Co-delivery of Peptide Neoantigens and Stimulator of Interferon Genes Agonists Enhances Response to Cancer Vaccines
Cancer vaccines targeting patient-specific neoantigens have emerged as a promising strategy for improving responses to immune checkpoint blockade. However, neoantigenic peptides are poorly immunogenic and inept at stimulating CD8+ T cell responses, motivating a need for new vaccine technologies that enhance their immunogenicity. The stimulator of interferon genes (STING) pathway is an endogenous mechanism by which the innate immune system generates an immunological context for priming and mobilizing neoantigen-specific T cells. Owing to this critical role in tumor immune surveillance, a synthetic cancer nanovaccine platform (nanoSTING-vax) was developed that mimics immunogenic cancer cells in its capacity to efficiently promote co-delivery of peptide antigens and the STING agonist, cGAMP. The co-loading of cGAMP and peptides into pH-responsive, endosomolytic polymersomes promoted the coordinated delivery of both cGAMP and peptide antigens to the cytosol, thereby eliciting inflammatory cytokine production, co-stimulatory marker expression, and antigen cross-presentation. Consequently, nanoSTING-vax significantly enhanced CD8+ T cell responses to a range of peptide antigens. Therapeutic immunization with nanoSTING-vax, in combination with immune checkpoint blockade, inhibited tumor growth in multiple murine tumor models, even leading to complete tumor rejection and generation of durable antitumor immune memory. Collectively, this work establishes nanoSTING-vax as a versatile platform for enhancing immune responses to neoantigen-targeted cancer vaccines.
SHAE, Daniel et al. Co-Delivery of Peptide Neoantigens and Stimulator of Interferon Genes (STING) Agonists Enhances Response to Cancer Vaccines. ACS nano, 2020.
Ionic liquid-mediated delivery of insulin to buccal mucosa
Buccal drug delivery offers a potential non-invasive means of delivering therapeutics to patients. Despite the promise, the feasibility of transporting proteins and peptides into systemic circulation from buccal administration remains a daunting challenge. Here, we report the fabrication of a biodegradable polymeric patch for buccal delivery of insulin using chitosan as the mucoadhesive matrix and ionic liquids (ILs)/deep eutectic solvent (DES) as the transport facilitator. Insulin is mixed with ILs/DES made from Choline and Geranic acid (CAGE) to form a viscoelastic CAGE gel and sandwiched between two layers of a biodegradable polymer. The rheological properties of the CAGE gel were dominated by the elastic modulus and suggested a solid-like viscoelastic behavior. CAGE induced a 7-fold increase in the cumulative insulin transport across the ex vivo porcine buccal tissue (~26% of loaded insulin) which was also confirmed by confocal microscopy. The CAGE/insulin patches placed in the rat buccal pouch in vivo lowered blood glucose levels in a dose-dependent manner (up to 50% drop recorded) with no obvious tissue damage at the application site. The pharmacokinetic performance of the delivered insulin indicated a sustained profile as serum insulin levels plateaued after 3 h for the duration of study. The safety and efficacy of the polymeric patch using insulin as a model drug holds significant promise as a platform technology to deliver injectables through the buccal route.
VAIDYA, A. and MITRAGOTRI, S. Ionic liquid-mediated delivery of insulin to buccal mucosa. Journal of Controlled Release, 2020.
Delivery of a model lipophilic membrane cargo to bone marrow via cell-derived microparticles
Bone marrow (BM) is the central immunological organ and the origin of hematological diseases. Efficient and specific drug delivery to the BM is an unmet need. We tested delivery of fluorescent indocarbocyanine lipids (ICLs, DiR, DiD, DiI) as a model lipophilic cargo. Systemically injected T-lymphocyte cell line Jurkat delivered ICLs to the BM more efficiently than erythrocytes, and more selectively than PEGylated liposomes. Near infrared imaging showed that the delivery was restricted to the BM, lungs, liver and spleen, with no accumulation in the kidneys, brain, heart, intestines, fat tissue and pancreas. Following systemic injection of ICL-labeled cells in immunodeficient or immunocompetent mice, few cells arrived in the BM intact. However, between 5 and 10% of BM cells were ICL-positive. Confocal microscopy of intact BM confirmed that ICLs are delivered independently of the injected cells. Flow cytometry analysis showed that the lipid accumulated in both CD11b + and CD11b- cells, and in hematopoietic progenitors. In a xenograft model of acute myeloid leukemia, a single injection of 10 million Jurkat cells delivered DiD to ~15% of the tumor cells. ICL-labeled cells disappeared from blood almost immediately post-intravenous injection, but numerous cell-derived microparticles continued to circulate in blood. The microparticle particle formation was not due to the ICL labeling or complement attack and was observed after injection of both syngeneic and xenogeneic cells. Injection of microparticles produced in vitro from Jurkat cells resulted in a similar ICL delivery as the injection of intact Jurkat cells. Our results demonstrate a novel delivery paradigm wherein systemically injected cells release microparticles that accumulate in the BM. In addition, the results have important implications for studies involving systemically administered cell therapies.
