Showing papers by "Na Kong published in 2023"

Nanoheterojunction‐Mediated Thermoelectric Strategy for Cancer Surgical Adjuvant Treatment and β‐Elemene Combination Therapy

Abstract: As an indispensable strategy for tumor treatment, surgery may cause two major challenges: tumor recurrence and wound infection. Here, a thermoelectric therapeutic strategy is provided as either an independent cancer therapy or surgical adjuvant treatment. Bi0.5Sb1.5Te3 (BST) and Bi2Te2.8Se0.2 (BTS) nanoplates composed of Z‐scheme thermoelectric heterojunction (BST/BTS) are fabricated via a two‐step hydrothermal processes. The contact between BST and BTS constructs an interfacial electric field due to Fermi energy level rearrangement, guiding electrons in the conductive band (CB) of BTS combine with the holes in the valance band (VB) of BST, leaving stronger reduction/oxidation potentials of electrons and holes in the CB of BST and the VB of BTS. Moreover, under a mild temperature gradient, another self‐built‐in electric field is formed facilitating the migration of electrons and holes to their surfaces. Based on the PEGylated BST/BTS heterojunction, a novel thermoelectric therapy platform is developed through intravenous injection of BST/BTS and external cooling of the tumors. This thermoelectric strategy is also proved effective for combination cancer therapy with β‐elemene. Moreover, the combination of heterojunction and hydrogel is administrated on the wound after surgery, achieving efficient residual tumor treatment and antibacterial effects.

Glutathione‐Scavenging Nanoparticle‐Mediated PROTACs Delivery for Targeted Protein Degradation and Amplified Antitumor Effects

Abstract: PROteolysis TArgeting Chimeras (PROTACs) are an emerging class of promising therapeutic modalities that selectively degrade intracellular proteins of interest by hijacking the ubiquitin‐proteasome system. However, the lack of techniques to efficiently transport these degraders to targeted cells and consequently the potential toxicity of PROTACs limit their clinical applications. Here, a strategy of nanoengineered PROTACs, that is, Nano‐PROTACs, is reported, which improves the bioavailability of PROTACs and maximizes their capacity to therapeutically degrade intracellular oncogenic proteins for tumor therapy. The Nano‐PROTACs are developed by encapsulating PROTACs in glutathione (GSH)‐responsive poly(disulfide amide) polymeric (PDSA) nanoparticles and show that ARV@PDSA Nano‐PROTAC, nanoengineered BRD4 degrader ARV‐771, improves BRD4 protein degradation and decreases the downstream oncogene c‐Myc expression. Benefiting from the GSH‐scavenging ability to amply the c‐Myc‐related ferroptosis and cell cycle arrest, this ARV@PDSA Nano‐PROTACs strategy shows superior anti‐tumor efficacy with a low dose administration and good biocompatibility in vivo. The findings reveal the potential of the Nano‐PROTACs strategy to treat a broad range of diseases by dismantling associated pathogenic proteins.

Oral Hydrogel Microbeads-Mediated In Situ Synthesis of Selenoproteins for Regulating Intestinal Immunity and Microbiota.

Abstract: Selenoprotein plays a crucial role in immune cells and inflammatory regulation. However, as a protein drug that is easily denatured or degraded in the acidic environment of the stomach, efficient oral delivery of selenoprotein is a great challenge. Herein, we innovated an oral hydrogel microbeads-based biochemical strategy that can in situ synthesize selenoproteins, therefore bypassing the necessity and harsh conditions for oral protein delivery while effectively generating selenoproteins for therapeutic applications. The hydrogel microbeads were synthesized by coating hyaluronic acid-modified selenium nanoparticles with a protective shell of calcium alginate (SA) hydrogel. We tested this strategy in mice with inflammatory bowel disease (IBD), one of the most representative diseases related to intestinal immunity and microbiota. Our results revealed that hydrogel microbeads-mediated in situ synthesis of selenoproteins could prominently reduce proinflammatory cytokines secretion and mediate immune cells (e.g., reduce neutrophils and monocytes and increase immune regulatory T cells) to effectively relieve colitis-associated symptoms. This strategy was also able to regulate gut microbiota composition (increase probiotics abundance and suppress detrimental communities) to maintain intestinal homeostasis. Considering intestinal immunity and microbiota widely associated with cancers, infections, inflammations, etc., this in situ selenoprotein synthesis strategy might also be possibly applied to broadly tackle various diseases.

