Nanodrugs with intrinsic radioprotective exertion: Turning the double‐edged sword into a single‐edged knife

Zhu

et al. 2023

Adv Funct Materials

Self Cite

Tumor adaptation‐originated tumor tolerance that compensatory mechanisms (e.g., isocitrate dehydrogenase (IDH) mutation) jointly shape is the dominant obstacle of ROS therapy. Currently, targeting a single pathway fails to fundamentally reverse the complex milieu and diminish tumor adaptation. Herein, a multichannel sonocatalysis amplifier is engineered via one‐pot gas diffusion method to attenuate IDH1‐mutated cholangiocarcinoma plasticity and tolerance to ROS therapy, wherein triptolide and IR780 are co‐loaded in DSPE‐mPEG‐modified CaCO3 nanoparticles. Triptolide can blockade Nrf2 to cut off glutathione biosynthesis via blockading proteomic communication, and disrupt redox homeostasis to potentiate IR780‐mediated sonocatalytic ROS production. ROS‐induced mitochondria damages disrupt Ca2+ homeostasis and in turn aggravate ROS accumulation, which cooperates with sonocatalysis and Nrf2 blockade to reprogram mitochondrial energy and substance metabolism (e.g., adenosine triphosphatase and glutathione), hinder DNA self‐repair, and impair IDH1‐mutation‐asired tolerance. Systematic experiments support that these actions in such multichannel sonocatalysis amplifiers indeed disrupt Ca2+/redox homeostasis to disarm robust tumor plasticity and IDH1‐mutation‐induced tolerance to sonocatalysis therapy against IDH1‐mutated cholangiocarcinoma progression. Briefly, the sonocatalysis amplifiers pave a comprehensive avenue to reprogram tumor metabolism, target tumor vulnerability, and attenuate tumor plasticity against genomic instability‐raised treatment adaptation.

Section: In Vitro Mitochondria Damage Evaluationmentioning

confidence: 99%

Multichannel Sonocatalysis Amplifiers Target IDH1‐Mutated Tumor Plasticity and Attenuate Ros Tolerance to Repress Malignant Cholangiocarcinoma

Zhu

et al. 2023

Adv Funct Materials

Self Cite

“…Breast cancer is a malignancy that exhibits high metastatic potential. [8,10,[34][35][36][37][38][39][40][41][42][43][44][45] As CCs transfer to distant sites, therapeutic interventions become considerably complex and ineffective, and thus, early prevention is of great importance. We then evaluated the impact of biomimetic CSC/CC@DHAp NPs on the formation of early deterioration points.…”

Section: Early Metastasis Inhibition Evaluationmentioning

confidence: 99%

Targetedly Attenuating Cancer Stemness and Plasticity by Homologous Cancer Stem Cell‐Inherited Fusion Membrane Nanoeffectors against Cancer Metastasis

Dong,

Yang,

Wang

et al. 2023

Small Science

Self Cite

Cancer stem cells (CSCs) are highly related to initiate metastasis and drive tumor relapse/propagation, and the induced cancer stemness and plasticity render cancer intractable to various therapeutic approaches. To address them, a CSC membrane‐based fusion strategy is presented to target and attenuate cancer stemness and plasticity, and accordingly homogenous CSC‐inherited fusion membrane‐coated biomimetic nanoeffectors based on doxorubicin‐loaded hydroxyapatite nanoparticles are engineered. Such biomimetic nanoeffectors coated with fusion membrane consisting of CSCs and cancer cells can not only specifically target the solid breast tumor cells, but also target the latent CSCs. Systematic experiments validate that the constructed nanoeffectors disrupt energy metabolism, trigger lethal mitochondrial apoptosis, remarkably inhibit tumor proliferation, and downregulate the expressions of some target proteins associated with cancer stemness and metastasis to attenuate cancer stemness and the induced plasticity. Contributed by them, such nanoeffectors have been demonstrated to successfully hinder the progression of breast cancer, and decrease lung metastasis in two cancer metastasis mouse models. Such CSCs membrane‐based fusion membrane strategy provides a new candidate avenue rather than the currently dominant immune‐related pathway to repress cancer metastasis via targeting and attenuating cancer stemness.

“…It is well known that the most common adverse symptom of radiation therapy for cancer is gastrointestinal dysfunction, which can cause further damage to the body and terminate treatment 193 . However, gut microbial metabolites appear to be inextricably linked to radiation protection.…”

Section: Application Of Gut Microbes-mediated Metabolites In the Trea...mentioning

confidence: 99%

Cracking Brain Diseases from Gut Microbes-Mediated Metabolites for Precise Treatment

Gong¹,

Chen²,

Zhang³

et al. 2023

Int. J. Biol. Sci.

The gut-brain axis has been a subject of significant interest in recent years. Understanding the link between the gut and brain axis is crucial for the treatment of disorders. Here, the intricate components and unique relationship between gut microbiota-derived metabolites and the brain are explained in detail. Additionally, the association between gut microbiota-derived metabolites and the integrity of the blood-brain barrier and brain health is emphasized. Meanwhile, gut microbiota-derived metabolites with their recent applications, challenges and opportunities their pathways on different disease treatment are focus discussed. The prospective strategy of gut microbiota-derived metabolites potential applies to the brain disease treatments, such as Parkinson's disease and Alzheimer's disease, is proposed. This review provides a broad perspective on gut microbiota-derived metabolites characteristics facilitate understand the connection between gut and brain and pave the way for the development of a new medication delivery system for gut microbiota-derived metabolites.