YANG, Chunyan et al. Delivery of a model lipophilic membrane cargo to bone marrow via cell-derived microparticles. Journal of Controlled Release, 2020.
Cold plasma combined with liposomal ethanolic coconut husk extract: A potential hurdle technology for shelf-life extension of Asian sea bass slices packaged under modified atmosphere
The influence of cold plasma (CP) generated using the mixed gases (oxygen, carbon dioxide argon: 10: 60:30) for 5 min in combination with ethanolic coconut husk extract (ECHE) in either free or liposomal encapsulated form (LE-ECHE) at a concentration of 400 ppm on shelf-life of refrigerated Asian sea bass slices (ASBS) packaged under modified atmosphere was studied.
LE-ECHE was prepared using 60 μmol/ml lipid phase containing soybean phosphatidylcholine/cholesterol mixture (4:1, mol ratio) and 1% ECHE. ECHE or LE-ECHE were dissolved in a minimum volume of water and mixed with Asian seabass slices to obtain the final concentration of 400 ppm. Total viable mesophilic bacteria count in CP treated ASBS, particularly those enriched with ECHE or LE-ECHE (EC400-CP and LEC400-CP, respectively) were at least 1 log CFU/g lower than that of the control. Protein and lipid oxidation were lower in EC400-CP and LEC400-CP as compared to those treated with CP only. Discoloration of slices mediated by ECHE was solved by encapsulating ECHE in liposome. Therefore, CP combined with LE-ECHE, was an effective hurdle approach for shelf-life extension of ASBS for more than 18 days at 4 °C.
OLATUNDE, Oladipupo Odunayo; BENJAKUL, Soottawat; VONGKAMJAN, Kitiya. Cold plasma combined with liposomal ethanolic coconut husk extract: A potential hurdle technology for shelf-life extension of Asian sea bass slices packaged under modified atmosphere. Innovative Food Science & Emerging Technologies, p. 102448, 2020.
Carbon dots from dragonfruit peels as growth-enhancer on ipomoea aquatica vegetable cultivation
C-dots have been successfully synthesised from the dragon fruit peels and were applied as growth-enhancer for Ipomoea aquatica vegetable cultivation. C-dots were obtained from the extract of dragon fruit peels via microwave radiation for 5 to 30 min. Two typical peaks of betalains in the dragon fruit peel extract experienced alteration. When increasing the microwave radiation time, typical peak intensity at 543 nm is decreased and peak intensity at 393 nm is increased. C-dots from dragon fruit peels have particle size in range of 8–25 nm. The optimum C-dots have been produced from 20-min microwave radiation with power of 230 watt. The emission of C-dots appeared at wavelength of 450 nm. The obtained C-dots are capable of binding nitrogen-phosphor-potassium (NPK) fertiliser and act as nutrients carrier. C-dots were then directly supplemented to Ipomoea aquatica vegetable to figure out their influence on plant growth. The supplementation of C-dots was varied by their volume fraction. The effect of C-dots was analysed by measuring the growth rate of plant. This study confirmed that the supplementation of C-dots could enhance the growth of Ipomoea aquatica vegetable. This study denoted that C-dots from dragon fruit peel extracts successfully act as a growth enhancer to increase vegetable yields.
AJI, Mahardika Prasetya et al. Carbon dots from dragonfruit peels as growth-enhancer on ipomoea aquatica vegetable cultivation. Advances in Natural Sciences: Nanoscience and Nanotechnology, v. 11, n. 3, p. 035005, 2020.
Polyethylenimine-functionalized polyacrylonitrile anion exchange fiber as a novel adsorbent for rapid removal of nitrate from wastewater
The development of an adsorbent with high adsorption ability and favorable cyclic regeneration performance for the removal of nitrate residues from wastewater is a task of vital importance. To this end, polyacrylonitrile fiber (PANF) was modified with polyethyleneimine (PEI), and alkyl groups were then introduced around the active amine groups to prepare three polymer-based anion exchange fibers (PAN-PEI-3C, PAN-PEI-5C, and PAN-PEI-8C). The novel fibers were characterized using techniques such as scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), Fourier-transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and thermogravimetric analysis (TGA). The adsorption isotherms of the fibers were best fitted by the Langmuir model, and PAN-PEI-5C exhibited a higher adsorption amount of nitrate (31.32 mg/g) than the other adsorbents. The equilibrium was reached expeditiously (within 10 min), and both pseudo-first-order and pseudo-second-order models could well describe the adsorption kinetics. More attractively, the saturated PAN-PEI-5C could be eluted using a low-concentration (0.3 M) NaCl solution, without any sharp loss of adsorption amount for five consecutive cycles in the presence of dissolved organic matter (DOM). Furthermore, PAN-PEI-5C could effectively adsorb low-concentration nitrate from real secondary effluents in a fixed-bed column experiment. Our work provides a promising and low-cost material for the removal of nitrate residues in practical applications.
SUN, Yue; ZHENG, Weisheng. Polyethylenimine-functionalized polyacrylonitrile anion exchange fiber as a novel adsorbent for rapid removal of nitrate from wastewater. Chemosphere, p. 127373, 2020.