Cancer Chemistry最新文献_第4页

Abstract 309: Development of a multi-omic, pooled cancer cell screen for nanoparticle delivery 309:纳米颗粒递送的多组学、集合癌细胞筛选的开发

Cancer Chemistry Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-309

Joelle P. Straehla, Natalie Boehnke, M. Kocak, Melissa M Ronan, H. Safford, M. Rees, J. Roth, A. Koehler, P. Hammond

{"title":"Abstract 309: Development of a multi-omic, pooled cancer cell screen for nanoparticle delivery","authors":"Joelle P. Straehla, Natalie Boehnke, M. Kocak, Melissa M Ronan, H. Safford, M. Rees, J. Roth, A. Koehler, P. Hammond","doi":"10.1158/1538-7445.AM2021-309","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-309","url":null,"abstract":"Background: Nanoparticles (NPs) hold enormous promise for the targeted delivery of therapeutics for cancer, but clinical translation is lacking largely due to limited tumor accumulation. Tumor heterogeneity and NP complexity make it challenging to deconvolute individual factors that contribute to NP-cell interactions. To address this, we developed a competition assay leveraging 500 stably DNA-barcoded adherent cancer cell lines annotated with multi-omic data from the Broad Institute (PRISM cells) to investigate cell association patterns across a library of NPs. We hypothesize that simultaneous screening of hundreds of cancer cell lines will identify factors underlying differential NP-cancer cell interactions. Methods: We synthesized a library of 40 fluorescently-labeled NPs comprising clinical and experimental formulations. Clinical formulations included liposomal doxorubicin and irinotecan analogs and liposomal or poly(lactide-co-glycolide, PLGA) NPs with and without polyethylene glycol (PEG); these are either FDA-approved or in clinical trials. Experimental formulations included liposomal and PLGA cores electrostatically coated with a range of native and synthetic polymers as well as polystyrene NPs of varying sizes and surface chemistries. Fluorescent antibodies -in free form or NP-conjugated—were included as validation compounds. PRISM cells were pooled and incubated with NPs prior to fluorescence-activated cell sorting (FACS) to bin cells based on strength of NP association. After cell lysis, DNA barcodes were amplified and sequenced. Using appropriate controls to adjust for baseline barcode abundance, we generated an association score for each NP-cell line pair. Next, we performed multi-omic univariate analyses and applied a random forest algorithm to identify factors predictive of NP-cancer cell association. Results: After pooled screening of PRISM cells, we consistently identified cancer cell lines based on strength of NP-association across technical and biologic replicates. Using antibodies and antibody-conjugated NPs targeting epidermal growth factor receptor (EGFR), we identified EGFR gene and protein expression as highly significant hits, validating our ability to robustly identify relevant biomarkers. Additional hits were evaluated based on strength and direction of association to identify predictive biomarkers by formulation. We also employed k-means clustering to investigate hits across NP formulations, identifying highly interconnected protein association networks that elucidate likely mechanisms of NP-cancer cell association. Conclusions: We report a new pooled screening platform to investigate factors influencing NP-cancer cell interactions. We validated the screen by identifying known biomarkers, and also identified new predictive biomarkers that may pave the way for more effective nanotherapeutics. Citation Format: Joelle P. Straehla, Natalie Boehnke, Mustafa Kocak, Melissa Ronan, Hannah Safford, Matthew G. Rees, Jennifer A. R","PeriodicalId":9563,"journal":{"name":"Cancer Chemistry","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87538730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Abstract 317: Berberine-mediated reprogramming of the inflammatory environment in anaplastic thyroid cancer 摘要:小檗碱介导的间变性甲状腺癌炎症环境重编程

Cancer Chemistry Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-317

T. Jarboe, N. Desouza, Sarnath Singh, A. Moscatello, J. Geliebter, R. Tiwari, Xiu-Min Li

引用次数: 0

Abstract 307: Lymph node accumulation of theranostic lipid-based nanoparticles in healthy and diseased models: Preliminary results comparing nanoparticle morphology and targeting 摘要307:治疗性脂基纳米颗粒在健康和患病模型中的淋巴结积聚:纳米颗粒形态和靶向性的初步结果比较

Cancer Chemistry Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-307

M. Valic, Mark Zheng, L. Ding, Michelle Lai, Chris J. Zhang, T. Ye, Jenny Ma, M. Halim, P. Schimmer, Wenlei Jiang, Juan Chen, G. Zheng

