Dataset Information

Sequential Modulations of Tumor Vasculature and Stromal Barriers Augment the Active Targeting Efficacy of Antibody-Modified Nanophotosensitizer in Desmoplastic Ovarian Carcinoma.

ABSTRACT: Active-targeted nanoparticles are attractive carriers due to their potentials to facilitate specific delivery of drugs into tumor cells while sparing normal cells. However, the therapeutic outcomes of active-targeted nanomedicines are hampered by the multiple physiological barriers in the tumor microenvironment (TME). Herein, an epidermal growth factor receptor-targeted ultra-pH-sensitive nanophotosensitizer is fabricated, and the regulation of the TME to augment the active targeting ability and therapeutic efficacy is pinpointed. The results reveal that tumor vasculature normalization with thalidomide indiscriminately enhance the tumor accumulation of passive and active targeted nanoparticles, both of which are sequestered in the stromal bed of tumor mass. Whereas, photoablation of stromal cells located in perivascular regions significantly improves the accessibility of antibody-modified nanophotosensitizer to receptor-overexpressed cancer cells. After sequential regulation of TME, the antitumor efficacy of antibody-modified nanophotosensitizer is drastically enhanced through synergistic enhancements of tumor accumulation and cancer cell accessibility of active-targeted nanoparticles. The study offers deep insights about the intratumoral barriers that hinder the active-targeted nanoparticles delivery, and provides a basis for developing more effective strategies to accelerate the clinical translation of active-targeted nanomedicines.

SUBMITTER: Yan Y

PROVIDER: S-EPMC7856881 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Sequential Modulations of Tumor Vasculature and Stromal Barriers Augment the Active Targeting Efficacy of Antibody-Modified Nanophotosensitizer in Desmoplastic Ovarian Carcinoma.

Yan Yue Y Chen Binlong B Wang Zenghui Z Yin Qingqing Q Wang Yaoqi Y Wan Fangjie F Mo Yulin Y Xu Bo B Zhang Qiang Q Wang Siling S Wang Yiguang Y

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20201223 3

Active-targeted nanoparticles are attractive carriers due to their potentials to facilitate specific delivery of drugs into tumor cells while sparing normal cells. However, the therapeutic outcomes of active-targeted nanomedicines are hampered by the multiple physiological barriers in the tumor microenvironment (TME). Herein, an epidermal growth factor receptor-targeted ultra-pH-sensitive nanophotosensitizer is fabricated, and the regulation of the TME to augment the active targeting ability and ...[more]

PMID: 33552856

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Project description:Epithelial tissues have sparse stroma, in contrast to their corresponding tumours. The effect of cancer cells on stromal cells is well recognized. Increasingly, stromal components, such as endothelial and immune cells, are considered indispensable for cancer progression. The role of desmoplastic stroma, in contrast, is poorly understood. Targeting such cellular components within the tumour is attractive. Recent evidence strongly points towards a dynamic stromal cell participation in cancer progression that impacts patient prognosis. The role of specific desmoplastic stromal cells, such as stellate cells and myofibroblasts in pancreatic, oesophageal and skin cancers, was studied in bio-engineered, physiomimetic organotypic cultures and by regression analysis. For pancreatic cancer, the maximal effect on increasing cancer cell proliferation and invasion, as well as decreasing cancer cell apoptosis, occurs when stromal (pancreatic stellate cells) cells constitute the majority of the cellular population (maximal effect at a stromal cell proportion of 0.66-0.83), accompanied by change in expression of key molecules such as E-cadherin and ?-catenin. Gene-expression microarrays, across three tumour types, indicate that stromal cells consistently and significantly alter global cancer cell functions such as cell cycle, cell-cell signalling, cell movement, cell death and inflammatory response. However, these changes are mediated through cancer type-specific alteration of expression, with very few common targets across tumour types. As highlighted by these in vitro data, the reciprocal relationship of E-cadherin and polymeric immunoglobulin receptor (PIGR) expression in cancer cells could be shown, in vivo, to be dependent on the stromal content of human pancreatic cancer. These studies demonstrate that context-specific cancer-stroma crosstalk requires to be precisely defined for effective therapeutic targeting. These data may be relevant to non-malignant processes where epithelial cells interact with stromal cells, such as chronic inflammatory and fibrotic conditions.

Dataset Information

Sequential Modulations of Tumor Vasculature and Stromal Barriers Augment the Active Targeting Efficacy of Antibody-Modified Nanophotosensitizer in Desmoplastic Ovarian Carcinoma.

Publications

Sequential Modulations of Tumor Vasculature and Stromal Barriers Augment the Active Targeting Efficacy of Antibody-Modified Nanophotosensitizer in Desmoplastic Ovarian Carcinoma.

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