Antifouling Dendrimer-Entrapped Copper Sulfide Nanoparticles Enable Photoacoustic Imaging-Guided Targeted Combination Therapy of Tumors and Tumor Metastasis.

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 αvß3 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.