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Intelligent nanomaterials open up new avenues for realizing safer and more effective combination immunotherapy. Herein, a kind of simple enzymatically cleavable self‐delivery nanoparticles (MA‐pepA‐Ce6 NPs) is developed by conjugating acidic‐sensitive small‐molecule programmed cell death ligand 1 (PD‐L1) inhibitor (Metformin, MET) with photosensitizer (chlorin e6, Ce6) through matrix metalloproteinase‐2 (MMP‐2) cleavable peptide (GPLGVRGDK, pepA). Noticeably, these self‐delivery peptide‐based NPs can circumvent the controversial biosafety facing nanomaterials. Moreover, MA‐pepA‐Ce6 NPs are degraded by overexpressed MMP‐2 in tumor microenvironment (TME) and expose the VRGDK‐Ce6. The exposed VRGDK‐Ce6 shows superior targeting ability towards integrin αvβ3 receptor, ensuring sufficient accumulation and laser‐activated robust antitumor immune effects. Remarkably, the released MET in tumor microenvironment hampers the PD‐L1 expression and augments the antitumor immune response elicited by photodynamics therapy (PDT), thus significantly improving therapeutic outcomes. Overall, this study offers a potential appealing paradigm of synergistic PDT‐triggered immunotherapy by revealing MET‐mediated PD‐L1 downregulation to achieve tumor eradication.

The effective treatment of Alzheimer's disease (AD) is hindered due to the hard blood–brain barrier (BBB) penetration and non‐selective distribution of drugs in the brain. Moreover, the complicated pathological mechanism of AD involves various pathway dysfunctions that limit the effectiveness of a single therapeutic drug. Herein, a dendrigraft poly‐l‐lysines (DGL)‐based siRNA and D peptide (Dp) loaded nanoparticle is designed that could target and penetrate through the BBB, enter the brain parenchyma, and further accumulate at the AD lesion. In this system, T7 peptide, which specifically targets transferrin receptors on the BBB, is linked to DGL via acid‐cleavable long polyethylene glycol (PEG) to achieve high internalization, quick escape from endo/lysosome, and effective transcytosis. Then, the Tet1, which specifically targets diseased neurons, is modified onto DGL by short PEG. After being exposed, Tet1 could drive the nanoparticles to the AD lesion and release the drugs. As a result, the production of β amyloid plaques (Aβ) is inhibited. Neurotoxicity induced by Aβ plaques and tau proten phosphorylation (p‐tau) tangle is also alleviated, and the cognition of AD mice is significantly improved. Overall, this system programmatically targets BBB and neurons, thus, significantly enhances the intracephalic drug accumulation and AD treatment efficacy.

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Solid tumors always exhibit local hypoxia, resulting in the high metastasis and inertness to chemotherapy. Reconstruction of hypoxic tumor microenvironment (TME) is considered a potential therapy compared to directly killing tumor cells. However, the insufficient oxygen delivery to deep tumor and the confronting “Warburg effect” compromise the efficacy of hypoxia alleviation. Herein, we construct a cascade enzyme-powered nanomotor (NM-si), which can simultaneously provide sufficient oxygen in deep tumor and inhibit the aerobic glycolysis to potentiate anti-metastasis in chemotherapy. Catalase (Cat) and glucose oxidase (GOx) are co-adsorbed on our previously reported CAuNCs@HA to form self-propelled nanomotor (NM), with hexokinase-2 (HK-2) siRNA further condensed (NM-si). The persistent production of oxygen bubbles from the cascade enzymatic reaction propels NM-si to move forward autonomously and in a controllable direction along H 2 O 2 gradient towards deep tumor, with hypoxia successfully alleviated in the meantime. The autonomous movement also facilitates NM-si with lysosome escaping for efficient HK-2 knockdown to inhibit glycolysis. In vivo results demonstrated a promising anti-metastasis effect of commercially available albumin-bound paclitaxel (PTX@HSA) after pre-treated with NM-si for TME reconstruction. This cascade enzyme-powered nanomotor provides a potential prospect in reversing the hypoxic TME and metabolic pathway for reinforced anti-metastasis of chemotherapy.

Nano-sized silicon is a potential high energy density anode material for lithium ion batteries.

Silicon/carbon (Si/C) composites have rightfully earned the attention as anode candidates for high-energy-density lithium-ion batteries (LIBs) owing to their advantageous capacity and superior cycling stability, yet their practical application remains a significant challenge. In this study, we report the large-scale synthesis of an intriguing micro/nanostructured pore-rich Si/C microsphere consisting of Si nanoparticles tightly immobilized onto a micron-sized cross-linked C matrix that is coated by a thin C layer (denoted P-Si/C@C) using a low-cost spray-drying approach and a chemical vapor deposition process with inorganic salts as pore-forming agents. The as-obtained P-Si/C@C composite has high porosity that provides sufficient inner voids to alleviate the huge volume expansion of Si. The outer smooth and robust C shells strengthen the stability of the entire structure and the solid−electrolyte interphase. Si nanoparticles embedded in a microsized cross-linked C matrix show excellent electrical conductivity and superior structural stability. By virtue of structural advantages, the asfabricated P-Si/C@C anode displays a high initial Coulombic efficiency of 89.8%, a high reversible capacity of 1269.6 mAh g −1 at 100 mA g −1 , and excellent cycle performance with a capacity of 708.6 mAh g −1 and 87.1% capacity retention after 820 cycles at 1000 mA g −1 , outperforming the reported results of Si/C composite anodes. Furthermore, a low electrode swelling of 18.1% at a high areal capacity of 3.8 mAh cm −2 can be obtained. When assembled into a practical 3.2 Ah cylindrical cell, extraordinary long cycling life with a capacity retention of 81.4% even after 1200 cycles at 1C (3.2 A) and excellent rate performance are achieved, indicating significant advantages for long-life power batteries in electric vehicles.