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Overcoming multiple barriers to deliver macromolecular drugs is an urgent challenge for glioma treatment. Herein, a strategy of protein corona-regulation synergizing with photoactivation based on T10 peptide-modified and indocyanine green (ICG)-loaded dendrigraft poly-L-lysines was proposed to augment prime editing therapy of glioma. First, the modified T10 peptide could escape the interference barrier of protein crown in blood via its specific binding with endogenous transferrin, thus crossing the blood-brain barrier (BBB) and achieving the targeting recognition of glioma cells. Next, the loaded ICG could weaken the tumor stromal barrier, decrease the cell membrane barrier and escape the lysosomal degradation/autophagy barrier via its photothermal and photodynamic effects. Subsequently, a therapeutic gene that could downregulate p-ERK1/2 for tumor growth inhibition and immunoregulation could be effectively delivered into the glioma cells. The glioma-targeted photo-gene combined immunotherapy effectively inhibit the glioma growth, especially co-dosing with the PD-1 antibody., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Nondestructive penetration of the blood-brain barrier (BBB) to specifically prevent iron deposition and the generation of reactive oxygen species (ROS) shows great potential for treating Parkinson's disease (PD). However, effective agents with distinct mechanisms of action remain scarce. Herein, a N-doping carbon dot (CD) emitting red light was prepared, which can sacrifice ROS and produce nitric oxide (NO) owing to its surface N-involved groups conjugated to the sp 2 -hybrided π-system. Meanwhile, CD can chelate iron ions, thus depressing the catalytic Fe cycle and *OH detaching to inhibit the Fenton reaction. By modifying lactoferrin (Lf) via polyethylene glycol (PEG), the resulting CD-PEG-Lf (CPL) can nondestructively cross the BBB, targeting the dopaminergic neurons via both NO-mediated reversible BBB opening and Lf receptor-mediated transportation. Accordingly, it can serve as an antioxidant, reducing oxidative stress via its unique iron chelation, free radical sacrificing, and synergy with iron reflux prevention originating from Lf. Thus, it can significantly reduce brain inflammation and improve the behavioral performance of PD mice. Additionally, CPL can image the PD via its red fluorescence. Finally, this platform can be metabolized out of the brain through cerebrospinal fluid circulation without causing obvious side effects, promising a robust treatment for PD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Cell membrane is crucial for the cellular activities, and any disruption to it may affect the cells. It is demonstrated that cell membrane perforation is associated with some biological processes like programmed cell death (PCD) and infection of pathogens. Specific developments make it a promising technique to perforate the cell membrane controllably and precisely. The pores on the cell membrane provide direct pathways for the entry and exit of substances, and can also cause cell death, which means reasonable utilization of cell membrane perforation is able to assist intracellular delivery, eliminate diseased or cancerous cells, and bring about other benefits. This review classifies the patterns of cell membrane perforation based on the mechanisms into 1) physical patterns, 2) biological patterns, and 3) chemical patterns, introduces the characterization methods and then summarizes the functions according to the characteristics of reversible and irreversible pores, with the aim of providing a comprehensive summary of the knowledge related to cell membrane perforation and enlightening broad applications in biomedical science., (© 2024 Wiley‐VCH GmbH.)

Addressing the urgent need to prevent breast cancer postoperative recurrence and brain metastasis, Fe-metal organic framework (MOF)-coated hollow mesoporous organosilica nanoparticles (HMON) with tumor microenvironment dual-responsive degradability were prepared to encapsulate doxorubicin (DOX), formulating a tissue-adhesive nanosuspension for perioperative topical medication. This nanosuspension can not only retain the sustainably released drug in the postoperative residual tumor sites but also enhance the intracellular oxidative stress of tumors for remarkable tumor ferroptosis. Interestingly, the nanosuspension can act as an immune amplifier, which could not only stimulate DC cells to secrete chemokines for T cell recruitment but also elevate antigen exposure to facilitate the antigen presentation in lymph nodes. Thus, this nanosuspension could significantly activate antitumor immune responses in both in situ tumors and metastatic encephaloma for enhanced immunotherapy. In conjunction with the clinical PD-1 antibody, the locally administered nanosuspension could achieve an advanced therapeutic outcome for inhibiting postoperative recurrence and metastasis.

mRNA therapeutics have emerged as powerful tools for cancer immunotherapy in accordance with their superiority in expressing all sequence-known proteins in vivo. In particular, with a small dosage of delivered mRNA, antigen-presenting cells (APCs) can synthesize mutant neo-antigens and multi-antigens and present epitopes to T lymphocytes to elicit antitumor effects. In addition, expressing receptors like chimeric antigen receptor (CAR), T-cell receptor (TCR), CD134, and immune-modulating factors including cytokines, interferons, and antibodies in specific cells can enhance immunological response against tumors. With the maturation of in vitro transcription (IVT) technology, large-scale and pure mRNA encoding specific proteins can be synthesized quickly. However, the clinical translation of mRNA-based anticancer strategies is restricted by delivering mRNA into target organs or cells and the inadequate endosomal escape efficiency of mRNA. Recently, there have been some advances in mRNA-based cancer immunotherapy, which can be roughly classified as modifications of the mRNA structure and the development of delivery systems, especially the lipid nanoparticle platforms. In this review, the latest strategies for overcoming the limitations of mRNA-based cancer immunotherapies and the recent advances in delivering mRNA into specific organs and cells are summarized. Challenges and opportunities for clinical applications of mRNA-based cancer immunotherapy are also discussed., Competing Interests: The authors declare no conflicts of interest. Wei Tao is a member of the Exploration editorial board., (© 2023 The Authors. Exploration published by Henan University and John Wiley & Sons Australia, Ltd.)

