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A surface-engineered cell-derived nanocarrier was developed for efficient cytosolic delivery of encapsulated biologically active molecules inside living cells. Thus, a combination of aromatic-labeled and cationic lipids, instrumental in providing fusogenic properties, was intercalated into the biomimetic shell of self-assembled nanocarriers formed from cell membrane extracts. The nanocarriers were loaded, as a proof of concept, with either bisbenzimide molecules, a fluorescently labeled dextran polymer, the bicyclic heptapeptide phalloidin, fluorescently labeled polystyrene nanoparticles or a ribonucleoprotein complex (Cas9/sgRNA). The demonstrated nanocarrieŕs fusogenic behavior relies on the fusogen-like properties imparted by the intercalated exogenous lipids, which allows for circumventing lysosomal storage, thereby leading to efficient delivery into the cytosolic milieu where cargo regains function., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Translating the potential of thermoplasmonics to cell-derived nanomaterials offers exciting opportunities to fabricate beyond state-of-art artificial biomimetic nanocomposites that upon illumination perform active tasks such as delivery of cargo in complex, dynamic media such as the cytosol of cells. Cell-derived nanoparticles have shown stunning potential to implement cell-specific functions, such as long blood circulation or targeting capabilities, into advanced drug delivery nanosystems. The biomimicry nanotechnology has now advanced to offer new and exciting opportunities to improve the commonly poor in vivo performance of most current nanomedicines, including evading the immune system and targeting specific tissues such as tumors, the latest remaining among the most wanted breakthroughs in nanomedicine. However, the use of cell-derived nanocomposites as stimulus-controlled drug delivery agents remains virtually unexplored. This study reports the fabrication of a plasmonic cell-derived nanocomposite by integrating near-infrared active gold nanorods in its structure. As a proof of concept, the plasmonic nanomembranes are loaded with cell non-permeant antibodies, which upon near-infrared stimulation can be released from the plasmonic nanomembranes into the cytosol of living cells, without impairing cell viability or the antibodies' function. These results set the stage for the development of photoactive cell-derived nanocarriers, which in addition to cell-specific functions promise straightforward access to spatiotemporal-controlled intracellular delivery of antibodies., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

External stimuli such as light, magnetic fields or ultrasounds allow for controlled drug release from nanocarriers with spatiotemporal resolution. Such tetherless approaches may become a straightforward solution to overcome the specificity problems typically associated with nanomedicines. Most of current nanomedicines suffer of very low specificity in vivo, thus rendering efficient targeted delivery among the most wanted breakthroughs in the fields of nanotechnology and medicine. Here we present a sonosensitive, sub-micrometric layer-by-layer capsule system for ultrasound-controlled delivery of macromolecules in vivo. As a proof of concept, the serine protease recombinant tissue plasminogen activator (rtPA), a thrombolytic drug widely employed for the treatment of acute ischemic stroke and other thromboembolic pathologies, is used as encapsulated active compound. The activity of encapsulated rtPA and its ultrasound-induced delivery from the cavity of the capsules are demonstrated. We show, first, that rtPA encapsulation prevents its endogenous biological inactivation and do not interfere with the thrombolytic activity of the drug. Second, upon ultrasound application, delivery of rtPA promotes breakdown of blood clots in vitro. Finally, the ultrasound-triggered in vivo delivery of rtPA from capsules intravenously administrated in mice is demonstrated., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Dynein is a cytoskeletal molecular motor protein that transports cellular cargoes along microtubules. Biomimetic synthetic peptides designed to bind dynein have been shown to acquire dynamic properties such as cell accumulation and active intra- and inter-cellular motion through cell-to-cell contacts and projections to distant cells. On the basis of these properties dynein-binding peptides could be used to functionalize nanoparticles for drug delivery applications., Results: Here, we show that gold nanoparticles modified with dynein-binding delivery sequences become mobile, powered by molecular motor proteins. Modified nanoparticles showed dynamic properties, such as travelling the cytosol, crossing intracellular barriers and shuttling the nuclear membrane. Furthermore, nanoparticles were transported from one cell to another through cell-to-cell contacts and quickly spread to distant cells through cell projections., Conclusions: The capacity of these motor-bound nanoparticles to spread to many cells and increasing cellular retention, thus avoiding losses and allowing lower dosage, could make them candidate carriers for drug delivery.

