(PQC5)Early Detection Pancreatic Cancer by Hyperpolarized Silicon Nanoparticles

(PQC5)超极化硅纳米颗粒早期检测胰腺癌

基本信息

项目摘要

DESCRIPTION (provided by applicant): The primary reason for a poor prognosis for patients with pancreatic cancer is because 80-90% of patients have unresectable disease at the time of diagnosis. This research proposal offers a strategy that may enable the detection of pancreatic cancer by MRI with at least two to three orders of magnitude smaller than those currently detected by employing target specific hyperpolarized silicon nanoparticles. This strategy when successfully introduced in the clinic will improve the overall detectability of pancreatic tumors a early stages of their development and could potentially save lives by successful surgical interventions. Among pancreatic tumor biomarkers produced in pancreatic tissue, the hepatocarcinoma-intestine-pancreas/pancreatitis- associated protein (HIP/PAP) was found to be over-expressed more than 130-fold in pancreatic acinar cells in pancreatic cancer, as compared to normal pancreas. In contrast, only a 9-fold increased expression of HIP/PAP protein was observed in acinar cells in chronic pancreatitis. This offers a unique opportunity to image the tumor and tumor stromal interaction in pancreatic cancer. The objective of this exploratory project is to develop a highly sensitive HIP/PAP targeted molecular imaging agent based on a novel silicon hyperpolarized Magnetic Resonance Imaging (MRI) technique recently developed in my laboratory. Previous biochemical studies demonstrated that HIP/PAP protein is a "lactose binding protein" which has a very high affinity to D- lactose. We intend to employ lactose-functionalized hyperpolarized Silicon nanoparticles (SiNPs) to target HIP/PAP protein in the acinar cells surrounding the pancreatic tumor. Hyperpolarization leads to over 10,000 fold signal enhancement compared to conventional MRI. We hypothesize that the specificity of lactose- functionalized SiNPs binding to HIP/PAP surrounding the pancreatic cancer coupled with the sensitivity gain due to hyperpolarization will lead to an "effective lesion size amplification", thereby, enabling the visualization of pancreatic carcinoma in in vivo MRI with at least two to three orders of magnitude smaller than those currently detected. Towards this goal, we propose the following three specific aims: I. Optimize the levels of hyperpolarization achievable by radical-free 29Si Dynamic Nuclear Polarization on lactose-functionalized silicon nanoparticles (SiNPs) as a function of SiNP size and in vivo targeting efficacy. II. Demonstrate "effective lesion size amplification" with real-time hyperpolarized MRI in a) one orthotropic pancreatic tumor xenograft mouse model and in b) two cohorts of patient derived tumor engrafted into NOD/SCID mice one of which is na¿ve human pancreatic tumor and the other exposed to neoadjuvant therapy. III. Correlate hyperpolarized 29Si MR data acquired in Aims II with immunohistochemistry and optical imaging data of fluorescently-tagged SiNPs in the murine cancer models demonstrating efficacy of this technique on the detection pancreatic carcinoma with at least two to three orders of magnitude smaller than those currently detected.
描述(由申请人提供):胰腺癌患者预后不良的主要原因是80-90%的患者在诊断时患有不可切除的疾病。这项研究提案提供了一种策略,可以通过MRI检测胰腺癌,其数量级比目前通过采用靶向特异性超极化硅纳米颗粒检测到的数量级小至少两到三个数量级。这种策略在临床上成功引入后,将提高胰腺肿瘤发展早期的整体可检测性,并可能通过成功的手术干预挽救生命。在胰腺组织中产生的胰腺肿瘤生物标志物中,发现与正常胰腺相比,肝癌-肠-胰腺/胰腺炎相关蛋白(HIP/PAP)在胰腺癌中的胰腺腺泡细胞中过表达超过130倍。相反,慢性胰腺炎的腺泡细胞中HIP/PAP蛋白的表达仅增加9倍。这为胰腺癌中肿瘤和肿瘤间质相互作用的成像提供了独特的机会。这个探索性项目的目的是开发一种高度敏感的HIP/PAP靶向分子成像剂的基础上,一种新的硅超极化磁共振成像(MRI)技术最近在我的实验室开发。以前的生化研究表明,HIP/PAP蛋白是一种“乳糖结合蛋白”,对D-乳糖具有很高的亲和力。我们打算采用乳糖功能化的超极化硅纳米粒子(SiNP)靶向胰腺肿瘤周围腺泡细胞中的HIP/PAP蛋白。与常规MRI相比,超极化导致超过10,000倍的信号增强。我们假设,乳糖官能化的SiNP结合胰腺癌周围的HIP/PAP的特异性与由于超极化引起的灵敏度增益相结合,将导致“有效的病变尺寸放大”,从而使得胰腺癌在体内MRI中的可视化比目前检测到的那些小至少两到三个数量级。为此,我们提出以下三个具体目标:优化乳糖功能化硅纳米颗粒(SiNP)上的无自由基29 Si动态核极化可实现的超极化水平,作为SiNP尺寸和体内靶向功效的函数。二.在a)一种正交各向异性胰腺肿瘤异种移植小鼠模型和B)移植到NOD/SCID小鼠中的两个患者源性肿瘤队列(其中一个是未处理的人胰腺肿瘤,另一个暴露于新辅助治疗)中,用实时超极化MRI证明“有效的病变大小放大”。三.将目标II中获得的超极化29 Si MR数据与小鼠癌症模型中荧光标记SiNP的免疫组织化学和光学成像数据相关联,证明该技术在检测胰腺癌方面的有效性,比目前检测到的胰腺癌小至少两到三个数量级。

