Light-Induced ROS Generation and 2-DG-Activated Endoplasmic Reticulum Stress by Antitumor Nanosystems: An Effective Combination Therapy by Regulating the Tumor Microenvironment.

A multimodal cancer therapeutic nanoplatform is reported. It demonstrates a promising approach to synergistically regulating the tumor microenvironment. The combination of intracellular reactive oxygen species (ROS) generated by irradiation of photosensitizer and endoplasmic reticulum (ER) stress induced by 2-deoxy-glucose (2-DG) has a profound effect on necrotic or apoptotic cell death. Especially, targeting metabolic pathway by 2-DG is a promising strategy to promote the effect of photodynamic therapy and chemotherapy. The nanoplatform can readily release its cargoes inside cancer cells and combines the advantages of ROS-sensitive releasing chemotherapeutic drugs, upregulating apoptosis pathways under ER stress, light-induced generation of cytotoxic ROS, achieving tumor accumulation, and in vivo fluorescence imaging capability. This work highlights the importance of considering multiple intracellular stresses as design parameters for nanoscale functional materials in cell biology, immune response, as well as medical treatments of cancer, Alzheimer's disease, etc.

Near-Infrared Fluorescent Nanoprobes for Revealing the Role of Dopamine in Drug Addiction.

Brain imaging techniques enable visualizing the activity of central nervous system without invasive neurosurgery. Dopamine is an important neurotransmitter. Its fluctuation in brain leads to a wide range of diseases and disorders, like drug addiction, depression, and Parkinson's disease. We designed near-infrared fluorescence dopamine-responsive nanoprobes (DRNs) for brain activity imaging during drug abuse and addiction process. On the basis of light-induced electron transfer between DRNs and dopamine and molecular wire effect of the DRNs, we can track the dynamical change of the neurotransmitter level in the physiological environment and the releasing of the neurotransmitter in living dopaminergic neurons in response to nicotine stimulation. The functional near-infrared fluorescence imaging can dynamically track the dopamine level in the mice midbrain under normal or drug-activated condition and evaluate the long-term effect of addictive substances to the brain. This strategy has the potential for studying neural activity under physiological condition.

Conjugated polymer nanomaterials for theranostics.

Conjugated polymer nanomaterials (CPNs), as optically and electronically active materials, hold promise for biomedical imaging and drug delivery applications. This review highlights the recent advances in the utilization of CPNs in theranostics. Specifically, CPN-based in vivo imaging techniques, including near-infrared (NIR) imaging, two-photon (TP) imaging, photoacoustic (PA) imaging, and multimodal (MM) imaging, are introduced. Then, CPN-based photodynamic therapy (PDT) and photothermal therapy (PTT) are surveyed. A variety of stimuli-responsive CPN systems for drug delivery are also summarized, and the promising trends and translational challenges are discussed.

Anaerobe-Inspired Anticancer Nanovesicles.

Anaerobic bacteria, such as Clostridium and Salmonella, can selectively invade and colonize in tumor hypoxic regions (THRs) and deliver therapeutic products to destroy cancer cells. Herein, we present an anaerobe nanovesicle mimic that can not only be activated in THRs but also induce hypoxia in tumors by themselves. Moreover, inspired by the oxygen metabolism of anaerobes, we construct a light-induced hypoxia-responsive modality to promote dissociation of vehicles and activation of bioreductive prodrugs simultaneously. In vitro and in vivo experiments indicate that this anaerobe-inspired nanovesicle can efficiently induce apoptotic cell death and significantly inhibit tumor growth. Our work provides a new strategy for engineering stimuli-responsive drug delivery systems in a bioinspired and synergistic fashion.

ATP-Responsive and Near-Infrared-Emissive Nanocarriers for Anticancer Drug Delivery and Real-Time Imaging.

Stimuli-responsive and imaging-guided drug delivery systems hold vast promise for enhancement of therapeutic efficacy. Here we report an adenosine-5'-triphosphate (ATP)-responsive and near-infrared (NIR)-emissive conjugated polymer-based nanocarrier for the controlled release of anticancer drugs and real-time imaging. We demonstrate that the conjugated polymeric nanocarriers functionalized with phenylboronic acid tags on surface as binding sites for ATP could be converted to the water-soluble conjugated polyelectrolytes in an ATP-rich environment, which promotes the disassembly of the drug carrier and subsequent release of the cargo. In vivo studies validate that this formulation exhibits promising capability for inhibition of tumor growth. We also evaluate the metabolism process by monitoring the fluorescence signal of the conjugated polymer through the in vivo NIR imaging.

Light-Activated Hypoxia-Responsive Nanocarriers for Enhanced Anticancer Therapy.

A light-activated hypoxia-responsive conjugated polymer-based nanocarrier is developed for efficiently producing singlet oxygen ((1) O2 ) and inducing hypoxia to promote release of its cargoes in tumor cells, leading to enhanced antitumor efficacy. This dual-responsive nanocarrier provides an innovative design guideline for enhancing traditional photodynamic therapeutic efficacy integrated with a controlled drug-release modality.