Bioengineered Platelets Combining Chemotherapy and Immunotherapy for Postsurgical Melanoma Treatment: Internal Core-Loaded Doxorubicin and External Surface-Anchored Anti-PD-L1 Antibody Backpacks.

The pivotal factors affecting the survival rate of patients include metastasis and tumor recurrence after the resection of the primary tumor. Anti-PD-L1 antibody (aPD-L1) has promising efficacy but with some side effects for the off-target binding between aPD-L1 and normal tissues. Here, inspired by the excellent targeting capability of platelets with respect to tumor cells, we propose bioengineered platelets (PDNGs) with inner-loaded doxorubicin (DOX) and outer-anchored aPD-L1-cross-linked nanogels to reduce tumor relapse and metastatic spread postoperation. The cargo does not impair the normal physiological functions of platelets. Free aPD-L1 is cross-linked to form nanogels with a higher drug-loading efficiency and is sustainably released to trigger the T-cell-mediated destruction of tumor cells, reversing the tumor immunosuppressive microenvironment. PDNGs can reduce the postoperative tumor recurrence and metastasis rate, prolonging the survival time of mice. Our findings indicate that bioengineered platelets are promising in postsurgical cancer treatment by the tumor-capturing and in situ microvesicle-secreting capabilities of platelets.

Genetic manipulation strategies for ethanol production from bioconversion of lignocellulose waste.

Lignocellulose waste was served as promising raw material for bioethanol production. Bioethanol was considered to be a potential alternative energy to take the place of fossil fuels. Lignocellulosic biomass synthesized by plants is regenerative, sufficient and cheap source for bioethanol production. The biotransformation of lignocellulose could exhibit dual significance-reduction of pollution and obtaining of energy. Some strategies are being developing and increasing the utilization of lignocellulose waste to produce ethanol. New technology of bioethanol production from natural lignocellulosic biomass is required. In this paper, the progress in genetic manipulation strategies including gene editing and synthetic genomics for the transformation from lignocellulose to ethanol was reviewed. At last, the application prospect of bioethanol was introduced.

Surface-anchored tumor microenvironment-responsive protein nanogel-platelet system for cytosolic delivery of therapeutic protein in the post-surgical cancer treatment.

Nanoparticle-anchored platelet systems hold great potential to act as drug carriers in post-surgical cancer treatment due to their intrinsic ability to target the bleeding sites. However, rational design is still needed to further improve its cargo release profiles to meet the cytosolic delivery of therapeutic proteins with intracellular targets. Herein, we developed a tumor microenvironment (TME)-responsive backpack-conjugated platelet system to enhance intracellular protein delivery, thereby significantly inhibiting tumor recurrence after surgery. Specifically, protein nanogels encapsulating GALA and Granzyme B (GrB) are conjugated on the platelet surface via an acid-sensitive benzoic-imine linker through a biorthogonal reaction (GALA-GNGs-P). Taking advantage of wound-tropism of platelets, GALA-GNGs-P could actively accumulate at the surgical trauma and release nanogels in response to acidic TME for promoting deep penetration. Following cellular uptake, the pore-forming peptide GALA helps nanogels escape from lysosome. Subsequently, high glutathione (GSH) concentration in tumor cytoplasm facilitates GrB release from NGs, leading to intense cell apoptosis. GALA-GNGs-P shows remarkable tumor-targeting capability, high cellular uptake, and outstanding lysosomal escaping ability, which can significantly inhibit tumor recurrence in mice models with incomplete tumor resection. Our findings indicate that platelets bioengineered with TME-responsive protein nanogels provide an option to intracellularly deliver therapeutic proteins for the post-surgical treatment of cancer. STATEMENT OF SIGNIFICANCE: Platelet-based drug delivery systems (DDSs) have gained considerable achievements in post-surgical cancer treatment. However, there is no research exploring their potential in realizing the controllable release of cargoes in the acidic tumor microenvironment (TME). Herein, we developed a TME-responsive bioengineered platelet delivery platform (GALA-GNGs-P) for achieving controllable and effective protein intracellular delivery to overcome post-surgical tumor recurrence. Our surface-anchored nanogel-platelet system has the following advantages: (i) improving the loading efficiency of therapeutic proteins, (ii) affecting no physiological function of platelets, (iii) realizing on-demand cargo release in the acidic TME, and (iv) helping proteins escape from endosomal entrapment. Our findings further explored the prospect of cellular backpack system and realized the controllable release of cargoes in the acidic TME.

Novel Fe3O4@metal-organic framework@polymer core-shell-shell nanospheres for fast extraction and specific preconcentration of nine organophosphorus pesticides from complex matrices.

Herein, a novel core-shell-shell magnetic nanosphere denoted as Fe3O4@ZIF-8@polymer was fabricated by sequential in situ self-assembly and precipitation polymerization for effective magnetic solid-phase extraction of nine organophosphorus pesticides (OPPs) from river water, pear, and cabbage samples. The integrated Fe3O4@ZIF-8@polymer featured convenient magnetic separation property and excellent multi-target binding ability. More importantly, the functional polymer coating greatly improved the extraction performance of Fe3O4@ZIF-8 for OPPs, thus facilitating the simultaneous determination of trace OPP residues in real samples. The developed MPSE-LC-MS/MS method exhibited good linearity (R2 ≥ 0.9991) over the concentration range of 0.2-200 µg L-1, low limits of detection of 0.0002-0.005 µg L-1 for river water and 0.006-0.185 µg kg-1 for pear and cabbage, satisfactory precision with relative standard deviations ≤ 9.7% and accuracy with recoveries of 69.5-94.3%. These results highlight that the combination of polymers with MOFs has great potential to fabricate excellent adsorbents for high-throughput analysis of various contaminants in complex matrices.

Exenatide-loaded inside-porous poly(lactic-co-glycolic acid) microspheres as a long-acting drug delivery system with improved release characteristics.

The glucagon-like peptide-1 receptor agonist exenatide (EXT) is an effective treatment for type 2 diabetes. However, this peptide has a short biological half-life and the delayed release characteristic of current formulations limit its clinical application. Herein, we prepared EXT-loaded inside-porous poly(d,l-lactic-co-glycolic acid (PLGA) microspheres with outside layers (EXT-PMS) using a W1/O/W2 emulsion method with a microfluidic technique and its fabrication and formulation conditions were systematically investigated. In vitro dissolution experiments showed that the PLGA concentration, proportion of drug and oil phase, and the number and size of pores strongly affected the release behaviors of EXT-PMS. In vitro, the optimized EXT-PMS with large internal pores exhibited rapid and stable release without a lag phase. In a rat model, subcutaneous administration of the product yielded plasma concentrations of EXT that was sustained for 30 days with low burst and no delayed-release effect. The preparation of inside-porous microspheres is lighting up the development of long-acting drug delivery systems for other drugs with favorable release characteristics.