3D tumor tissue analogs and their orthotopic implants for understanding tumor-targeting of microenvironment-responsive nanosized chemotherapy and radiation

详细信息    查看全文

• 作者：Pallavi Sethi ; PhD^a ; Amar Jyoti ; PhD^a ; Elden P. Swindell ; PhD^b ; Ryan Chan ; PharmD^a ; Ulrich W. Langner ; DABR ; PhD^c ; Jonathan M. Feddock ; MD^c ; Radhakrishnan Nagarajan ; PhD^d ; Thomas V. O&rsquo ; Halloran ; PhD^b ; Meenakshi Upreti ; PhD^a ; ^{m.upreti@uky.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Tumor tissue analogs (TTA) ; Tumor cell spheroids ; Galectin-1 ; Tumor microenvironment ; Targeted nanoparticle ; 3D co-cultures ; 3 dimensional triple negative breast cancer (3D TNBC) model
• 刊名：Nanomedicine: Nanotechnology, Biology and Medicine
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：11
• 期：8
• 页码：2013-2023
• 全文大小：1996 K

文摘

An appropriate representation of the tumor microenvironment in tumor models can have a pronounced impact on directing combinatorial treatment strategies and cancer nanotherapeutics. The present study develops a novel 3D co-culture spheroid model (3D TNBC) incorporating tumor cells, endothelial cells and fibroblasts as color-coded murine tumor tissue analogs (TTA) to better represent the tumor milieu of triple negative breast cancer in vitro. Implantation of TTA orthotopically in nude mice, resulted in enhanced growth and aggressive metastasis to ectopic sites. Subsequently, the utility of the model is demonstrated for preferential targeting of irradiated tumor endothelial cells via radiation-induced stromal enrichment of galectin-1 using anginex conjugated nanoparticles (nanobins) carrying arsenic trioxide and cisplatin. Demonstration of a multimodal nanotherapeutic system and inclusion of the biological response to radiation using an in vitro/in vivo tumor model incorporating characteristics of tumor microenvironment presents an advance in preclinical evaluation of existing and novel cancer nanotherapies.

From the Clinical Editor

Existing in-vivo tumor models are established by implanting tumor cells into nude mice. Here, the authors described their approach 3D spheres containing tumor cells, enodothelial cells and fibroblasts. This would mimic tumor micro-environment more realistically. This interesting 3D model should reflect more accurately tumor response to various drugs and would enable the design of new treatment modalities.