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Background The interactions between nanoparticles (NPs) and plasma proteins form a protein corona around NPs after entering the biological environment, which provides new biological properties to NPs and mediates their interactions with cells and biological barriers. Given the inevitable interactions, we regard nanoparticle‒protein interactions as a tool for designing protein corona-mediated drug delivery systems. Herein, we demonstrate the successful application of protein corona-mediated brain-targeted nanomicelles in the treatment of glioma, loading them with paclitaxel (PTX), and decorating them with amyloid β-protein (Aβ)-CN peptide (PTX/Aβ-CN-PMs). Aβ-CN peptide, like the Aβ1–42 peptide, specifically binds to the lipid-binding domain of apolipoprotein E (ApoE) in vivo to form the ApoE-enriched protein corona surrounding Aβ-CN-PMs (ApoE/PTX/Aβ-CN-PMs). The receptor-binding domain of the ApoE then combines with low-density lipoprotein receptor (LDLr) and LDLr-related protein 1 receptor (LRP1r) expressed in the blood–brain barrier and glioma, effectively mediating brain-targeted delivery. Methods PTX/Aβ-CN-PMs were prepared using a film hydration method with sonication, which was simple and feasible. The specific formation of the ApoE-enriched protein corona around nanoparticles was characterized by Western blotting analysis and LC–MS/MS. The in vitro physicochemical properties and in vivo anti-glioma effects of PTX/Aβ-CN-PMs were also well studied. Results The average size and zeta potential of PTX/Aβ-CN-PMs and ApoE/PTX/Aβ-CN-PMs were 103.1 nm, 172.3 nm, 7.23 mV, and 0.715 mV, respectively. PTX was efficiently loaded into PTX/Aβ-CN-PMs, and the PTX release from rhApoE/PTX/Aβ-CN-PMs exhibited a sustained-release pattern in vitro. The formation of the ApoE-enriched protein corona significantly improved the cellular uptake of Aβ-CN-PMs on C6 cells and human umbilical vein endothelial cells (HUVECs) and enhanced permeability to the blood–brain tumor barrier in vitro. Meanwhile, PTX/Aβ-CN-PMs with ApoE-enriched protein corona had a greater ability to inhibit cell proliferation and induce cell apoptosis than taxol. Importantly, PTX/Aβ-CN-PMs exhibited better anti-glioma effects and tissue distribution profile with rapid accumulation in glioma tissues in vivo and prolonged median survival of glioma-bearing mice compared to those associated with PMs without the ApoE protein corona. Conclusions The designed PTX/Aβ-CN-PMs exhibited significantly enhanced anti-glioma efficacy. Importantly, this study provided a strategy for the rational design of a protein corona-based brain-targeted drug delivery system. More crucially, we utilized the unfavorable side of the protein corona and converted it into an advantage to achieve brain-targeted drug delivery. Graphical Abstract

Cancer-associated fibroblasts (CAFs), an important type of stromal cells in the tumor microenvironment (TME), are responsible for creating physical barriers to drug delivery and penetration in tumor tissues. Thus, effectively downregulating CAFs to destroy the physical barrier may allow enhanced penetration and accumulation of therapeutic drugs, thereby improving therapeutic outcomes. Herein, a matrix metalloproteinase (MMP)-triggered dual-targeting hybrid micelle-inliposome system (RPM@NLQ) was constructed to sequentially deliver quercetin (Que) and paclitaxel (PTX) for fibrotic TME remodeling and chemotherapy potentiation. Specifically, antifibrotic Que and small-sized RGD-modified micelles containing PTX (RPM) were co-encapsulated into MMP-sensitive liposomes, and the liposomes were further adorned with the NGR peptide (NL) as the targeting moiety. The resulting RPM@NLQ first specifically accumulated at the tumor site under the guidance of the NGR peptide after intravenous administration and then released Que and RPM in response to the extensive expression of MMP in the TME. Subsequently, Que was retained in the stroma to remarkably downregulate fibrosis and decrease the stromal barrier by downregulating Wnt16 expression in CAFs, which further resulted in a significant increase of RPM for deeper tumor. Thus, RPM could precisely target and kill breast cancer cells locally. Consequently, prolonged blood circulation, selective cascade targeting of tumor tissue and tumor cells, enhanced penetration, and excellent antitumor efficacy have been demonstrated in vitro and in vivo. In conclusion, as-designed sequential delivery systems for fibrotic TME remodeling and chemotherapy potentiation may provide a promising adjuvant therapeutic strategy for breast and other CAF-rich tumors.

The development of hollow and porous materials is essential for effective energy storage and conversion owing to their facile transport of electrons and ions. Herein, through a facile low-temperature thermal decomposition reaction of ZIF-67 crystals, hollow Co 3 O 4 nanocages composed of numerous nanoparticles with a porous structure are prepared. These hollow and porous Co 3 O 4 nanocages (Co 3 O 4 HPCs) possess a pore size distribution between 20 and 60 nm and a large Brunauer−Emmett−Teller surface area of 211.79 m 2 g −1 . Benefitting from the large surface area, a maximum specific capacitance of 140.0 F g −1 can be calculated. Furthermore, the assembled Co 3 O 4 HPCs//activated carbon hybrid supercapacitor can deliver an energy density of 19.8 W h kg −1 and 97.3% capacitance retention during 5000 cycles. As a result of good electrochemical performance of these Co 3 O 4 HPCs, they can be a promising electrode for supercapacitors.

Hollow nanostructures with enlarged surface areas are highly attractive electrode materials for supercapacitors. In this work, the size-dependent synthesis of hollow Co3O4 nanocubes via a facile ionic exchange reaction between Co-Fe Prussian blue analogues (PBAs) and alkali solution is reported. By adjusting the concentration of sodium citrate to control the reaction kinetics during nucleation and growth, four different sizes of Co-Fe PBAs were synthesized. It was also found that a Co-Fe PBA of about 140 nm can be easily converted into a well-defined internal hollow structure, while Co-Fe PBAs with smaller or larger sizes are challenged in generating a hollow structure. Benefitting from the inner voids and thin shell architecture, the derived hollow Co3O4 nanocubes exhibit a high specific capacity of 296.6C cm−2 at 2 mA cm−2, and a rate capability of 64.5% when the current density is increased to 60 mA cm−2. Furthermore, a hybrid supercapacitor (HSC) was fabricated with hollow Co3O4 nanocubes as the cathode and activated carbon as the anode, respectively. The HSC provided a maximum energy density of 14.1 Wh kg−1 at 464.7 W kg−1. Moreover, it retained the excellent cycling stability of 85.7% of the original capacity over 5000 continuous charging and discharging processes.