One-Pot Synthesis of Redox-Labile Polymer Capsules via Emulsion Droplet-Mediated Precipitation Polymerization

Monodisperse poly­(vinylcaprolactam) (PVCL)-based capsules are prepared by precipitation polymerization of vinylcaprolactam (VCL) onto dimethyldiethoxysilane (DMDES) emulsion droplets and removal of the DMDES templates by ethanol. Polymer chains in the shells can be cross-linked during the polymerization by disulfide-containing cross-linker <i>N</i>,<i>N</i>′-bis­(acryloyl) cystamine, which endows the capsules with an excellent redox-labile property. Versatility of this technique to prepare capsules with diverse components is demonstrated by the copolymerization of methacrylic acid (MAA) and VCL in the shell to prepare poly­(vinylcaprolactam-<i>co</i>-methacrylic acid) (P­(VCL-<i>co</i>-MAA)) capsules. The disulfide-bonded capsules can degrade efficiently into low molecular weight species (ca. 1200 Da) when the capsules are incubated with 10 mM glutathione (GSH) as the reducing agent. Delivery of the anticancer drug (doxorubicin, DOX) was also investigated in the P­(VCL-<i>co</i>-MAA) capsules. The cumulative <i>in vitro</i> release of DOX-loaded capsules allows a relatively low DOX release at pH 7.4. However, a burst release (ca. 90% in 6 h) of DOX was observed in the presence of 10 mM GSH. Cell viability assays show that the P­(VCL-<i>co</i>-MAA) capsules have negligible cytotoxicity to HeLa cancer cells. In comparison, DOX-loaded P­(VCL-<i>co</i>-MAA) capsules cause significant cell death following internalization. The reported capsules represent a novel and versatile class of stimuli-responsive carriers for controlled drug delivery

A Generic Magnetic Microsphere Platform with “Clickable” Ligands for Purification and Immobilization of Targeted Proteins

While much effort has been made to prepare magnetic microspheres (MMs) with surface moieties that bind to affinity tags or fusion partners of interest in the recombinant proteins, it remains a challenge to develop a generic platform that is capable of incorporating a variety of capture ligands by a simple chemistry. Herein, we developed core–shell structured magnetic microspheres with a high magnetic susceptibility and a low nonspecific protein adsorption. Surface functionalization of these MMs with azide groups facilitates covalent attachment of alkynylated ligands on their surfaces by “click” chemistry and creates a versatile platform for selective purification and immobilization of recombinant proteins carrying corresponding affinity tags. The general applicability of the approach was demonstrated in incorporating four widely used affinity ligands with different reactive groups (−CHO, −SH, −COOH, and −NH₂) onto the MMs platform for purification and immobilization of targeted proteins. The azide-functionalized MMs would be applicable for a variety of ligands and substrates that are amenable to alkynylation modification

Polydopamine-Coated Magnetic Composite Particles with an Enhanced Photothermal Effect

Recently, photothermal therapy (PTT) that utilizes photothermal conversion (PTC) agents to ablate cancer under near-infrared (NIR) irradiation has attracted a growing amount of attention because of its excellent therapeutic efficacy and improved target selectivity. Therefore, exploring novel PTC agents with an outstanding photothermal effect is a current research focus. Herein, we reported a polydopamine-coated magnetic composite particle with an enhanced PTC effect, which was synthesized simply through coating polydopamine (PDA) on the surface of magnetic Fe₃O₄ particles. Compared with magnetic Fe₃O₄ particles and PDA nanospheres, the core–shell nanomaterials exhibited an increased NIR absorption, and thus, an enhanced photothermal effect was obtained. We demonstrated the <i>in vitro</i> and <i>in vivo</i> effects of the photothermal therapy using our composite particles and their ability as a contrast agent in the <i>T</i>₂-weighted magnetic resonance imaging. These results indicated that the multifunctional composite particles with enhanced photothermal effect are superior to magnetic Fe₃O₄ particles and PDA nanospheres alone

Plant Protein-Directed Synthesis of Luminescent Gold Nanocluster Hybrids for Tumor Imaging

