No abstract

Golden vaccine for cancers. Gold nanoparticles enable efficient antigen delivery to dendritic cells and then activate the cells to facilitate cross-presentation, inducing antigen-specific cytotoxic T-lymphocyte responses for effective cancer therapy.

Standardized poly(ethylene glycol)-modified (PEGylated) liposomes, which have been widely used in research as well as in pre-clinical and clinical studies, are typically constructed using PEG with a molecular weight of 2000 Da (PEG2000). Targeting ligands are also generally conjugated using various functionalized PEG2000. However, although standardized protocols have routinely used PEG2000, it is not because this molecular weight PEG has been optimized to enhance tumor uptake of nanoparticles. Herein, we investigated the effect of various PEG lipid pairings—that is, PEG lipids for targeting-ligand conjugation and PEG lipids for achieving 'stealth' function—on in vitro cancer cell- and in vivo tumor-targeting efficacy. A class of high-affinity peptides (aptides) specific to extra domain B of fibronectin (APTEDB) was used as a representative model for a cancer-targeting ligand. We synthesized a set of aptide-conjugated PEGylated phospholipids (APTEDB‑PEG2000‑DSPE and APTEDB‑PEG1000‑DSPE) and then paired them with methoxy-capped PEGylated phospholipids with diverse molecular weights (PEG2000, PEG1000, PEG550, and PEG350) to construct various aptide-conjugated PEGylated liposomes. The liposomes with APTEDB‑PEG2000/PEG1000 and APTEDB‑PEG1000/PEG550 pairings had the highest uptake in EDB-positive cancer cells. Furthermore, in a U87MG xenograft model, APTEDB‑PEG2000/PEG1000 liposomes retarded tumor growth to the greatest extent, followed closely by APTEDB‑PEG1000/PEG550 liposomes. Among the PEGylated liposomes tested, pairs in which the methoxy-capped PEG length was about half that of the targeting ligand-displaying PEG exhibited the best performance, suggesting that PEG pairing is a key consideration in the design of drug-delivery vehicles.

Ferrocene-containing nanoparticles show reversible redox activity that could trigger drug release mediated by reactive oxygen species (ROS).

STAT3 promotes the survival, proliferation, metastasis, immune escape, and drug resistance of cancer cells, making its targeting an appealing prospect. However, although multiple inhibitors of STAT3 and its regulatory or effector pathway elements have been developed, bioactive agents have been somewhat elusive. In this report, we report the identification of a specific STAT3-binding peptide (APT STAT3 ) through phage display of a novel "aptide" library. APT STAT3 bound STAT3 with high specificity and affinity ($231 nmol/L). Addition of a cell-penetrating motif to the peptide to yield APT STAT3 -9R enabled uptake by murine B16F1 melanoma cells. Treatment of various types of cancer cells with APT STAT3 -9R blocked STAT3 phosphorylation and reduced expression of STAT targets, including cyclin D1, Bcl-xL, and survivin. As a result, APT STAT3 -9R suppressed the viability and proliferation of cancer cells. Furthermore, intratumoral injection of APT STAT3 -9R exerted potent antitumor activity in both xenograft and allograft tumor models. Our results offer a preclinical proof-of-concept for APT STAT3 as a tractable agent for translation to target the broad array of cancers harboring constitutively activated STAT3. Cancer Res; 74(8);