Ischemic Microenvironment-Targeted Bioinspired Lipoprotein Sequentially Penetrates Cerebral Ischemic Lesions to Rescue Ischemic Stroke.

Reperfusion injury represents a significant impediment to recovery after recanalization in an ischemic stroke and can be alleviated by neuroprotectants. However, inadequate drug delivery to ischemic lesions impairs the therapeutic effects of neuroprotectants. To address this issue, an ischemic microenvironment-targeted bioinspired lipoprotein system encapsulating lipoic acid (LA@PHDL) is herein designed to sequentially penetrate ischemic lesions and be readily taken up by neurons and microglia. In transient middle cerebral artery occlusion (tMCAO) mouse models, LA@PHDL accumulates rapidly and preferentially in the ischemic brain, with a 2.29-fold higher than the nontargeted nanoplatform in the early stage. Furthermore, LA@PHDL effectively restores neurological function, reduces infarct volume to 17.70%, prevents brain cell necrosis and apoptosis, and attenuates inflammation in tMCAO mouse models. This design presents new opportunities for delivering neuroprotectants to cerebral ischemic lesions to improve the outcome of an ischemic stroke.

Biomimetic Integrated Nanozyme for Flare and Recurrence of Gouty Arthritis.

Flare and multiple recurrences pose significant challenges in gouty arthritis. Traditional treatments provide temporary relief from inflammation but fail to promptly alleviate patient pain or effectively prevent subsequent recurrences. It should also be noted that both anti-inflammation and metabolism of uric acid are necessary for gouty arthritis, calling for therapeutic systems to achieve these two goals simultaneously. In this study, we propose a biomimetic integrated nanozyme, HMPB-Pt@MM, comprising platinum nanozyme and hollow Prussian blue. It demonstrates anti-inflammatory properties by eliminating reactive oxygen species and reducing infiltration of inflammatory macrophages. Additionally, it rapidly targets inflamed ankles through the camouflage of macrophage membranes. Furthermore, HMPB-Pt@MM exhibits urate oxidase-like capabilities, continuously metabolizing locally elevated uric acid concentrations, ultimately inhibiting multiple recurrences of gouty arthritis. In summary, HMPB-Pt@MM integrates ROS clearance with uric acid metabolism, offering a promising platform for the treatment of gouty arthritis.

Hyperthermia/glutathione-triggered ferritin nanoparticles amplify the ferroptosis for synergistic tumor therapy.

Breast cancer is the most diagnosed malignancy in women globally, and drug resistance is among the major obstacles to effective breast cancer treatment. Emerging evidence indicates that photothermal therapy and ferroptosis are both promising therapeutic techniques for the treatment of drug-resistant breast tumors. In this study, we proposed a thermal/ferroptosis/magnetic resonance imaging (MRI) triple functional nanoparticle (I@P-ss-FRT) in which ferritin, an iron storage material with excellent cellular uptake capacity, was attached via disulfide bonds onto polydopamine coated iron oxide nanoparticle (I@P) as photothermal transduction agent and MRI probe. I@P-ss-FRT converted the near-infrared light (NIR) into localized heat which accelerated the release of ferrous ions from ferritin accomplished by glutathione reduction and subsequently induced ferroptosis. The drug-resistant cancer cell lines exhibited a more significant uptake of I@P-ss-FRT and sensitivity to PTT/ferroptosis compared with normal cancer cell lines. In vivo, I@P-ss-FRT plus NIR displayed the best tumor-killing potential with inhibitory rate of 83.46 %, along with a decline in GSH/GPX-4 content and an increase in lipid peroxides generation at tumor sites. Therefore, I@P-ss-FRT can be applied to combat drug-resistant breast cancer.

Enhancement of cancer immunotherapy using CRT valgus tumor cell membranes coated bacterial whole peptidoglycan combined with radiotherapy.

Immunotherapy has achieved some success in preclinical and clinical studies, but the immunosuppressive tumor microenvironment (TME) leads to a low response rate of this therapy. In this paper, we describe a calreticulin (CRT) valgus CT-26 tumor cell membranes-coated bacterial whole peptidoglycan (WPG) from P. aeruginosa (CPW/SR) with a high rate of the STING agonist loading. In the construct, WPG from P. aeruginosa (P.WPG) was used as a carrier with the immunoadjuvant function while synergistically promoting the maturation of dendritic cells (DCs) through the delivery of the STING agonist SR-717. CRT valgus tumor cell membranes were identified and internalized by DCs via CRT on the surface. In addition, this construct was able to reverse the immunosuppressive TME in vivo and achieve synergies with radiotherapy by creating a personalized tumor vaccine, therefore achieving more resultful antitumor efficacy. In conclusion, CPW/SR constructed in this paper provides a new approach for achieving efficient cancer immunotherapy and combination therapy.