Biodegradable hollow CuS nanoparticles for photothermal cancer therapy

描述（由申请人提供）：光热消融（PTA）治疗为无法手术的肿瘤提供了微创治疗。纳米颗粒如金纳米结构，沿着具有强光热耦合效应，已被证明可以大大增强PTA的功效。另一方面，目前使用的PTA具有几个局限性，例如在治疗转移性癌症方面的效果较差;纳米颗粒的不可生物降解性，以及纳米颗粒向灌注不良的肿瘤部位中的肿瘤组织中的限制性运输。的 限制性转运可能导致亚致死剂量的热传递，并可能导致肿瘤复发和产生耐药性。空心硫化铜纳米粒子（HCuSNPs）是一类新型的光热纳米粒子。如我们的初步研究所示，与金类似物相比，HCuSNP是可生物降解的，并通过肾脏消除。我们假设HCuSNPs为控制肿瘤复发和转移提供了先进的多模式光热治疗方法。本项目的具体目标是：（1）评估HCuSNPs的代谢和毒性;（2）开发HCuSNPs介导的癌症光热治疗多阶段递送;（3）探索HCuSNPs佐剂介导的原位光免疫治疗（ISPI）。在目的1中，我们将检查PEG-HCuSNP的细胞命运和代谢;并分析PEG-HCuSNP的单次和重复剂量毒性。目的二：利用光声成像技术分析HCuSNPs在小鼠肿瘤异种移植模型中的肿瘤递送阶段，并通过多阶段递送验证PTA的效果。在目标3中，我们将评估由HCuSNP佐剂介导的ISPI诱导的免疫应答;并评估局部和远端抗肿瘤作用。这些研究将在异种移植、同种异体移植和自发性乳腺癌模型中进行。在世界范围内，乳腺癌是第二个最常见的女性恶性肿瘤。成功验证所提出的多模式PTA将提供一个重要的治疗策略，不仅对原发性，而且对转移性乳腺癌。显然，这项技术，结合使用光纤，可以 可用于治疗多种癌症，甚至是深层组织的癌症。

DESCRIPTION (provided by applicant): Photothermal ablation (PTA) therapy provides a minimally invasive treatment for inoperable tumors. Nanoparticles such as gold nanostructures, along with strong photothermal coupling effect, have been shown to greatly enhance the efficacy of PTA. On the other hand, currently used PTA has several limitations such as less effectiveness in treating metastatic cancer; non-biodegradability of the nanoparticles, and restrictive transport of nanoparticles into tumor interstitium in a poorly perfused tumor site. The restrictive transport likely results in sublethal dose of heat transfer and may cause tumor recurrence and develop resistance. Hollow CuS nanoparticles (HCuSNPs) belong to a new class of photothermal nanoparticles. As shown in our Preliminary Study, HCuSNPs, in contrast to gold analogs, were biodegradable and eliminated through the kidney. We hypothesize that the HCuSNPs provide advanced multimodality photothermal therapeutic approaches for control of tumor recurrence and metastases. The Specific Aims of this project are: (1) to evaluate metabolism and toxicity of HCuSNPs; (2) to develop HCuSNPs-mediated multistage delivery for cancer photothermal therapy; and (3) to explore HCuSNPs-adjuvant-mediated in situ photoimmunotherapy (ISPI). In Aim 1, we will examine the cellular fate and metabolism of the PEG-HCuSNPs; and analyze single and repeated dose toxicity of the PEG-HCuSNPs. In Aim 2, we will use photoacoustic imaging to analyze the stages of tumor delivery of HCuSNPs in mouse tumor xenograft model; and validate the effect of PTA through the multistage delivery. In Aim 3, we will assess the immune response induced by HCuSNPs-adjuvant-mediated ISPI; and evaluate the local and distal anti-tumor effect. These studies will be performed in xenograft, allograft and spontaneous models of breast cancer. Worldwide, breast cancer is the second most frequently diagnosed malignancy in women. A success in validating the proposed multimodality PTA will provide an important therapeutic strategy not only for primary but also for metastatic breast cancer. Clearly, this technology, in combination with the use of fiberoptics, can be used to treat a broad range of cancers even in deep tissues.