通讯作者：
Prakash S
影响因子：
6
作者：
Bi D;Zhao L;Yu R;Li H;Guo Y;Wang X;Han M
通讯作者：
Han M
影响因子：
10.8
作者：
Janes, KA;Fresneau, MP;Alonso, MJ
通讯作者：
Alonso, MJ
影响因子：
4.8
作者：
Frei E
通讯作者：
Frei E