{"title":"Abstract 307: Lymph node accumulation of theranostic lipid-based nanoparticles in healthy and diseased models: Preliminary results comparing nanoparticle morphology and targeting","authors":"M. Valic, Mark Zheng, L. Ding, Michelle Lai, Chris J. Zhang, T. Ye, Jenny Ma, M. Halim, P. Schimmer, Wenlei Jiang, Juan Chen, G. Zheng","doi":"10.1158/1538-7445.AM2021-307","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-307","url":null,"abstract":"Background: Accumulation of systemically administered nanoparticles (NPs) in lymph nodes has been exploited clinically for diagnostic imaging (e.g., USPIOs for lymph node metastasis) and therapeutic applications (e.g., vaccine delivery). However, the combination of diagnostic and therapeutic functionalities into a single theranostic NP has obliged undesirable trade-offs between either the imaging or drug delivery of the NP and their specific accumulation in lymph nodes. To overcome these trade-offs, we conducted a screen of various lipid-based theranostic NPs focusing on differing NP design and their resulting pharmacokinetic behaviours in healthy and diseased lymph node models. Methods: Lipid-based theranostic NPs with varying physicochemical characteristics (e.g., formulation, size and morphology, surface targeting, etc.) were prepared with positron emitting Cu-64 and administered systemically at equivalent NP doses in healthy and diseased rodent models (i.e., mice and rats). NP types were assessed for time-dependent accumulation in major lymph node basins via non-invasive whole-body PET/MR imaging at two or more timepoints per animal. 72-hours post-injection the animals were sacrificed, and lymph nodes and major organs were excised for gamma counting and pathological evaluation. Pharmacokinetic behaviour of NPs in healthy versus diseased lymph nodes were calculated in individual animals and in naively pooled datasets using non-compartmental analysis. Results: Preliminary analysis identified a leading NP candidate with specific lymph node targeting in healthy and diseased rodents: a discoidal, 35-nm peptide-targeted HDL-mimetic. In comparison with a spherical, 100-nm PEGylated NP, the discoidal NP obtained greater absolute (%ID) and relative (%ID/g) amounts of injected dose in anatomically matched lymph nodes than the spherical NP, regardless of lymph node pathology. At greatest measured concentration in healthy lymph nodes, typically 24-hpi, the differences between the discoidal and spherical NPs were on average 3-fold greater (2.893 vs. 0.864, %ID/g). Differences in other pharmacokinetic parameters such as AUC (%ID/g*h) and MRT (h) were equally pronounced. Conclusions: Our preliminary analysis uncovered a discoidal, peptide-targeted HDL-mimetic with remarkable accumulation in lymph nodes of healthy and diseased models. Future investigations will focus on the biochemical and cellular mechanisms underlying their unique lymphatic pharmacokinetics. These preliminary results provide key insights for design of theranostic NPs for non-invasive imaging and staging lymph node pathologies, and for applications in delivery of therapeutics to lymph nodes following systemic administration. Citation Format: Michael S. Valic, Mark Zheng, Lili Ding, Michelle Lai, Chris J. Zhang, Tina Ye, Jenny Ma, Michael Halim, Pamela Schimmer, Wenlei Jiang, Juan Chen, Gang Zheng. Lymph node accumulation of theranostic lipid-based nanoparticles in healthy and diseased model","PeriodicalId":9563,"journal":{"name":"Cancer Chemistry","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86994537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Abstract 266: Differential collective cell migratory behaviors modulated by phospholipid nanoparticles 266:磷脂纳米颗粒调控的差异集体细胞迁移行为

Cancer Chemistry Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-266

Kenry, Bin Liu

引用次数: 0

Abstract 15: Confirmatory integrated proteogenomic characterization of clear cell renal cell carcinoma 摘要:透明细胞肾细胞癌的验证性综合蛋白质基因组学特征

Cancer Chemistry Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-15

D. Clark, Yize Li

引用次数: 0

Abstract 292: A dual CTLA4 and PD1 microbially derived inhibitor shows efficacy in anti-PD1 mAb unresponsive tumor models through a unique allosteric mechanism of action

Cancer Chemistry Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-292

G. Gutierrez, T. Phares, V. Kotraiah, P. Buontempo, James Pannucci, L. Keltner

引用次数: 0

Abstract 303: Surface modification of paclitaxel-loaded nanoparticles based on polydopamine with pH sensitive property for targeted therapy in hepatocellular carcinoma 摘要303:基于pH敏感特性的聚多巴胺负载紫杉醇纳米粒子表面修饰用于肝癌靶向治疗

