Multifunctional lipid-coated calcium phosphate nanoplatforms for complete inhibition of large triple negative breast cancer via targeted combined therapy

• Published in: Biomaterials Vol. 216; p. 119232
• Main Authors: Tang, Jie, Li, Bei, Howard, Christopher B., Mahler, Stephen M., Thurecht, Kristofer J., Wu, Yilun, Huang, Leaf, Xu, Zhi Ping
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.09.2019
• Subjects: Bispecific target delivery; Large breast tumor model; Lipid-coated calcium phosphate nanoparticles; Photothermal therapy; RNAi therapy; Photothermal therapy; Large breast tumor model; Lipid-coated calcium phosphate nanoparticles; RNAi therapy; Bispecific target delivery
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2019.119232

Combined and targeted therapy have been extensively employed to achieve more effective elimination of tumor tissues. In this study, biocompatible multifunctional lipid-coated calcium phosphate nanoparticles (LCP NPs) were designed and constructed as an efficient targeted delivery system for combined gene/photothermal therapy to inhibit growth of the triple negative breast tumor (MDA-MB-468) in vitro and in vivo. LCP NPs were functionalized with a bispecific antibody (BsAb) via non-covalent bond specific for methoxy group of PEG (mPEG) on the particle surface. This BsAb is also able to target epidermal growth factor receptor (EGFR) expressed on MDA-MB-468 cells. Such LCP-BsAb NPs loaded with Cell Death (CD)-siRNA and indocyanine green (ICG) were efficiently taken up by MDA-MB-468 cells, significantly inducing cell apoptosis and synergistically suppressing cell proliferation upon irradiation of 808 nm near-infrared laser. These targeted multifunctional LCP NPs more efficiently accumulated in the tumor tissue. The combined RNAi (CD-siRNA) and photothermal (ICG) therapy using the targeted LCP NPs nearly eliminated both small tumors (∼100 mm3) and large tumors (∼500 mm3) in the mouse model. Thus, the well-devised multifunctional LCP NPs are one of the most promising delivery systems for combined and targeted cancer therapy.