An Alkaline Nanocage Continuously Activates Inflammasomes by Disrupting Multiorganelle Homeostasis for Efficient Pyroptosis.
ACS Appl Mater Interfaces
; 16(19): 24295-24307, 2024 May 15.
Article
in En
| MEDLINE
| ID: mdl-38697643
ABSTRACT
Pyroptosis has garnered increasing attention because of its ability to trigger robust antitumor immunity. Pyroptosis is initiated by the activation of inflammasomes, which are regulated by various organelles. The collaboration among organelles offers several protective mechanisms to prevent activation of the inflammasome, thereby limiting the induction of efficient pyroptosis. Herein, a multiorganelle homeostasis disruptor (denoted BLL) is constructed by encapsulating liposomes and bortezomib (BTZ) within a layered double hydroxide (LDH) nanocage to continuously activate inflammasomes for inducing efficient pyroptosis. In lysosomes, the negatively charged liposomes are released to recruit the NLRP3 inflammasomes through electrostatic interactions. ER stress is induced by BTZ to enhance the activation of the NLRP3 inflammasome. Meanwhile, the BLL nanocage exhibited H+-scavenging ability due to the weak alkalinity of LDH, thus disrupting the homeostasis of the lysosome and alleviating the degradation of the NLRP3 inflammasome by lysosomal-associated autophagy. Our results suggest that the BLL nanocage induces homeostatic imbalance in various organelles and efficient pyroptosis. We hope this work can provide new insights into the design of an efficient pyroptosis inducer by disrupting the homeostatic balance of multiple organelles and promote the development of novel antineoplastic platforms.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Inflammasomes
/
Pyroptosis
/
NLR Family, Pyrin Domain-Containing 3 Protein
/
Homeostasis
Limits:
Animals
/
Humans
Language:
En
Journal:
ACS Appl Mater Interfaces
/
ACS appl. mater. interfaces (Online)
/
ACS applied materials & interfaces (Online)
Journal subject:
BIOTECNOLOGIA
/
ENGENHARIA BIOMEDICA
Year:
2024
Document type:
Article
Country of publication:
Estados Unidos