Cancer Chemistry Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-303

Mingfang Wu, Xinming Xia, Danna Sun, Chen Zhong

{"title":"Abstract 303: Surface modification of paclitaxel-loaded nanoparticles based on polydopamine with pH sensitive property for targeted therapy in hepatocellular carcinoma","authors":"Mingfang Wu, Xinming Xia, Danna Sun, Chen Zhong","doi":"10.1158/1538-7445.AM2021-303","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-303","url":null,"abstract":"Drug-loaded nanocarrier is a promising treatment for targeted therapy in hepatocellular carcinoma (HCC) due to their sustained release and outstanding tumor-targeting properties. Nevertheless, a limitation of current nanocarriers is the contradiction between multiple functions and favorable biocompatibility, owing to most of functional substances are non-biological. In this study, we introduced a targeting arginine-glycine-aspartic acid (RGD)-peptide on the surface of polydopamine (PDA)-ploy (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) to develop a novel nanoparticle, which were employed as a drug delivery system loaded with paclitaxel (PTX) for HCC therapy. Paclitaxel-loaded PHBV nanoparticles (PHBV-PTX-NPs) were prepared by emulsion solvent evaporation. As a gatekeeper, the pH-sensitive coating was formed by self-polymerization of dopamine. The RGD and PDA coated nanoparticles were combined through the Michael addition. The chemical structures and properties of these nanoparticles were characterized by dynamic light scattering-autosizer, transmission electron microscope, fourier transform infrared spectroscopy, differential scanning calorimetry, thermogravimetry and X-ray photoelectron spectroscopy. As expected, these RGD-PDA-PHBV-PTX-NPs achieved excellent targeting efficiency, which was revealed by the cellular uptake and cytotoxicity assay in HCC cells. Compared with that of free PTX, the RGD-PDA-PHBV-PTX-NPs showed more superior antitumor efficacy in the xenograft mouse model. Notably, in addition to efficient anticancer activities, RGD-PDA-PHBV-PTX-NPs exhibited lower toxicity than PTX to normal hepatocytes and mouse in vitro and in vivo, respectively. These studies suggest the potential beneficial use of RGD-PDA-PHBV-PTX-NPs in future HCC-targeted therapy with drug-loaded nanocarriers. Citation Format: Mingfang Wu, Xinming Xia, Danna Sun, Chen Zhong. Surface modification of paclitaxel-loaded nanoparticles based on polydopamine with pH sensitive property for targeted therapy in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 303.","PeriodicalId":9563,"journal":{"name":"Cancer Chemistry","volume":"469 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76808368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Abstract 304: Peptide-mediated delivery of siRNAs targeting CSNK2A1 decreases migration of ovarian cancer cellsin vitro 摘要:肽介导的靶向CSNK2A1的sirna在体外可减少卵巢癌细胞的迁移

Cancer Chemistry Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-304

A. Hazelton, T. Samec, J. Boulos, S. Gilmore, Angela A Alexander-Bryant

引用次数: 0

Abstract 280: Sub-30-nm capsules for drug delivery 280:用于给药的亚30nm胶囊

Cancer Chemistry Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-280

Xiaowei Ma, Ping Zhang, Chao Cui, Chang-Chun Ling, Lina Cui

{"title":"Abstract 280: Sub-30-nm capsules for drug delivery","authors":"Xiaowei Ma, Ping Zhang, Chao Cui, Chang-Chun Ling, Lina Cui","doi":"10.1158/1538-7445.AM2021-280","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-280","url":null,"abstract":"Systemic treatment of cancer using long-circulating nanomedicines is promising due to their passive tumor targeting ability to achieve higher and more selective accumulation in tumors with irregular vascularization, a phenomenon known as extended permeation and retention (EPR) effect.1,2 Clinical use of nanometer-sized carriers, such as Doxil and Abraxane, to deliver chemotherapeutics to solid tumors is proven effective in highly vascularized tumors such as breast cancer, ovarian cancer, multiple myeloma, and Kaposi9s sarcoma.3-5 Most nanomedicines that are being developed or approved so far have a diameter of around 100-200 nm for prolonged retention in highly angiogenic and densely vascularized tumors,6 however, they suffer from limited accumulation and poor penetration to the inner core of avascular or hypovascular tumors (such as prostate and pancreatic cancer),7-9 therefore nanomedicines small than 100 nm are more preferred for improved tumor penetration.10,11 Here we present our strategy to form cyclodextrin-based sub-30-nm nanocarriers, which allows easy drug encapsulation, and successful delivery of therapeutics to human tumor xenografts with significantly reduced tumor growth rates and improved survival rates. Citation Format: Xiaowei Ma, Ping Zhang, Chao Cui, Chang-Chun Ling, Lina Cui. Sub-30-nm capsules for drug delivery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 280.","PeriodicalId":9563,"journal":{"name":"Cancer Chemistry","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74226789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Abstract 273: A mass spectrometry survey of frequent HLA alleles successfully presenting common tumor specific mutations for immune recognition 摘要273:一项常见HLA等位基因的质谱调查成功地提出了常见的肿瘤特异性突变，用于免疫识别

Cancer Chemistry Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-273

Catherine M. Ade, Y. Qi, Sudipto Das, K. Hanada, Tapan Maity, Xu Zhang, T. Andresson, U. Guha, J. Yang

引用次数: 0