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Intelligent nanomedicines integrated with stimuli-responsive components enable on-demand customizable treatment options which would improve therapeutic outcome and reduce systemic toxicity. In this work, we explore the synergistic therapeutic potential of photodynamic therapy and immunometabolic modulation to achieve tumour regression and to trigger an adaptive immunity to prevent tumour recurrence. The therapeutic potential of the fabricated Bioengineered Immunomodulatory Organelle targeted Nanozymes (BIONs) was tested on 3D printed mini-brains which could effectively recapitulate the biologically relevant interactions between glioblastoma cells and macrophages. In the presence of glioblastoma organotypic brain slices, activated BIONs upregulated the cell surface expression of CD86, a costimulatory molecule and CD83, maturation marker, on monocyte derived dendritic cells, suggesting its ability to elicit a strong immune response. Furthermore, the antigen pulsed dendritic cells by chemotaxis and transendothelial migration readily relocate into the draining lymph node where they present the antigenic cargo to enable the proliferation of T lymphocytes. The stealth and tunable catalytic activity of BIONs prevent ROS mediated diseases such as acute kidney injury by providing environment dependent protection without compromising on its promising anti-cancer activity. [Display omitted] [ABSTRACT FROM AUTHOR]

Lung cancer is one of the major causes of cancer-related deaths worldwide. Stimuli-responsive polymers and nanoparticles, which respond to exogenous or endogenous stimuli in the tumor microenvironment, have been widely investigated for spatiotemporal chemotherapeutic drug release applications for cancer chemotherapy. We developed glutathione (GSH)-responsive polyurethane nanoparticles (GPUs) using a GSH-cleavable disulfide bond containing polyurethane that responds to elevated levels of GSH within lung cancer cells. The polyurethane nanoparticles were fabricated using a single emulsion and mixed organic solvent method. Cisplatin-loaded GSH-sensitive nanoparticles (CGPU) displayed a GSH-dose dependent release of cisplatin. In addition, a significant reduction in in vitro survival fraction of A549 lung cancer cells was observed compared to free cisplatin of equivalent concentration (survival fraction of ~0.5 and ~0.7, respectively). The in vivo biodistribution studies showed localization of fluorescently labeled GPUs (~7% of total injected dose per gram tissue) in the lung tumor regions after mouse-tail IV injections in xenograft A549 lung tumor models. The animals exposed to CGPUs also exhibited the inhibition of lung tumor growth compared to animals administered with saline (tumor growth rate of 1.5 vs. 13 in saline) and free cisplatin (tumor growth rate of 5.9) in mouse xenograft A549 lung tumor models within 14 days. These nanoparticles have potential to be used for on-demand drug release for an enhanced chemotherapy to effectively treat lung cancer. Unlabelled Image • Glutathione is abundantly available in lung cancer microenvironment. • Biodegradable polyurethane nanoparticles were fabricated via a single emulsion with a mixed organic solvent. • GSH-sensitive degradable polyurethane nanoparticles (GPUs) released encapsulated cisplatin in response to elevated glutathione levels. • Cisplatin loaded GPUs significantly reduced tumor growth in a subcutaneous A549 lung tumor mouse model compared to the free cisplatin. [ABSTRACT FROM AUTHOR]

The ability to control drug release at a specific physiological target enables the possibility of an enhanced therapeutic effect with reduced off-target toxic side effects. The discipline of controlled drug release has grown to include most areas of medicine with examples in the literature of targeted drug delivery to the majority of organs within the human body. In addition, a variety of external stimuli used to meditate the drug release process have also been investigated. Nonetheless, the concurrent real time monitoring of drug release has not been widely studied. In this manuscript, we present a novel micellar drug delivery system that is not only capable of releasing its cargo when stimulated by light but also provides a real time analysis of the amount of cargo remaining. Controlled drug release from the delivery system was mediated by physicochemical changes of a spiropyran-merocyanine photochromic dyad, while drug quantification was enabled using a Förster Resonance Energy Transfer (FRET) relationship between the photochrome and a co-encapsulated BODIPY fluorophore. The percentage of drug released from the delivery system was significantly greater (24%) when exposed to light irradiation compared to an analogous control maintained in the dark (5%). Furthermore, the fluorescence read-out capability also enabled the drug-release process to be followed in living cells with a significantly reduced fluorescence emission observed for those cells incubated with the delivery system and exposed to light irradiation compared to control cells maintained in the dark. Combined, these results highlight the utility of this approach to theranostic drug delivery with the potential of light-triggered released together with a fluorescence read-out to enable quantification of the drug release process. [ABSTRACT FROM AUTHOR]

Many biomolecules, such as proteins and genes, are presently used as therapeutics. However, their delivery to target sites inside cells is challenging because of their large molecular size, difficulties to pass cellular membranes and their susceptibility for enzymatic and chemical degradation. Nanogels, three-dimensional networks of hydrophilic polymers, are attractive carrier systems for these biotherapeutics because they protect the biologicals against degradation and, importantly, facilitate cell internalization. Furthermore, the development of responsive nanogel delivery systems has resulted in particles that release their payloads due to a certain physiological trigger inside cells, such as in the cytosol or endocytic compartments. This paper reviews and discusses the use of nanogels, with special emphasis on biologically responsive systems, for intracellular delivery of biotherapeutics. [ABSTRACT FROM AUTHOR]

Laser-generated-focused ultrasound (LGFU) holds promise for the high-precision ultrasound therapy owing to its tight focal spot, broad frequency band, and stable excitation with minimal ultrasound-induced heating. We here report the development of the LGFU as a stimulus for promoted drug release from microgels integrated with drug-loaded polymeric nanoparticles. The pulsed waves of ultrasound, generated by a carbon black/polydimethylsiloxane (PDMS)-photoacoustic lens, were introduced to trigger the drug release from alginate microgels encapsulated with drug-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles. We demonstrated the antibacterial capability of this drug delivery system against Escherichia coli by the disk diffusion method, and antitumor efficacy toward the HeLa cell-derived tumor spheroids in vitro . This novel LGFU-responsive drug delivery system provides a simple and remote approach to precisely control the release of therapeutics in a spatiotemporal manner and potentially suppress detrimental effects to the surrounding tissue, such as thermal ablation. [ABSTRACT FROM AUTHOR]

Abstract: Stimuli-sensitive layer-by-layer (LbL) self-assembly systems have generated much interest among researchers worldwide due to the simplicity of the process by which they are produced and their numerous applications in drug delivery. LbL self-assembly systems involve simple alternative adsorption of oppositely charged polyelectrolytes on core materials and are thus considered to be promising tools for drug delivery and biosensing. Here, we discuss the latest findings from research into LbL systems, with special emphasis on drug delivery systems. This review highlights various stimuli-responsive LbL systems and their targeting and biosensory applications. For the convenience of readers, these stimuli-responsive LbL systems are classified as exogenous stimuli-responsive LbL systems and endogenous stimuli-responsive LbL systems. [Copyright &y& Elsevier]