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.
Keywords: Bispecific target delivery; Large breast tumor model; Lipid-coated calcium phosphate nanoparticles; Photothermal therapy; RNAi therapy.
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