Antifouling Dendrimer-Entrapped Copper Sulfide Nanoparticles Enable Photoacoustic Imaging-Guided Targeted Combination Therapy of Tumors and Tumor Metastasis
Zhijun Ouyang, Canbing Li, Zhijuan Xiong, Cong Song, Yue Gao, Renna Liu, Mingwu Shen, Xiangyang Shi
Abstract
The development of functional intelligent theranostic nanoplatform for imaging-directed synchronous inhibition of primary tumor and tumor metastasis is still a challenging task. We present here the creation of functional dendrimer-entrapped CuS nanoparticles (CuS DENPs) complexed with plasmid DNA-encoding hypermethylation in cancer 1 (pDNA-HIC1) for photoacoustic (PA) imaging-directed simultaneous inhibition of tumors and tumor metastasis. Poly(amidoamine) dendrimers of generation 5 were covalently attached with 1,3-propane sultone and arginine-glycine-aspartic acid (RGD) peptide through a spacer of poly(ethylene glycol) and adopted for the templated synthesis of CuS NPs. The prepared functional RGD-CuS DENPs possess a mean CuS core diameter of 4.2 nm, good colloidal stability, and an excellent absorption feature in the second near-infrared window, thus having a photothermal conversion efficiency of 49.8% and an outstanding PA imaging capability. The functional DENPs can effectively deliver pDNA-HIC1 to prevent cancer cell invasion and metastasis in a serum-enhancing manner by virtue of zwitterionic modification-rendered antifouling property. The developed RGD-CuS DENPs/pDNA polyplexes display αvβ3 integrin-targeted enhanced anticancer activity through the combined CuS NP-mediated photothermal therapy (PTT) and pDNA delivery-rendered cancer cell metastasis inhibition. This can also be proven by the therapeutic efficacy of a triple-negative breast cancer model in vivo, where inhibition of both the primary subcutaneous tumor and lung metastasis can be realized. The created dendrimer-CuS hybrid nanoplatform represents one of the updated designs of nanomedicine for PA imaging-directed combination PTT/gene therapy of tumors and tumor metastasis.