In Situ Silver‐Based Electrochemical Oncolytic Bioreactor

Abstract

In this study, it is shown for the first time that a reduced graphene oxide (rGO) carrier has a 20‐fold higher catalysis rate than graphene oxide in Ag+ reduction. Based on this, a tumor microenvironment‐enabled in situ silver‐based electrochemical oncolytic bioreactor (SEOB) which switched Ag+ prodrugs into in situ therapeutic silver nanoparticles with and above 95% transition rate is constructed to inhibit the growths of various tumors. In this SEOB‐enabled intratumoral nanosynthetic medicine, intratumoral H2O2 and rGO act as the reductant and the catalyst, respectively. Chelation of aptamers to the SEOB‐unlocked prodrugs increases the production of silver nanoparticles in tumor cells, especially in the presence of Vitamin C, which is broken down in tumor cells to supply massive amounts of H2O2. Consequently, apoptosis and pyroptosis are induced to cooperatively contribute to the considerably‐elevated anti‐tumor effects on subcutaneous HepG2 and A549 tumors and orthotopic implanted HepG2 tumors in livers of nude mice. The specific aptamer targeting and intratumoral silver nanoparticle production guarantee excellent biosafety since it fails to elicit tissue damages in monkeys, which greatly increases the clinical translation potential of the SEOB system.

Breakthroughs in nanozyme-inspired application diversity

“…(4) To elevate the treatment efficiency, combined or synergistic therapy is usually encouraged. [139][140][141][142][143][144][145][146][147][148][149][150][151][152][153][154][155][156][157][158] Inspired by this, nanozymes can be integrated with immunotherapy, chemotherapy, and other ROS-highlighted therapy to magnify the treatment efficiency. This direction will also arouse more interests, propelling clinical translation especially when imparting these functions into one platform and realizing the all-in-one strategy.…”

Composite Hemostat Spray Seals Post-Surgical Blood Burst and Ameliorates Bacteria-Arised Inflammation for Expediting Wound Healing

“…To shed light on this principle, ROS level was surveyed since many reports have reported that Ag-mediated ROS production is beneficial for bacterial inhibition. ,, Herein, BBoxiProbeDHE probe solution, a cell membrane penetrating probe, was used since it could be specifically oxidized by ROS to produce red fluorescent substances whose intensity is proportional to the ROS level. Thereby, ROS positive cells were stained red in the whole nuclear region, and the red fluorescence in the nuclear region could be recorded by a fluorescence microscope.…”

“…27−34 Typically, Ag-based nanoparticles have been documented to produce ROS to inhibit bacteria expansion and repress tumor. 35,36 Regarding this, the in situ introduction of Ag in Ag-βZ is expected to not only kill bacteria and mitigate bacteria-arised infection but also promote proliferations of human umbilical vein endothelial cells (HUVECs) for accelerating wound healing (Figure 1). Intriguingly, a spraying method was employed to augment the applicability because it features easy-to-operate convenience.…”

“…Reactive oxygen species (ROS) are the double-sword; e.g., ROS has been documented to kill bacteria and promote differentiation and proliferation of cells, − which strictly matter the level of ROS. , Inspiringly, various methods have been developed to regulate ROS level via producing ROS or mitigating ROS. − Typically, Ag-based nanoparticles have been documented to produce ROS to inhibit bacteria expansion and repress tumor. , Regarding this, the in situ introduction of Ag in Ag-βZ is expected to not only kill bacteria and mitigate bacteria-arised infection but also promote proliferations of human umbilical vein endothelial cells (HUVECs) for accelerating wound healing (Figure ). Intriguingly, a spraying method was employed to augment the applicability because it features easy-to-operate convenience. ,, The components in such composite Ag-βZ-F/T hemostats are authorized to be biosafe since they have been approved in clinics, determining that the composite zeolite-based hemostats hold high potential in clinical translation.…”

Bioorthogonal Disruption of Pyroptosis Checkpoint for High-Efficiency Pyroptosis Cancer Therapy

“…Pyroptosis is an emerging programmed cell death with the characteristics of cell membrane rupture, continuous cell swelling, and leakage of intracellular proinflammatory mediators. − During the pyroptosis process, the formation of inflammasomes activates the caspase 1 and pro-inflammatory cytokines (IL-1β and IL-18), and caspase-1 can cleave gasdermin D to release the N-terminal domain (GSDMD-N) which executes pyroptosis via its pore-forming activity. ,− To date, pyroptosis has attracted widespread concern in cancer therapy, and a variety of nanomaterials have been developed to elicit pyroptosis by photodynamic therapy, chemodynamic therapy, and so on. − However, pyroptosis still inevitably suffers from setbacks arising from the intrinsic adaptive survival mechanism and treatment resistance of cancer cells. ,,,, Notably, recent studies have reported that autophagy may act as a checkpoint to negatively regulate pyroptosis, thus resulting in therapeutic resistance. − …”