Development of multifunctional theranostic nanoplatforms with improved diagnostic sensitivity and therapeutic efficiency of tumors still remains a great challenge. A unique multifunctional theranostic nanoplatform based on generation 5 (G5) poly(amidoamine) dendrimer–stabilized gold nanoflowers (NFs) embedded with ultrasmall iron oxide (USIO) nanoparticles (NPs) for multimode T
1‐weighted magnetic resonance (MR)/computed tomography (CT)/photoacoustic (PA) imaging–guided combination photothermal therapy (PTT) and radiotherapy (RT) of tumors is reported here. G5 dendrimer–stabilized Au NPs and citric acid–stabilized USIO NPs are separately prepared, the two particles under a certain Fe/Au molar ratio are mixed to form complexes, the complexes are exposed to Au growth solution to form NFs via a seed–mediated manner, and the remaining dendrimer terminal amines are acetylated. The formed dendrimer‐stabilized Fe3O4/Au NFs (for short, Fe3O4/Au DSNFs) have a mean diameter of 99.8 nm, display good colloidal stability and cytocompatibility, and exhibit a near‐infrared absorption feature. The unique structure and composition of the Fe3O4/Au DSNFs endows them with a high r
1 relaxivity (3.22 mM−1 s−1) and photothermal conversion efficiency (82.7%), affording their uses as a theranostic nanoplatform for multimode MR/CT/PA imaging and combination PTT/RT of tumors with improved therapeutic efficacy, which is important for translational nanomedicine applications.
Development of versatile nanomaterials combining diagnostic and therapeutic functionalities within one single nanoplatform is extremely important for tumor theranostics. In this work, the authors report the synthesis of a gold nanostar (Au NS)-based theranostic platform stabilized with cyclic arginine-glycine-aspartic (Arg-Gly-Asp, RGD) peptide-modified amine-terminated generation 3 poly(amidoamine) dendrimers. The formed RGD-modified dendrimer-stabilized Au NSs (RGD-Au DSNSs) are used as a gene delivery vector to complex small interfering RNA (siRNA) for computed tomography (CT) imaging, thermal imaging, photothermal therapy (PTT), and gene therapy of tumors. The results show that the RGD-Au DSNSs are able to compact vascular endothelial growth factor siRNA and specifically deliver siRNA to cancer cells overexpressing α β integrin. Under near-infrared laser irradiation, the viability of cancer cells is only 20.2% after incubation with the RGD-Au DSNS/siRNA polyplexes, which is much lower than that of cells after single PTT or gene therapy treatment. Furthermore, in vivo results show that the RGD-Au DSNS/siRNA polyplexes enable tumor CT imaging, thermal imaging, PTT, and gene therapy after intratumoral injection. These results indicate that the developed multifunctional nanoconstruct is a promising platform for tumor imaging and combinational PTT and gene therapy.
We report the synthesis and characterization of antifouling zwitterion carboxybetaine acrylamide (CBAA)-modified dendrimer-entrapped gold nanoparticles (Au DENPs) for enhanced CT imaging applications. The CBAA-modified nanodevice displays a better protein resistance property, less macrophage cellular uptake and liver accumulation, and longer blood half-delay time than the PEGylated counterpart material, thereby enabling enhanced blood pool, lymph node, and tumor CT imaging.
Design of novel nanoplatforms with single imaging elements for dynamic and enhanced T1/T2‐weighted magnetic resonance (MR) imaging of diseases still remains significantly challenging. Here, a facile strategy to synthesize light‐addressable ultrasmall Fe3O4 nanoparticles (NPs) that can form nanoclusters (NCs) under laser irradiation for enhanced and dynamic T1/T2‐weighted MR imaging of inflammatory arthritis is reported. Citric acid‐stabilized ultrasmall Fe3O4 NPs synthesized via a solvothermal approach are linked with both the arthritis targeting ligand folic acid (FA) and light‐addressable unit diazirine (DA) via polyethylene glycol (PEG) spacer. The formed ultrasmall Fe3O4‐PEG‐(DA)‐FA NPs are cytocompatible, display FA‐mediated targeting specificity to arthritis‐associated macrophage cells, and can form NCs upon laser irradiation to have tunable r1 and r2 relaxivities by varying the laser irradiation duration. With these properties owned, the designed Fe3O4‐PEG‐(DA)‐FA NPs can be used for T1‐weighted MR imaging of arthritis without lasers and enhanced dual‐mode T1/T2‐weighted MR imaging of arthritis under laser irradiation due to the formation of NCs that have extended accumulation within the arthritis region and limited intravasation back to the blood circulation. The designed light‐addressable Fe3O4‐PEG‐(DA)‐FA NPs may be used as a promising platform for dynamic and precision T1/T2‐weighted MR imaging of other diseases.
Development of cost-effective and highly efficient nanoprobes for targeted tumor single-photon emission computed tomography (SPECT)/computed tomography (CT) dual-mode imaging remains a challenging task. Here, multifunctional dendrimer-entrapped gold nanoparticles (Au DENPs) modified with folic acid (FA) and labeled with (99m)Tc were synthesized for targeted dual-mode SPECT/CT imaging of tumors. Generation 2 (G2) poly(amidoamine) (PAMAM) dendrimers (G2-NH2) conjugated with cyclic diethylenetriamine pentaacetic anhydride (cDTPAA) via an amide linkage and FA via a spacer of polyethylene glycol (PEG) were used for templated synthesis of Au core NPs, followed by labeling of (99m)Tc via chelation. The thus created multifunctional Au DENPs were well-characterized. It is shown that particles with an average Au core diameter of 1.6 nm can be dispersed in water, display stability under different conditions, and are cytocompatible in the studied concentration range. Further results demonstrate that the multifunctional nanoprobe is able to be utilized for targeted SPECT/CT dual-mode imaging of cancer cells having FA receptor (FAR)-overexpression in vitro and the established subcutaneous tumor model in vivo within a time frame up to 4 h. The formed multifunctional Au DENPs synthesized using dendrimers of low-generation may be employed as an effective and economic nanoprobe for SPECT/CT imaging of different types of FAR-expressing tumors.
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