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The design and fabrication of nanoplatforms with both nuclear medical imaging and therapeutic functions remain challenging in current precision nanomedicine. Herein, we report the design of a novel nanoplatform based on glucose-modified dendrimer-entrapped gold nanoparticles (Au DENPs) labeled with radionuclide 68Ga and incorporated with cytosine-guanine (CpG) oligonucleotide for positron emission tomography (PET)/computed tomography (CT) dual-mode imaging and immunotherapy of tumors. In this study, generation 5 poly(amidoamine) (PAMAM) dendrimers were first modified to have 8.2 DOTA and 7.3 polyethylene glycol with the other end functionalized with 2-amino-2-deoxy- D -glucose (DG) for each dendrimer, entrapped with Au NPs, and then radiolabeled with 68Ga through the DOTA chelation. The synthesized DG-Au DENPs have good cytocompatibility, targeting specificity toward cancer cells expressing glucose transporters, and the ability to be labeled by 68Ga with great labeling efficiency (≥85%) and stability (≥95%). After being loaded with CpG, the formed DG-Au DENPs/CpG polyplexes were proven to be used for tumor dual-mode PET/CT imaging and immunotherapy by effectively maturing dendritic cells to initiate a T cell-based antitumor immune response in vivo. Compared with the DG-free polyplexes, the developed DG-Au DENPs/CpG polyplexes show a much more sensitive imaging effect and better inhibition effect of tumors. These findings demonstrate a unique design of 68Ga-labeled DG-Au DENPs, a promising theranostic nanoplatform that may be extended to tackle different tumor types. [ABSTRACT FROM AUTHOR]

Development of carrier‐free full‐active nanoplatforms to exert efficient tumor therapeutics and prevent tumor recurrence remains to be a challenging task. Herein, a microfluidic synthesis of self‐assembled carrier‐free gossypol (Gos)‐iron ion (Fe3+)‐toyocamycin (Toy) nanocapsules (GFT NCs) is developed for tumor magnetic resonance (MR) imaging and chemo‐chemodynamic‐immune therapy. The constructed GFT NCs with an average diameter of 101.9 nm display desirable colloidal stability, uniformity, pH‐responsive drug release profile, and enhanced r1 relaxivity (3.71 mm−1s−1) under an acidic condition. The NCs‐mediated co‐delivery of Gos, Fe3+, and Toy induces apparent immunogenic cell death by leveraging a combination of Gos‐induced mitochondrial dysfunction, Fe3+‐mediated chemodynamic therapy, and Toy‐amplified endoplasmic reticulum stress, thus efficiently inhibiting tumor growth and metastasis while triggering a potent antitumor immunity. When combined with programmed cell death ligand 1 antibody, the GFT NCs significantly enhance immune activation and establish tumor‐specific immune memory effects, thereby preventing tumor recurrence. Compared to Magnevist, a commercial T1 MR imaging contrast agent, the GFT NCs offer superior tumor T1‐weighted MR imaging at equivalent Fe or Gd concentrations in vivo. The developed GFT NCs represent a potential carrier‐free full‐active nanomedicine formulation for multifaceted and enhanced immunotherapy across diverse tumor types. [ABSTRACT FROM AUTHOR]

The design and fabrication of nanoplatforms with both nuclear medical imaging and therapeutic functions remain challenging in current precision nanomedicine. Herein, we report the design of a novel nanoplatform based on glucose-modified dendrimer-entrapped gold nanoparticles (Au DENPs) labeled with radionuclide 68 Ga and incorporated with cytosine-guanine (CpG) oligonucleotide for positron emission tomography (PET)/computed tomography (CT) dual-mode imaging and immunotherapy of tumors. In this study, generation 5 poly(amidoamine) (PAMAM) dendrimers were first modified to have 8.2 DOTA and 7.3 polyethylene glycol with the other end functionalized with 2-amino-2-deoxy-D-glucose (DG) for each dendrimer, entrapped with Au NPs, and then radiolabeled with 68 Ga through the DOTA chelation. The synthesized DG-Au DENPs have good cytocompatibility, targeting specificity toward cancer cells expressing glucose transporters, and the ability to be labeled by 68 Ga with great labeling efficiency (≥85%) and stability (≥95%). After being loaded with CpG, the formed DG-Au DENPs/CpG polyplexes were proven to be used for tumor dual-mode PET/CT imaging and immunotherapy by effectively maturing dendritic cells to initiate a T cell-based antitumor immune response in vivo . Compared with the DG-free polyplexes, the developed DG-Au DENPs/CpG polyplexes show a much more sensitive imaging effect and better inhibition effect of tumors. These findings demonstrate a unique design of 68 Ga-labeled DG-Au DENPs, a promising theranostic nanoplatform that may be extended to tackle different tumor types.

Recent advances in the field of nanotechnology bring an alternative approach to personalized medicine in cancer treatment. Nanogels (NGs) are among the nanosized superconstructs composed of amphiphilic or hydrophilic polymer networks. The design of different types of biodegradable polymer-based NGs in various biomedical applications has received extensive attention, due to their unique physicochemical properties such as highly porous structure, stimuli-responsiveness, and mimicking of some biological properties. In this review, we concisely surveyed the synthesis of dendrimer-based NGs synthesized via different methods including covalent conjugation, inverse nanoprecipitation, physical cross-linking, or self-assembly for various cancer nanomedicine applications, particularly for drug delivery, gene delivery, photothermal therapy, and combination therapy, as well as for biological imaging-guided chemotherapy. Additionally, we provide herein future perspective toward the new design of dendrimer-based NGs for different cancer nanomedicine uses.