Biodegradable hollow CuS nanoparticles for photothermal cancer therapy

项目摘要 光热消融(PTA)为不能手术的肿瘤提供了一种微创治疗方法。 纳米粒子，如金纳米结构，以及强烈的光热耦合效应，已经被展示出来 以大大提高PTA的疗效。另一方面，当前使用的PTA有几个限制，例如 治疗转移性癌症的效果较差；纳米粒的不可生物降解性，以及限制性 将纳米颗粒运送到肿瘤组织中的肿瘤间质中，肿瘤组织的血流灌注不足。限制运输很可能 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。中空CuS 纳米颗粒(HCuSNPs)是一类新型的光热纳米颗粒。正如在我们的初步报告中所示 研究发现，与黄金类似物相比，HCuSNPs是可生物降解的，并可通过肾脏消除。我们 假设HCuSNPs提供了先进的多模式光热治疗方法 控制肿瘤复发和转移。本项目的具体目标是：(1)评估新陈代谢 以及HCuSNPs的毒性；(2)开发HCuSNPs介导的肿瘤光热多阶段递送 探索HCuSNPs佐剂介导的原位光免疫治疗(ISPI)。在目标1中，我们将 检测聚乙二醇HCuSNPs的细胞命运和代谢；分析单次和多次给药的毒性 聚乙二醇HCuSNPs。在目标2中，我们将使用光声成像来分析肿瘤交付的阶段 小鼠肿瘤移植瘤模型中的HCuSNPs；并通过多阶段递送验证PTA的作用。在……里面 目的3，评价HCuSNPs佐剂介导的ISPI诱导的免疫应答； 局部和远端抗肿瘤作用。这些研究将在异种移植、同种异体移植和自体移植中进行。 乳腺癌的模型。在世界范围内，乳腺癌是#年第二常见的恶性肿瘤。 女人。成功验证所提出的多模式PTA将提供一个重要的治疗策略 不仅适用于原发乳腺癌，也适用于转移性乳腺癌。显然，这项技术，结合使用 作为光纤的一部分，可用于治疗多种癌症，甚至是深层组织中的癌症。

Project Summary 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.