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Due to the complexity and heterogeneity in the tumor microenvironment, the efficacy of breast cancer treatment has been significantly impeded. Here, we established a living system using an engineered M13 bacteriophage through chemical cross-linking and biomineralization to remodel the tumor microenvironment. Chemically cross-linking of the engineered bacteriophage gel (M13 Gel) could in situ synthesize photothermal palladium nanoparticles (PdNPs) on the pVIII capsid protein to obtain M13@Pd Gel. In addition, NLG919 was further loaded into a gel to form (M13@Pd/NLG gel) for down-regulating the expression of tryptophan metabolic enzyme indoleamine 2,3-dioxygenase 1 (IDO1). Both in vitro and in vivo studies showed that the M13 bacteriophage served not only as a cargo-loaded device but also as a self-immune adjuvant, which induced the immunogenic death of tumor cells effectively and down-regulated IDO1 expression. Such a bioactive gel system constructed by natural living materials could reverse immunosuppression and significantly improve the anti-breast cancer response.

Multiple biological barriers in solid tumors severely restrict the penetration of nanomedicines, which is a main cause for therapeutic failure in traditional tumor treatment. Here, a tumor-specific nanogenerator of peroxynitrite (ONOO - ), prepared by loading cisplatin and sodium nitroprusside into poly(d,l-lactide- co -glycolide) polymersomes, was designed to improve drug delivery and enhance tumor chemotherapy. After a cascade of nicotinamide adenine dinucleotide phosphate oxidases catalysis and glutathione reduction, the nanogenerator, namely, PMCS, could selectively induce the generation of ONOO - in tumor. The generated ONOO - could not only strengthen vascular permeability significantly but also improve the accumulation and penetration of PMCS in tumor by activating matrix metalloproteinases-mediated degradation of extracellular matrix. Along with endocytosis, PMCS released cisplatin to induce tumor cell apoptosis. Moreover, free cisplatin liberated from dead cells infected neighboring tumor cells quickly via ONOO - -mediated up-regulated copper transporter 1, further amplifying chemotherapeutic efficacy. This study advances ONOO - as a potent modality to address the main issues of therapeutic delivery, including but not limited to chemotherapy.

Immunotherapy has provided a promising strategy for the treatment of cancers. However, even in tumors with high antigen burdens, the systemic inhibition of the antigen presentation still greatly restricts the application of immunotherapy. Here, we construct a tumor protein-engineering system based on the functional tripeptide, Asp-Phe-Tyr (DFY), which can automatically collect and deliver immunogenetic tumor proteins from targeted cells to immune cells. Through a tyrosinase-catalyzed polymerization, the DFY tripeptide selectively accumulates in tyrosinase high-expressed melanoma cells. Then quinone-rich intermediates are covalently linked with tumor-specific proteins by Michael addition and form tumor protein-carried microfibers that could be engulfed by antigen-presenting cells and exhibited tumor antigenic properties for boosting immune effect. In melanoma cells with deficient antigen presentation, this system can successfully enrich and transport tumor antigen-containing proteins to immune cells. Furthermore, in the in vivo study on murine melanoma, the transdermal delivery of the DFY tripeptide suppressed the tumor growth and the postsurgery recurrence. Our findings provide an avenue for the regulation of the immune system on an organism by taking advantage of certain polymerization reactions by virtue of chemical biology.

A universal strategy was reported that enables functional group-capped nanostructures with various morphologies and compositions to be coated by porphyrin metal-organic framework (MOF). Based on the nanostructure-induced heterogeneous nucleation, the controlled growth of MOF shell on the surface of nanostructures can be realized. It was demonstrated that this modification strategy can realize controlled growth of porphyrin MOF on a series of organic and inorganic nanostructures, such as polydopamine (PDA) nanoparticles, PDA@Pt nanoparticles, graphene oxide sheets, and Au nanorods. The as-prepared composites exhibit excellent catalytic and optical properties that originate from the nanostructure as well as the coated porphyrin MOF. We further explored the potential applications of PDA@MOF and PDA@Pt@MOF in nanomedicine and photocatalysis.

Chymosin-induced coagulation of individual milk proteins during incubation at 30 °C was investigated using a proteomic approach. The addition of chymosin (0.006 units/mL) caused the milk proteins to coagulate after a 3 h incubation period. Approximately 88% of the milk proteins were coagulated into the milk pellet fraction, and the protein concentration of the milk supernatant fraction (MSF) decreased from 29.88 ± 0.12 to 3.74 ± 0.13 mg/mL. SDS-PAGE analysis showed that α(S)-, β- and κ-caseins in the MSF were almost depleted and that the total intensity of the protein bands corresponding to α(S)-caseins (α(S1) and α(S2)), β-casein, and κ-casein decreased from 1088.0, 901.5, and 617.0 area units to 6.9, 6.1, and 5.2 area units, respectively. Two-dimensional electrophoresis analysis indicated that α(S1)-, α(S2)-, β-, and κ-casein and a fraction of the β-lactoglobulin and serum albumin were found in the MSF following incubation with chymosin.