The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic.

Dual enzymatic reactions were introduced to fabricate programmed gemcitabine (GEM) nanovectors for targeted pancreatic cancer therapy. Dual-enzyme-sensitive GEM nanovectors were prepared by conjugation of matrix metalloproteinase-9 (MMP-9) detachable poly(ethylene glycol) (PEG), cathepsin B-cleavable GEM, and targeting ligand CycloRGD to CdSe/ZnS quantum dots (QDs). The GEM nanovectors decorated with a PEG corona could avoid nonspecific interactions and exhibit prolonged blood circulation time. After GEM nanovectors were accumulated in tumor tissue by the enhanced permeability and retention (EPR) effect, the PEG corona can be removed by overexpressed MMP-9 in tumor tissue and RGD would be exposed, which was capable of facilitating cellular internalization. Once internalized into pancreatic cancer cells, the elevated lysosomal cathepsin B could further promote the release of GEM. By employing dual enzymatic reactions, the GEM nanovectors could achieve prolonged circulation time while maintaining enhanced cellular internalization and effective drug release. The proposed mechanism of the dual enzymatic reaction-assisted GEM delivery system was fully investigated both in vitro and in vivo. Meanwhile, compared to free GEM, the deamination of GEM nanovectors into inactive 2',2'-difluorodeoxyuridine (dFdU) could be greatly suppressed, while the concentration of the activated form of GEM (gemcitabine triphosphate, dFdCTP) was significantly increased in tumor tissue, thus exhibiting superior tumor inhibition activity with minimal side effects.

Two-pore domain (K2P) potassium channels have recently attracted growing interest in the field of cancer research. These channels play an important role in cancer biology specifically for cancer progression, including proliferation, migration, and apoptosis, which makes them an attractive target for novel cancer therapies. Here, we examined the effect of Tetrandrine (Tet), a natural compound known as a channel modulator, which is associated with anticancer activities, as potential drug in this regard. Xenopus oocyte with overexpression of K2P 9.1 (TASK 3) channels has been chosen as model system for this purpose. In order to release Tet and trigger the channels we developed a polymeric magnetic delivery system: Tetrandrine-Magnetite co-loaded poly (lactic-co-glycolic) acid particles. The embedded iron oxide magnetite (Fe3O4) nanoparticles (NPs) allow to inductively heat the particles by applying a high frequency alternating magnetic field, and thus trigger the release of the co-encapsulated Tet. As a proof of concept the nanoparticulate drug delivery system was heated by raising the suspension's temperature proving the temperature dependent release behaviour. Both heating approaches were then successfully applied for measuring the TASK 3 channels current in response to the released drug. It was found that the released Tet amount is sufficient to inhibit the TASK 3 channels in a dose dependent manner. Thus, such a stimulus responsive drug delivery system holds great promise as a novel approach for the treatment of various cancer types such as for the interaction with the two-pore domain potassium channels K2P 9.1., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Aim: To investigate the influence of gold nanoparticle geometry on the biochemical response of Calu-3 epithelial cells., Materials & Methods: Spherical, triangular and hexagonal gold nanoparticles (GNPs) were used. The GNP-cell interaction was assessed via atomic absorption spectroscopy (AAS) and transmission electron microscopy (TEM). The biochemical impact of GNPs was determined over 72 h at (0.0001-1 mg/ml)., Results: At 1 mg/ml, hexagonal GNPs reduced Calu-3 viability below 60%, showed increased reactive oxygen species production and higher expression of proapoptotic markers. A cell mass burden of 1:2:12 as well as number of GNPs per cell (2:1:3) was observed for spherical:triangular:hexagonal GNPs., Conclusion: These findings do not suggest a direct shape-toxicity effect. However, do highlight the contribution of shape towards the GNP-cell interaction which impacts upon their intracellular number, mass and volume dose.