Sommer Fitzsimmons (northspace40)

MicroRNAs (miRNAs) play crucial roles in maintaining normal physiological processes by regulating gene expression network and thus the tumor-suppressive miRNA has emerged as a promising antitumor agent for cancer treatment. However, targeted delivery of miRNA remains a challenge owing to its intrinsic macromolecular and negatively-charged features. Herein, we first employ the miRNA as crosslinker to construct a nucleic acid nanogel, in which miRNA is embedded and protected inside the three-dimensional (3D) nanostructure. Thereafter, nanobody (Nb) conjugated DNA (Nb-DNA) strands are further loaded on nanogel surface through nucleic acid hybridization, to form a Nb-functionalized nanogel (Nb-nanogel) for tumor-targeted miRNA delivery and antitumor treatment. Both in vitro and in vivo experiments show that nanogel equipped with Nb targeting moieties can greatly promote the miRNA accumulation at the tumor site and cellular uptake efficiency, resulting in significant improvement of the miRNA-mediated antitumor efficacy. This research provides a new approach for targeted miRNA delivery and may pave a new avenue to realize efficient miRNA replacement therapy for cancer treatment.With the prevalence of antibiotic-resistant bacteria, novel antibacterial strategies are urgently needed. In recent years, several antibiotics-independent physical approaches have attracted high attention and interests. Among those approaches, photothermal therapy (PTT), a novel non-invasive therapeutic technique, has exhibited great potentials in dealing with drug-resistant bacteria and bacterial biofilms. Photothermal agents (PTAs), which are either nanomaterials themselves or small molecules loaded in nanoparticles, are the essential element for PTT. How to deliver PTAs in a controlled manner is of great importance for high-efficiency and low-toxicity PTT. Therefore, a comprehensive understanding of various PTAs is required for the better application of PTT in antibacterial treatment. Herein, the physicochemical properties and antibacterial PTT of five types of PTAs are summarized. In addition, the PTT-involved multifunctional theranostics nanoplatforms and the potential approaches for reducing the side effects of PTT (such as targeted delivery and controlled release of PTAs) are also discussed.Development of injectable nanoparticles for delivery of active anticancer compounds often requires complicated schemes that involve tedious synthetic protocols and nanoformulations. In particular, clinical translation of synergistic nanoparticles that can facilitate multimodal therapies remains a considerable challenge. Herein, we describe a self-assembling, small-molecule nanosystem with unique properties, including near-infrared (NIR) light-responsive drug activation, size transformability, combinatorial synergy, and substantially reduced toxicity. Ligation of anticancer cabazitaxel (CTX) drugs via a reactive oxygen species-activatable thioketal linkage generates a dimeric TKdC prodrug, and subsequent coassembly with a photosensitizer, chlorin e6 (Ce6), forms colloidal-stable nanoassemblies (termed psTKdC NAs). Upon NIR laser irradiation, psTKdC NAs are transformed into smaller size particles and facilitate production of pharmacologically active CTX. Importantly, reactive oxygen species yielded by coassembled Ce6 can synergize with chemotherapy to achieve potent combinatorial effects. In a preclinical orthotopic model of an aggressive, human melanoma patient-derived xenograft (PDX), we show that administration of psTKdC NAs followed by laser irradiation produced durable tumor regression, with the tumors being completely eradicated in three of six PDXs. Furthermore, low systemic toxicity of this smart, photo-activatable nanotherapy was observed in animals. The new self-deliverable combinatorial system addresses essential requirements for high efficacy, safety, and translational capacity and deserves further investigation.The main purpose of this study was to eval