No abstract

Macrophages have a leading position in the tumor microenvironment (TME) which paves the way to carcinogenesis. Initially, monocytes and macrophages are recruited to the sites where the tumor develops. Under the guidance of different microenvironmental signals, macrophages would polarize into two functional phenotypes, named as classically activated macrophages (M1) and alternatively activated macrophages (M2). Contrary to the anti-tumor effect of M1, M2 exerts anti-inflammatory and tumorigenic characters. In progressive tumor, M2 tumor-associated macrophages (TAMs) are in the majority, being vital regulators reacting upon TME. This review elaborates on the role of TAMs in tumor progression. Furthermore, prospective macrophage-focused therapeutic strategies, including drugs not only in clinical trials but also at primary research stages, are summarized followed by a discussion about their clinical application values. Nanoparticulate systems with efficient drug delivery and improved antitumor effect are also summed up in this article.

No abstract

Glucose‐oxidase (GOx)‐mediated starvation by consuming intracellular glucose has aroused extensive exploration as an advanced approach for tumor treatment. However, this reaction of catalytic oxidation by GOx is highly dependent on the on‐site oxygen content, and thus starvation therapy often suffers unexpected anticancer outcomes due to the intrinsic tumorous hypoxia. Herein, porous platinum nanospheres (pPts), incorporated with GOx molecules (PtGs), are synthesized to enable synergistic cancer therapy. In this system, GOx can effectively catalyze the oxidation of glucose to generate H2O2, while pPt triggers the decomposition of both endogenous and exogenous H2O2 to produce considerable content of O2 to facilitate the glucose consumption by GOx. Meanwhile, pPt induces remarkable content of intracellular reactive oxygen species (ROS) under an alternating electric field, leading to cellular oxidative stress injury and promotes apoptosis following the mechanism of electrodynamic therapy (EDT). In consequence, the PtG nanocomposite exhibits significant anticancer effect both in vitro and in vivo. This study has therefore demonstrated a fascinating therapeutic platform enabling oxygen‐inductive starvation/EDT synergistic strategy for effective tumor treatment.

Perineural invasion (PNI) is an ominous event strongly linked to poor clinical outcome. Cells residing within peripheral nerves collaborate with cancer cells to enable PNI but the contributing conditions within the tumor microenvironment are not well understood. Here we show that CCR2-expressing inflammatory monocytes (IM) are preferentially recruited to sites of PNI, where they differentiate into macrophages and potentiate nerve invasion through a cathepsin B-mediated process. A series of adoptive transfer experiments with genetically engineered donors and recipients demonstrated that IM recruitment to nerves was driven by CCL2 released from Schwann cells at the site of PNI, but not CCL7, an alternate ligand for CCR2. Interruption of either CCL2-CCR2 signaling or cathepsin B function significantly impaired PNI in vivo. Correlative studies in human specimens demonstrated that cathepsin B producing macrophages were enriched in invaded nerves, which was associated with increased local tumor recurrence. These findings deepen our understanding of PNI pathogenesis and illuminate how PNI is driven in part by corruption of a nerve repair program. Further, they support the exploration of inhibiting IM recruitment and function as a targeted therapy for PNI.

No abstract

No abstract

To date, only few a types of nanomedicines have been made available for clinical use even in the most common liposomal delivery systems, due to significant constraints, including poor targeting of specific cells, hindered penetration, and accelerated clearance. Various intricate designs have been generated and show improvements, while also bringing new problems. Biological cells, possessing advantages like low immunogenicity, long circulation time, receptors integration, and innate targeting capability. Herein, liposomes are innovatively functionalized with a stem cell membrane through a facile approach. The biomimetic vesicles achieve controlled release, exhibit better stability, longer circulation time, and targeted delivery. Loading with curcumin leads to enhanced survival rate of ischemic stroke mice with a single injection (from ≈30% to over 90%). The versatility of the method is verified by differently charged liposomes modification and erythrocyte membrane derived vesicles preparation. Overall, the cell membrane derived biomimetic vesicles achieve targeted delivery and versatility prepared by a facile approach, as well as effortless preparation.