Polydopamine-Coated Laponite Nanoplatforms for Photoacoustic Imaging-Guided Chemo-Phototherapy of Breast Cancer.

Theranostic nanoplatforms combining photosensitizers and anticancer drugs have aroused wide interest due to the real-time photoacoustic (PA) imaging capability and improved therapeutic efficacy by the synergistic effect of chemotherapy and phototherapy. In this study, polydopamine (PDA) coated laponite (LAP) nanoplatforms were synthesized to efficiently load indocyanine green (ICG) and doxorubicin (DOX), and modified with polyethylene glycol-arginine-glycine-aspartic acid (PEG-RGD) for PA imaging-guided chemo-phototherapy of cancer cells overexpressing αvß3 integrin. The formed ICG/LAP-PDA-PEG-RGD/DOX nanoplatforms showed significantly higher photothermal conversion efficiency than ICG solution and excellent PA imaging capability, and could release DOX in a pH-sensitive and NIR laser-triggered way, which is highly desirable feature in precision chemotherapy. In addition, the ICG/LAP-PDA-PEG-RGD/DOX nanoplatforms could be uptake by cancer cells overexpressing αvß3 integrin with high specificity, and thus serve as a targeted contrast agent for in vivo PA imaging of cancer. In vivo experiments with 4T1 tumor-bearing mouse model demonstrated that ICG/LAP-PDA-PEG-RGD/DOX nanoplatforms exhibited much stronger therapeutic effect and higher survival rate than monotherapy due to the synergetic chemo-phototherapy under NIR laser irradiation. Therefore, the reported ICG/LAP-PDA-PEG-RGD/DOX represents a promising theranostic nanoplatform for high effectiveness PA imaging-guided chemo-phototherapy of cancer cells overexpressing αvß3 integrin.

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

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.

Multifunctional Core-Shell Tecto Dendrimers Incorporated with Gold Nanoparticles for Targeted Dual Mode CT/MR Imaging of Tumors.

Development of multifunctional nanoprobes with an excellent imaging performance for precision tumor imaging still remains a great challenge. Here, we report the creation of multifunctional core-shell tecto dendrimers (CSTDs) incorporated with gold nanoparticles (Au NPs) as a platform for dual-mode computed tomography (CT)/magnetic resonance (MR) imaging of tumors. In this work, ß-cyclodextrin (CD)-modified generation 5 poly(amidoamine) (PAMAM) dendrimers were synthesized and entrapped with Au NPs as the core. Then, adamantine (Ad)-modified generation 3 PAMAM dendrimers acted as a shell to form Au NP-entrapped CSTDs (for short, Au CSTDs) through supramolecular host-guest recognition between CD and Ad. The formed Au CSTDs were sequentially modified with Arg-Gly-Asp (RGD) peptide through a spacer of polyethylene glycol (PEG), Gd chelator, and 1,3-propane sultone, followed by chelating Gd (III) ions. The synthesized multifunctional Au CSTDs with a mean size of 11.61 nm possess good colloidal stability, high X-ray attenuation property and high r1 relaxivity (9.414 mM-1 s-1), good antifouling property, and desired cytocompatibility. Due to the RGD-mediated targeting specificity to αvß3 integrin-overexpressing cancer cells, the multifunctional Au CSTDs enable targeted CT/MR dual mode imaging of a breast cancer model in vivo and can be cleared out of body through metabolization pathway with good biosafety profile. The developed multifunctional CSTDs may be applied as an effective CT/MR dual mode imaging probe for accurate diagnosis of various αvß3 integrin-overexpressing cancer types.