项目成果

期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Pratip K. Bhattacharya其他文献

Potentiation of immune checkpoint blockade with a pH-sensitizer as monitored in two pre-clinical tumor models with acidoCEST MRI
在两项使用酸敏感磁共振成像(acidoCEST MRI)的临床前肿瘤模型中监测到的 pH 敏化剂对免疫检查点阻断的增强作用
  • DOI:
    10.1038/s41416-025-02962-1
  • 发表时间:
    2025-02-24
  • 期刊:
  • 影响因子:
    6.800
  • 作者:
    Renee L. Tran;Tianzhe Li;Jorge de la Cerda;F. William Schuler;Alia S. Khaled;Shivanand Pudakalakatti;Pratip K. Bhattacharya;Sanhita Sinharay;Mark D. Pagel
  • 通讯作者:
    Mark D. Pagel
Unlocking ferroptosis in prostate cancer — the road to novel therapies and imaging markers
解锁前列腺癌中的铁死亡——通向新型疗法和成像标志物的道路
  • DOI:
    10.1038/s41585-024-00869-9
  • 发表时间:
    2024-04-16
  • 期刊:
  • 影响因子:
    14.600
  • 作者:
    Pham Hong Anh Cao;Abishai Dominic;Fabiola Ester Lujan;Sanjanaa Senthilkumar;Pratip K. Bhattacharya;Daniel E. Frigo;Elavarasan Subramani
  • 通讯作者:
    Elavarasan Subramani
A pioneering artificial intelligence tool to predict treatment outcomes in ovarian cancer via diagnostic laparoscopy
一种开创性的人工智能工具,通过诊断性腹腔镜预测卵巢癌的治疗结果
  • DOI:
    10.1038/s41598-025-98434-w
  • 发表时间:
    2025-04-25
  • 期刊:
  • 影响因子:
    3.900
  • 作者:
    Xiaotian Ma;Yu-Chun Hsu;Amma Asare;Kai Zhang;Deanna Glassman;Katelyn F. Handley;Katherine Foster;Khwahish Sharma;Shannon Westin;Amir Jazaeri;Nicole D. Fleming;Pratip K. Bhattacharya;Xiaoqian Jiang;Anil K. Sood;Shayan Shams
  • 通讯作者:
    Shayan Shams

Pratip K. Bhattacharya的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Pratip K. Bhattacharya', 18)}}的其他基金