Nowadays, fluorescence detection has emerged as one of the most frequently used noninvasive biosensing methods to selectively monitor biological processes within living systems. Among fluorescent nanoparticles (NPs), gold nanoclusters (AuNCs) have been intensively studied because of their intrinsic fluorescence and their endowed biocompatible surface. Herein, we selected an abundant, low-cost, and sustainable plant protein, the pea protein isolate (PPI), for its excellent biocompatibility, biodegradability, and nonallergenic character to be employed as both a reducing and stabilizing agent to facilely produce AuNCs exhibiting a strong red fluorescence. Afterward, the formed AuNCs/PPI mixture was able to self-assemble into NPs (AuNCs/PPI NPs) with the size of about 100 nm simply through a dialyzing process. Taking advantage from the protein nature of PPI, AuNCs/PPI NPs demonstrate both excellent biocompatibility and colloidal stability. Moreover, AuNCs/PPI NPs showed a great capability when employed as a bioimaging probe for both in vitro and in vivo imaging. Finally, AuNCs/PPI NPs were coated with red blood cell (RBC) membranes to improve their blood circulation property and enhance their tumor enrichment ability to meet the requirement for practical use. Results convincingly show that such super NPs (RBC-coated AuNCs/PPI NPs) were able to successfully locate tumor in vivowith an excellent imaging capability, which provides a new strategy for bioimaging with fluorescent NPs

Blocking Autophagic Flux Enhances Iron Oxide Nanoparticle Photothermal Therapeutic Efficiency in Cancer Treatment

Autophagy is a conservative eukaryotic pathway which plays a crucial role in maintaining cellular homeostasis, and dysfunction of autophagy is usually associated with pathological conditions. Recently, emerging reports have stressed that various types of nanomaterials and therapeutic approaches interfere with cellular autophagy process, which has brought up concerns to their future biomedical applications. Here, we present a study elaborating the relationships between autophagy and iron oxide nanoparticle (IONP)-mediated photothermal therapy in cancer treatment. Our results reveal that IONP photothermal effect could lead to autophagy induction in cancerous MCF-7 cells in a laser dose-dependent manner, and the inhibition of autophagy would enhance the photothermal cell killing by increasing cell apoptosis. In an MCF-7 xenograft model, cotreatment of autophagy inhibitor and IONP under laser exposure could promote the tumor inhibition rate from 43.26 to 68.56%, and the tumor immunohistochemistry assay of microtubule-associated protein 1-light chain 3 (LC3) and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling also demonstrate augmentation in both autophagosomes accumulation and apoptosis in vivo. This work helps us to better understand the regulation of autophagy during IONP-mediated photothermal therapy and provides us with a potential combination therapeutic approach of autophagy modulators and photothermal agents

Fluorescent Carbonaceous Nanodots for Noninvasive Glioma Imaging after Angiopep‑2 Decoration

Fluorescent carbonaceous nanodots (CDs) have attracted much attention due to their unique properties. However, their application in noninvasive imaging of diseased tissues was restricted by the short excitation/emission wavelengths and the low diseased tissue accumulation efficiency. In this study, CDs were prepared from glucose and glutamic acid with a particle size of 4 nm. Obvious emission could be observed at 600 to 700 nm when CDs were excited at around 500 nm. This property enabled CDs with capacity for deep tissue imaging with low background adsorption. Angiopep-2, a ligand which could target glioma cells, was anchored onto CDs after PEGylation. The product, An-PEG-CDs, could target C6 glioma cells with higher intensity than PEGylated CDs (PEG-CDs), and endosomes were involved in the uptake process. In vivo, An-PEG-CDs could accumulate in the glioma site at higher intensity, as the glioma/normal brain ratio for An-PEG-CDs was 1.73. The targeting effect of An-PEG-CDs was further demonstrated by receptor staining, which showed An-PEG-CDs colocalized well with the receptors expressed in glioma. In conclusion, An-PEG-CDs could be successfully used for noninvasive glioma imaging

New Application of Old Material: Chinese Traditional Ink for Photothermal Therapy of Metastatic Lymph Nodes

Finding a simple and effective strategy to eliminate tumor metastatic lymph nodes is highly desired in clinical tumor treatment. Herein, we reported a Chinese traditional ink (Hu-ink)-based treatment for photothermal therapy (PTT) of tumor metastatic lymph nodes. By simple dilution, stable Chinese traditional ink dispersion was obtained, which presents excellent photothermal effect because of its high absorption in near-infrared (NIR) region. Meanwhile, as revealed by staining and photoacoustic imaging, Hu-ink could transfer to nearby lymph nodes after directly injected into the primary tumors. Under the guidance of dual-modality mapping, the metastatic sentinel lymph nodes could be subsequently eliminated by NIR irradiation. The good biocompatibility of Hu-ink has also been verified by a series of experiments. Therefore, the Hu-ink-based treatment exhibits great potential for PTT of tumor metastatic lymph nodes in future clinical practice