Living Leukocyte‐Based Drug Delivery Systems (Adv. Mater. 17/2023)

Abstract: Drug Delivery In article number 2207787, Can Yang Zhang, Wei Tao, and co-workers review the recent advances in living-leukocyte-mediated drug delivery. Due to the targeted response to the inflammatory environment, leukocytes (e.g., neutrophils, macrophages, and lymphocytes) have great potential as targeted carriers for drug delivery and are expected to bring breakthroughs in the precise treatment of cancer and inflammation-related diseases.

Nanomedicine for the Detection and Treatment of Ocular Bacterial Infections.

Abstract: Ocular bacterial infection is a prevalent cause of blindness worldwide, with substantial consequences for normal human life. Traditional treatments for ocular bacterial infections are ineffective, necessitating the development of novel techniques to enable accurate diagnosis, precise drug delivery, and effective treatment alternatives. With the rapid advancement of nanoscience and biomedicine, increasing emphasis has been placed on multifunctional nanosystems to overcome the challenges posed by ocular bacterial infections. Given the advantages of nanotechnology in the biomedical industry, it can be utilized to diagnose ocular bacterial infections, administer medications, and treat them. In this review, the recent advancements in nanosystems for the detection and treatment of ocular bacterial infections are discussed; this includes the latest application scenarios of nanomaterials for ocular bacterial infections, in addition to the impact of their essential characteristics on bioavailability, tissue permeability, and inflammatory microenvironment. Through an in-depth investigation into the effect of sophisticated ocular barriers, antibacterial drug formulations, and ocular immune metabolism on drug delivery systems, this review highlights the challenges faced by ophthalmic medicine and encourages basic research and future clinical transformation based on ophthalmic antibacterial nanomedicine. This article is protected by copyright. All rights reserved.

In situ Engineering of Tumor-Associated Macrophages via a Nanodrug-Delivering-Drug (β-Elemene@Stanene) Strategy for Enhanced Cancer Chemo-Immunotherapy.

Abstract: Tumor-associated macrophages (TAMs) play a critical role in the immunosuppressive solid tumor microenvironment, yet in situ engineering of TAMs for enhanced tumor immunotherapy remains a significant challenge in translational immune-oncology. Here, we report an innovative nanodrug-delivering-drug (STNSP@ELE) strategy that leverages two-dimensional (2D) stanene-based nanosheets (STNSP) and β-Elemene (ELE), a small-molecule anticancer drug, to overcome TAM-mediated immunosuppression and improve chemo-immunotherapy. Our results demonstrate that both STNSP and β-Elemene are capable of polarizing the tumor-supportive M2-like TAMs into tumor-suppressive M1-like phenotype, which acts with the ELE chemotherapeutic to booster anti-tumor responses. In vivo mouse studies demonstrate that STNSP@ELE treatment can reprogram the immunosuppressive TME by significantly increasing the intra-tumoral ratio of M1/M2-like TAMs, enhancing the population of CD4+ and CD8+ T lymphocytes and mature dendritic cells, and elevating the expression of immunostimulatory cytokines in B16F10 melanomas, thereby promoting a robust anti-tumor response. Our study not only demonstrates that the STNSP@ELE chemo-immunotherapeutic nanoplatform has immune-modulatory capabilities that can overcome TAM-mediated immunosuppression in solid tumors, but also highlights the promise of this nanodrug-delivering-drug strategy in developing other nano-immunotherapeutics and treating various types of immunosuppressive tumors.