Biodegradable hollow CUS nanoparticles for photothermal cancer therapy

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，加上强烈的光热耦合效应，已经被证明是 大大增强了PTA的功效。另一方面，目前使用的PTA具有以下几个局限性 治疗转移性癌症的有效性；纳米粒的非生物降解性，以及限制转移 纳米颗粒进入肿瘤间质中的肿瘤组织中，肿瘤组织的血流灌注较差。限制运输可能会导致 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为控制疾病提供先进的多模式光热治疗方法 肿瘤复发和转移的风险。本项目的具体目标是：(1)评价新陈代谢和毒性 HCuSNPs的研究；(2)开发HCuSNPs介导的癌症光热治疗的多阶段递送；以及(3) 探索HCuSNPs佐剂介导的原位光免疫治疗(ISPI)。在目标1中，我们将研究细胞 聚乙二醇单核苷酸和多聚乙醇单核苷酸重复给药的毒性。 HCuSNPs。在目标2中，我们将使用光声成像来分析HCuSNPs在肿瘤中的传递阶段。 建立小鼠肿瘤移植模型，并通过多阶段给药验证PTA的作用。在《目标3》中，我们将 评估HCuSNPs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房模型中进行。 癌症。在世界范围内，乳腺癌是女性第二常见的恶性肿瘤。在……方面取得成功 验证所提出的多模式PTA不仅将为原发和 也适用于转移性乳腺癌。显然，这种技术与光纤光学的使用相结合，是可以使用的 治疗范围广泛的癌症，甚至是深层组织的癌症。

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.