Reperfusion injury is still a major challenge that impedes neuronal survival in ischemic stroke. However, the current clinical treatments are remained on single pathological process, which are due to lack of comprehensive neuroprotective effects. Herein, a macrophage‐disguised honeycomb manganese dioxide (MnO
2
) nanosphere loaded with fingolimod (FTY) is developed to salvage the ischemic penumbra. In particular, the biomimetic nanoparticles can accumulate actively in the damaged brain via macrophage‐membrane protein‐mediated recognition with cell adhesion molecules that are overexpressed on the damaged vascular endothelium. MnO
2
nanosphere can consume excess hydrogen peroxide (H
2
O
2
) and convert it into desiderated oxygen (O
2
), and can be decomposed in acidic lysosome for cargo release, so as to reduce oxidative stress and promote the transition of M1 microglia to M2 type, eventually reversing the proinflammatory microenvironment and reinforcing the survival of damaged neuron. This biomimetic nanomedicine raises new strategy for multitargeted combined treatment of ischemic stroke.
Metabolic interactions between different
cell types in the tumor
microenvironment (TME) often result in reprogramming of the metabolism
to be totally different from their normal physiological processes
in order to support tumor growth. Many studies have attempted to inhibit
tumor growth and activate tumor immunity by regulating the metabolism
of tumors and other cells in TME. However, metabolic inhibitors often
suffer from the heterogeneity of tumors, since the favorable metabolic
regulation of malignant cells and other cells in TME is often inconsistent
with each other. Therefore, we reported the design of a pH-sensitive
drug delivery system that targets different cells in TME successively.
Outer membrane vesicles (OMVs) derived from Gram-negative bacteria
were applied to coload paclitaxel (PTX) and regulated in development
and DNA damage response 1 (Redd1)-siRNA and regulate tumor metabolism
microenvironment and suppress tumor growth. Our siRNA@M-/PTX-CA-OMVs
could first release PTX triggered by the tumor pH (pH 6.8). Then the
rest of it would be taken in by M2 macrophages to increase their level
of glycolysis. Great potential was observed in TAM repolarization,
tumor suppression, tumor immune activation, and TME remolding in the
triple-negative breast cancer model. The application of the OMV provided
an insight for establishing a codelivery platform for chemical drugs
and genetic medicines.
A versatile tumor-targeting stimuli-responsive theranostic platform for peritoneal metastases of colorectal cancer is proposed in this work for tumor tracking and photothermal-enhanced chemotherapy. A quenched photosensitizer ("off" state) is developed and escorted into a tumor-targeting oxaliplatin-embedded micelle. Once reaching the tumor cell, the micelle is clasped to release free oxaliplatin, as well as the "off" photosensitizer, which is further activated ("turned-on") in the tumor reducing microenvironment to provide optical imaging and photothermal effect. The combined results from hyperthermia-enhanced chemotherapy, deep penetration, perfused O 2 , and the leveraged GSH-ROS imbalance in tumor cells are achieved for improved antitumor efficacy and reduced systematic toxicity.
The rapid postoperative recurrence and short survival time of glioblastoma (GBM) patients necessitate immediate and effective postoperative treatment. Herein, an immediate and mild postoperative local treatment strategy is developed that regulates the postoperative microenvironment and delays GBM recurrence. Briefly, an injectable hydrogel system (imGEL) loaded with Zn(II)2‐AMD3100 (AMD‐Zn) and CpG oligonucleotide nanoparticles (CpG NPs) is injected into the operation cavity, with long‐term function to block the recruitment of microglia/ macrophages and activate cytotoxic T cells. The finding indicated that the imGEL can regulate the immune microenvironment, inhibit GBM recurrence, and gain valuable time for subsequent adjuvant clinical chemotherapy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.