Synergizing the sensitive circulating tumor cell (CTC) capture, detection, release and the specific magnetic resonance/fluorescence (MR/FL) imaging for accurate cancer diagnosis is of great importance for cancer treatment. Herein, EcoR1-responsive complementary pairing of two ssDNA with a fluorescent P 0 aptamer, which can specifically bind with the overexpressed MUC1 protein on cancer cells, was covalently modified to SiO 2 @C-coated magnetic nanoparticles for preparing a special nanoparticle-mediated FL turn-on aptasensor (FSC-D-P 0 ). This aptasensor can selectively capture/enrich CTC and thus achieve sensitive CTC detection/imaging in even the blood due to its stable targeting, unique magnetic properties and the regulated interactions between the quencher and the fluorescent groups. Meanwhile, FSC-D-P 0 can release the captured CTC for further downstream analysis upon the EcoR1 enzyme-triggered cleavage of the double-stranded DNA (dsDNA). Most importantly, this aptasensor can distinctly avoid false positivity of MRI via multiple targeting mechanisms. Thus, the sensitive CTC capture, detection, release and accurate MR/FL imaging were synergistically combined into a single platform with good biocompatibility, promising a robust pattern for clinical tumor diagnosis in vitro and in vivo., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Diabetes immunity-modulated wound treatment in response to the varied microenvironments at different stages remains an urgent challenge. Herein, glucose oxidase (GOx) and quasi-amorphous Fe 2 O 3 are co-incorporated into Zn-MOF nanoparticle (F-GZ) for cascade enzyme catalytic activities, where not only the high blood glucose in the wound is consumed via the GOx catalysis, but also the effective anti-bacteria is achieved via the degradedly released Zn 2+ synergistically with the catalytically produced ·OH during the bacterial infection period with the low pH microenvironment. Simultaneously, the reactive oxygen species scavenging and hypoxia relief is realized via catalyzing H 2 O 2 to produce O 2 at the relatively elevated pH environment during the wound recovery period. Subsequently, a multifunctional hydrogel with injectable, self-healing and hemostasis abilities, as well as uniformed F-GZ loading is prepared via the copolymerization reaction. This hydrogel behaves as F-GZ but reduces the toxic effects, which thus accelerates the diabetic wound healing. More importantly, this hydrogel is found to modulate the diabetes immunity possibly mediated via the released Zn 2+ , which thus contributes to the recovered pancreatic islet functions with improved glucose tolerance and increased insulin secretion for enhanced diabetic wound treatments. This work initiates a new strategy for simultaneous diabetic wound management and also suggests a potential way for diabetic immunity modulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Overcoming blood-brain barrier (BBB) for precise glioma diagnosis remains an urgent challenge due to its peculiar location in central nervous system (CNS). Herein, polymer-coated carbon nanodots with high hydrophilicity were facilely married with Gd-DTPA to construct a dual-modal imaging system (NCDDG). This system was demonstrated with obviously decreased toxicity and enhanced magnetic resonance imaging (MRI) ability compared to traditional Gd-DTPA. Meanwhile, NCDDG reserved the bright fluorescence of biocompatible carbon nanodots with increased spatial resolution. Attributed to small size and hydrophilic polymer coating, NCDDG was capable of overcoming the BBB and permeating leaky microvascular walls into surrounding glioma tissues via prolonged in vivo circulation and enhanced retention effect. As a result, dual 1 -modal targeted MR/fluorescence imaging of glioma was synergistically achieved with high sensitivity and resolution. This work promised a potential contrast agent for sensitive clinical diagnosis of glioma., (Copyright © 2018. Published by Elsevier B.V.)

In this report, we present a mesoporous carbon nanosphere that can target drugs to tumors and image tumor biomarkers. A single-strand DNA (P 0 aptamer) aptavalve was capped on the surface of doxorubicin-loaded oxide mesoporous carbon nanospheres (Dox-OMCN-P 0 ) through π-π stacking for real-time imaging-guided on-demand targeting drug delivery. The Dox-OMCN-P 0 could not only realize the detection of MUC1 tumor marker with a wide linear range (0.1 - 10.6 μmol/L) and a low detection limit (17.5 nmol) based on different apparatuses, but also achieve in-situ targeting imaging of cellular MUC1 concentration in vitro and in vivo via "off-on" fluorescence biosensing. Much attractively, as a real-time feedback of the diagnostic/imaging outcomes, Dox-OMCN-P 0 accomplished the on-demand targeting drug delivery in quantitative response to MUC1. Controllable chemotherapy with sustained release and pH-sensitiveness, together with the potential photothermal therapy, were also clearly demonstrated. This is a simple but advanced platform, which could well achieve the real-time switchable imaging of cellular mucin for targeting cancer therapy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

A facile one-step solvothermal method was developed for the homogeneously confined growth of ultra-small (∼1.5 nm) and monodispersed 2H phase MoS2 nanodots into mesoporous silica nanoparticles (MSNs).