A light‐activated hypoxia‐responsive conjugated polymer‐based nanocarrier is developed for efficiently producing singlet oxygen (1O2) 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.
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.
A biomimetic vesicle mimics the natural mode of tumor targeting and therapeutic drug delivery of anaerobic bacteria. The nanovesicle is stable in cells with normal physiological redox and oxygen balance; however, once disrupted by external light stimuli, it shows dual synergistic anticancer actions with enhanced therapeutic efficacy.
In recent years, neurodegenerative diseases, such as Parkinson’s or Alzheimer’s diseases, are rapidly rising in prevalence. The main hallmark of Parkinson’s disease is the falling levels of ...neurotransmitter dopamine in the mid-brain with dopaminergic neurons losing. Typical therapeutic solutions, including drugs, deep brain stimulation, and cell transplantation, can only alleviate the symptoms of Parkinson’s disease. It is a tremendous challenge to reverse the function degeneration of the crucial dopaminergic neurons. Herein, we develop a core-satellite-like nanoassembly (PDA-AFn (by integrating polydopamine nanoparticles and apoferritin)) to raise the expression of tyrosine hydroxylase (TH), a rate-limiting enzyme in the formation of the dopamine. Both components in the nanoassembly could cooperate with each other, not only elaborately regulate the iron homeostasis and redox microenvironment, but also utilize excessive reactive oxygen species (ROS) and iron ions in the damaged neurons to supply extra dopamine and enhance TH activity, and consequently restore the function of the degenerated neurons. Remarkably, the nanoassembly-treatment relieves the dyskinesia and dramatical increases the tyrosine hydroxylase and dopamine level in the midbrain of Parkinson’s disease model mice. It is an explicit yet inspiring advance in treatment of the neurodegeneration.
Acne vulgaris is a common inflammatory skin disease associated with a colonization of Propionibacterium acnes (P. acnes), which can cause both physiological and psychological impact to the patients. ...Although antibiotic cream is commonly used to treat acne, limited transport of drug to the lesions within the pilosebaceous unit leads to poor bactericidal effect. Here, the authors described a new method of drug administration using a reactive oxygen species (ROS)‐responsive microneedle (MN) patch for anti‐acne therapy. Compared to the commonly used anti‐acne cream, enhanced efficacy toward dermis lesions can be achieved through the skin penetration by MNs. A controlled and sustained drug release in response to the over‐generated ROS within acne is also important for improving the antibacterial effect and reducing the side effects. In addition, the patch base, formed by hyaluronic acid (HA) and diatomaceous earth (DE) with high physical adsorption capability, is beneficial for accelerating healing of skin via the absorption of pus and dead cell debris. In vivo studies in a P. acnes‐induced mouse model demonstrated this bioresponsive patch with adsorption capability could efficiently reduce the skin swelling and inhibit the bacterial growth.
A reactive oxygen species (ROS)‐responsive microneedle platform is developed for effective transdermal drug delivery to treat acne. Microneedles penetration through stratum corneum facilitates direct interaction between antimicrobial therapeutics and bacteria in the pilosebaceous unit. In addition, the ROS‐triggered drug release enables sustained drug concentrations in therapeutic levels around the acne area. This bioresponsive patch demonstrates a significantly enhanced bactericidal effect compared to traditional anti‐acne cream.
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.
Biomimetische Vesikel imitieren den natürlichen Mechanismus der Tumorerkennung und des Wirkstofftransports anaerober Bakterien. Die Nanovesikel sind in Zellen mit einer normalen physiologischen Redox‐ und Sauerstoffbilanz stabil. Bei Lichteinstrahlung brechen sie auf und entfalten ihre duale synergistische Antikrebswirkung mit erhöhter therapeutischer Wirksamkeit.
Chemotherapy is one of the main treatments for oral squamous cell carcinoma (OSCC), especially as a combined modality approach with and after surgery or radiotherapy. Limited therapeutic efficiency ...and serious side effects greatly restrict the clinical performance of chemotherapeutic drugs. The development of smart nanomedicines has provided new research directions, to some extent. However, the involvement of complex carrier compositions inevitably brings biosafety concerns and greatly limits the “bench-to-bed” translation of most nanomedicines reported. In this study, a carrier-free self-assembled prodrug was fabricated by two triterpenes (glycyrrhetinic acid, GA and ginsenoside Rh2, Rh2) isolated from medicinal plants, licorice, and ginseng, for the targeted and highly effective treatment of OSCC. Reactive oxygen species (ROS) self-supplied molecule TK-GA2 was synthesized with ROS-responsive thioketal linker and prodrug was prepared by a rapid-solvent-exchange method with TK-GA2 and Rh2. After administration, oral tumor cells transported large amounts of prodrugs with glucose ligands competitively. Endogenous ROS in oral tumor cells then promoted the release of GA and Rh2. GA further evoked the generation of a large number of ROS to help self-boosted drug release and increase oxidative stress, synergistically causing tumor cell apoptosis with Rh2. Overall, this carrier-free triterpene-based prodrug might provide a preeminent opinion on the design of effective chemotherapeutics with low systemic toxicity against OSCC.
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.
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.
An anaerobe‐inspired drug delivery vehicle is described by Q. D. Shen, Z. Gu, and co‐workers in their Communication on page 2588 ff. The biomimetic nanovesicles are stable in cells with normal ...physiological redox and oxygen balance. Upon disruption by external light stimuli, they show dual synergistic anticancer actions with enhanced therapeutic efficacy.
A light‐activated hypoxia‐responsive drug‐delivery vehicle is described by Q.‐D. Shen, Z. Gu, and co‐workers on page 3313. This conjugated‐polymer‐based nanocarrier can be activated by ...photoirradiation, producing singlet oxygen (1O2) and inducing hypoxia to promote release of its cargo inside tumor cells for enhanced anticancer efficacy.
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