A CTL-Inspired Killing System Using Ultralow-Dose Chemical-Drugs to Induce a Pyroptosis-Mediated Antitumor Immune Function.
Adv Mater
; 36(13): e2309839, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-38102944
ABSTRACT
A Cytotoxic T lymphocyte-inspired system capable of using ultralow-dose chemical drugs to manipulate cell death is needed to investigate the antitumor immunotherapy. Recent studies reveal pyroptosis promotes antitumor immune function. However, high-dose chemotherapy leads to cytokine release syndrome by pyroptosis. Therefore, pyroptosis-inducing ultralow-dose chemotherapy is potential in preclinical and clinical research, but its efficacy, safety, and the antitumor immune responses are not clear. Here, a near-infrared light controllable killing system (BIK system) is established by which ultralow-dose doxorubicin can be spatiotemporally transported to tumor cells and mediate efficient pyroptosis. This BIK system reduces total drug consumption to less than one-thirtieth the common dose in vitro. Moreover, this BIK system exhibited good tumor targeting and tumor penetration. This system is applied for pyroptosis-induced antitumor therapies, which shows less than ≈25 µg kg-1 doxorubicin is sufficient for tumor regression with negligible injuries to major organs. The antitumor immune function are proven to correlate with the impressive efficacy of pyroptosis-inducing ultralow-dose chemotherapy. This study provides new insights into the design of nanoassisted systems for activating the antitumor immunity by microstimulation; the application of the BIK system suggests that ultralow-dose chemotherapy is sufficient for inducing a robust pyroptosis-mediated antitumor immunity.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Piroptose
/
Neoplasias
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article