Comparative effects of free doxorubicin, liposome encapsulated doxorubicin and liposome co-encapsulated alendronate and doxorubicin (PLAD) on the tumor immunologic milieu in a mouse fibrosarcoma model

Nanotheranostics

article

Rakibul Islam¹  Jalpa Patel¹  Patricia Ines Back¹  Hilary Shmeeda²  Konstantin Adamsky³  Hui Yang⁴  Carlos Alvarez⁴  Alberto A. Gabizon²  Ninh M. La-Beck¹ 

[1] Department of Immunotherapeutics and Biotechnology, Texas Tech University Health Sciences Center School of Pharmacy;Oncology Institute, Shaare Zedek Medical Center and Hebrew University-Faculty of Medicine;Levco Pharmaceuticals Ltd.;Department of Pharmacy Practice, Texas Tech University Health Sciences Center School of Pharmacy

关键词: chemotherapy;    immunotherapy;    nanomedicine;    bisphosphonate;    tumor-associated macrophages;    alendronate;    doxorubicin;    fibrosarcoma;   

DOI  :  10.7150/ntno.75045

学科分类：大气科学

来源: Ivyspring International Publisher

【 摘 要 】

Background: We have previously shown that alendronate, an amino-bisphosphonate, when reformulated in liposomes, can significantly enhance the efficacy of cytotoxic chemotherapies and help remodel the immunosuppressive tumor microenvironment towards an immune-permissive milieu resulting in increased anticancer efficacy. In addition, we have previously shown that the strong metal-chelating properties of alendronate can be exploited for nuclear imaging of liposomal biodistribution. To further improve anticancer efficacy, a pegylated liposome formulation co-encapsulating alendronate and doxorubicin (PLAD) has been developed. In this study, we examined the effects of PLAD on the tumor immunologic milieu in a mouse fibrosarcoma model in which the tumor microenvironment is heavily infiltrated with tumor-associated macrophages (TAM) that are associated with poor prognosis and treatment resistance.

【 授权许可】

CC BY-NC