Photothermal and Acid-Responsive Fucoidan-CuS Bubble Pump Microneedles for Combined CDT/PTT/CT Treatment of Melanoma.

Transdermal cancer therapy faces great challenges in clinical practice due to the low drug transdermal efficiency and the unsatisfactory effect of monotherapy. Herein, we develop a novel bubble pump microneedle system (BPMN-CuS/DOX) by embedding sodium bicarbonate (NaHCO3) into hyaluronic acid microneedles (MNs) loaded with fucoidan-based copper sulfide nanoparticles (Fuc-CuS NPs) and doxorubicin (DOX). BPMN-CuS/DOX can generate CO2 bubbles triggered by an acidic tumor microenvironment for deep and rapid intradermal drug delivery. Fuc-CuS NPs exhibit excellent photothermal effect and Fenton-like catalytic activity, producing more reactive oxygen species (ROS) by photothermal therapy (PTT) and chemodynamic therapy (CDT), which enhances the antitumor efficacy of DOX and reduces the dosage of its chemotherapy (CT). Simultaneously, DOX increases intracellular hydrogen peroxide (H2O2) supplementation and promotes the sustained production of ROS. BPMN-CuS/DOX significantly inhibits melanoma both in vitro and in vivo by the combination of CDT, PTT, and CT. In short, our study significantly enhances the effectiveness of transdermal drug delivery by constructing BPMNs and provides a promising novel strategy for transdermal cancer treatment with multiple therapies.

Agarose oligosaccharide- silver nanoparticle- antimicrobial peptide- composite for wound dressing.

Marine polysaccharides or oligosaccharides have potential to promote wound healing due to their biocompatibility and physicochemical properties. However, microbial infection delays wound healing process, and novel antimicrobial wound dressings are urgently needed. Here, agarose oligosaccharides (AGO) obtained from marine red algae were used as a reducing and stabilizer for green synthesis of silver nanoparticles (AgNPs), and further successfully connected with odorranain A (OA), one of antimicrobial peptides (AMPs), to obtain a novel composite nanomaterial (AGO-AgNPs-OA). Transmission electron microscopy (TEM) and Malvern particle size analyzer showed that AGO-AgNPs-OA was spherical or elliptic with average size of about 100 nm. Circular dichroism (CD) spectroscopy showed that AGO-AgNPs stabilized the α-helical structure of OA. AGO-AgNPs-OA showed stronger anti-bacterial activities than AGO-AgNPs, and had good biocompatibility and significant promoting effect on wound healing. Our data suggest that AMPs conjugated marine oligosaccharides and AgNPs may be effective and safe antibacterial materials for wound therapy.

Alginate-chitosan oligosaccharide-ZnO composite hydrogel for accelerating wound healing.

Moist, breathable and antibacterial microenvironment can promote cell proliferation and migration, which is beneficial to wound healing. Here, we fabricated a novel sodium alginate-chitosan oligosaccharide­zinc oxide (SA-COS-ZnO) composite hydrogel by spontaneous Schiff base reaction, using aldehydated sodium alginate (SA), chitosan oligosaccharide (COS), and zinc oxide (ZnO) nanoparticles, which can provide a moist and antibacterial environment for wound healing. The porosity and swelling degree of SA-COS-ZnO hydrogel are 80% and 150%, respectively, and its water vapor permeability is 682 g/m2/24h. The composite hydrogel showed good biocompatibility to blood cells, 3T3 cells, and 293T cells, and significant antibacterial activity against Escherichia coli, Staphylococcus aureus, Candida albicans, and Bacillus subtilis. Moreover, the hydrogel showed a promoting effect on wound healing in a rat scald model. The present study suggests that marine carbohydrates composite hydrogels are promising in wound care management.

Necroptotic cancer cells-mimicry nanovaccine boosts anti-tumor immunity with tailored immune-stimulatory modality.

Recent breakthroughs in cancer immunotherapy offer new paradigm-shifting therapeutic options for combating cancer. Personalized therapeutic anti-cancer vaccines training T cells to directly fight against tumor cells endogenously offer tremendous benefits in working synergistically with immune checkpoint inhibitors. Biomimetic nanotechnology offers a versatile platform to boost anticancer immunity by efficiently co-delivering optimized immunogenic antigen materials and adjuvants to antigen presenting cells (APC). Necroptotic tumor cells can release danger associated molecule patterns (DAMPs) like heat shock proteins, being more immunogenic than naïve tumor cells. Here, nano-size "artificial necroptotic cancer cell" (αHSP70p-CM-CaP) composing of phospholipid bilayer and a phosphate calcium core was designed as a flexible vaccine platform for co-delivering cancer membrane proteins (CM), DAMPs signal-augmenting element α-helix HSP70 functional peptide (αHSP70p) and CpG to both natural killer (NK) cells and APC. Mechanically, immunogenic B16OVA tumor cells membrane-associated antigens and αHSP70p were reconstituted in artificial outer phospholipid bilayer membrane via one-step hydration and CpG encapsulated in the phosphate calcium core. The resulted αHSP70p-CM-CaP exhibited 30 nm in diameter with the immunogenic membrane proteins reserved in the particles to produce synergistic effect on bone marrow derived dendritic cells maturation and antigen-presentation. Following αHSP70p-CM-CaP vaccination, efficient lymph node trafficking and multi-epitope-T cells response was observed in mice. Vitally, αHSP70p-CM-CaP was also able to induce expansion of IFN-γ-expressing CD8+ T cells and NKG2D+ NK cells subsets. Most promisingly, αHSP70p-CM-CaP vaccination led to the killing of target cells and tumor regression in vivo when combined with anti-PD-1 antibody treatment on mice B16OVA melanoma models. Altogether, we demonstrated proof-of-concept evidence for the feasibility, capability and safety of a nanovaccine platform towards efficient personalized anticancer application.