Multifunctional and Redox-Responsive Self-Assembled Magnetic Nanovectors for Protein Delivery and Dual-Modal Imaging

Nanoparticle (NP) based model carriers present an emerging strategy for protein delivery. However, constructing a multifunctional nanocarrier with high loading capacity, diagnostic imaging capacity, and controlled release capability is a tremendous challenge for protein delivery systems. Thus, we herein report on the fabrication of redox-responsive magnetic nanovectors (termed RMNs) through self- assembly of Fe₃O₄ NPs and redox-responsive polymer ligands, which could effectively transport protein and trigger intracellular protein release. These RMNs also exhibited low toxicity, high stability, biocompatibility, and <i>T</i>₂-weighted contrast-enhancement properties. In addition, they presented a quantized positively charged surface that had the capacity to load cyanine 5.5 (Cy5.5) labeled human serum albumin (HSA) with high loading efficiency (∼84%) via electrostatic interactions and which favored cellular uptake. Notably, studies of the in vitro protein release showed that HSA-Cy5.5-loaded RMNs (RMNs-HSA-Cy5.5) presented minimal cumulative release behavior under physiological conditions but release was rapidly enhanced under high glutathione concentration conditions. Confocal microscopy further revealed that protein was delivered and localized at the perinuclear region of tumor cells. Moreover, the in vivo imaging results confirmed that RMNs-HSA-Cy5.5 could serve as a dual-modal probe for simultaneous near-infrared fluorescence (NIRF) imaging and magnetic resonance (MR) imaging, which can be used for breast cancer diagnosis, and verified higher tumor accumulation of transported protein in a living body. Overall, we believe that these multifunctional RMNs exhibit great promise for protein delivery, cancer diagnosis and therapy, and multimodal imaging, as well as clinical applications

One-Step Preparation of pH-Responsive Polymeric Nanogels as Intelligent Drug Delivery Systems for Tumor Therapy

In this work, pH-responsive polypeptide-based nanogels are reported as potential drug delivery systems. By the formation of pH-sensitive benzoic imine bonds, pH-responsive nanogels are constructed using hydrophilic methoxy poly­(ethylene glycol)-<i>b</i>-poly­[<i>N</i>-[<i>N</i>-(2-aminoethyl)-2-aminoethyl]-l-glutamate] (MPEG-<i>b</i>-PNLG) and hydrophobic terephthalaldehyde (TPA) as a cross-linker. At pH 7.4, MPEG-<i>b</i>-PNLG nanogels exhibit high stabilities with hydrophobic inner cores, which allow encapsulation of hydrophobic therapeutic agents. Under tumoral acidic environments (pH ∼6.4), the cleavage of benzoic imine bonds induces the destruction of MPEG-<i>b</i>-PNLG nanogels and leads to rapid release of their payloads. The formation and pH sensitivity of the nanogels are investigated by dynamic light scattering. These nanogels exhibit excellent stabilities in the presence of salt or against dilution. The globular morphologies of the nanogels are confirmed using transmission electron microscopy. Doxorubicin is used as a model drug to evaluate drug encapsulation and release. Finally, the anticancer activities of the drug-encapsulated nanogels are assessed in vitro

Multifunctional Polymer Ligand Interface CdZnSeS/ZnS Quantum Dot/Cy3-Labeled Protein Pairs as Sensitive FRET Sensors

High-quality CdZnSeS/ZnS alloyed core/thick-shell quantum dots (QDs) as energy donors were first exploited in Förster resonance energy transfer (FRET) applications. A highly efficient ligand-exchange method was used to prepare low toxicity, high quantum yield, stabile, and biocompatible CdZnSeS/ZnS QDs densely capped with multifunctional polymer ligands containing dihydrolipoic acid (DHLA). The resulting QDs can be applied to construct QDs-based Förster resonance energy transfer (FRET) systems by their high affinity interaction with dye cyanine 3 (Cy3)-labeled human serum albumin (HSA). This QD-based FRET protein complex can serve as a sensitive sensor for probing the interaction of clofazimine with proteins using fluorescence spectroscopic techniques. The ability of FRET imaging both in vitro and in vivo not only reveals that the current FRET system can remain intact for 2 h but also confirms the potential of the FRET system to act as a nanocarrier for intracellular protein delivery or to serve as an imaging probe for cancer diagnosis