Targeted Hyperpolarized Molecular Beacons for Colorectal Cancer Detection
用于结直肠癌检测的靶向超极化分子信标
  • 批准号:
    10495268
  • 财政年份:
    2021
  • 资助金额:
    $ 17.4万
  • 项目类别:
Targeted Hyperpolarized Molecular Beacons for Colorectal Cancer Detection
用于结直肠癌检测的靶向超极化分子信标
  • 批准号:
    10696093
  • 财政年份:
    2021
  • 资助金额:
    $ 17.4万
  • 项目类别:
Targeted Hyperpolarized Molecular Beacons for Colorectal Cancer Detection
用于结直肠癌检测的靶向超极化分子信标
  • 批准号:
    10371429
  • 财政年份:
    2021
  • 资助金额:
    $ 17.4万
  • 项目类别:
(PQC5)Early Detection Pancreatic Cancer by Hyperpolarized Silicon Nanoparticles
(PQC5)超极化硅纳米颗粒早期检测胰腺癌
  • 批准号:
    8687422
  • 财政年份:
    2014
  • 资助金额:
    $ 17.4万
  • 项目类别:

相似海外基金

Regulation of acinar cell function
腺泡细胞功能的调节
  • 批准号:
    RGPIN-2018-06444
  • 财政年份:
    2022
  • 资助金额:
    $ 17.4万
  • 项目类别:
    Discovery Grants Program - Individual
Regulation of acinar cell function
腺泡细胞功能的调节
  • 批准号:
    RGPIN-2018-06444
  • 财政年份:
    2021
  • 资助金额:
    $ 17.4万
  • 项目类别:
    Discovery Grants Program - Individual
Regulation of acinar cell function
腺泡细胞功能的调节
  • 批准号:
    RGPIN-2018-06444
  • 财政年份:
    2020
  • 资助金额:
    $ 17.4万
  • 项目类别:
    Discovery Grants Program - Individual
Elucidation of the developmental mechanism of pancreatic acinar cell metaplasia in stomach
胃胰腺腺泡细胞化生发育机制的阐明
  • 批准号:
    20K16985
  • 财政年份:
    2020
  • 资助金额:
    $ 17.4万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Research on carcinogenesis and cell differentiation using established human pancreatic acinar cell carcinoma cell line
利用已建立的人胰腺腺泡细胞癌细胞系进行癌发生和细胞分化的研究
  • 批准号:
    19K07518
  • 财政年份:
    2019
  • 资助金额:
    $ 17.4万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Characterization of SPCA2C in acinar cell function
SPCA2C 在腺泡细胞功能中的表征
  • 批准号:
    539767-2019
  • 财政年份:
    2019
  • 资助金额:
    $ 17.4万
  • 项目类别:
    University Undergraduate Student Research Awards
Regulation of acinar cell function
腺泡细胞功能的调节
  • 批准号:
    RGPIN-2018-06444
  • 财政年份:
    2019
  • 资助金额:
    $ 17.4万
  • 项目类别:
    Discovery Grants Program - Individual
The study to detect early-stage pancreatic cancer based on the data from molecular biology about the atrophic acinar cell surrounding carcinoma in situ.
该研究基于原位癌周围萎缩性腺泡细胞的分子生物学数据来检测早期胰腺癌。
  • 批准号:
    18K07897
  • 财政年份:
    2018
  • 资助金额:
    $ 17.4万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Regulation of acinar cell function
腺泡细胞功能的调节
  • 批准号:
    RGPIN-2018-06444
  • 财政年份:
    2018
  • 资助金额:
    $ 17.4万
  • 项目类别:
    Discovery Grants Program - Individual
Investigation of the role of BRG1 in acinar cell-derived pancreatic tumorigenesis
BRG1 在腺泡细胞源性胰腺肿瘤发生中的作用研究
  • 批准号:
    17H06805
  • 财政年份:
    2017
  • 资助金额:
    $ 17.4万
  • 项目类别:
    Grant-in-Aid for Research Activity Start-up
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了