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Tumor-killing nanoreactors fueled by tumor debris can enhance radiofrequency ablation therapy and boost antitumor immune responses
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Tumor-killing nanoreactors fueled by tumor debris can enhance radiofrequency ablation therapy and boost antitumor immune responses
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Journal Article
Tumor-killing nanoreactors fueled by tumor debris can enhance radiofrequency ablation therapy and boost antitumor immune responses
2021
Overview
Radiofrequency ablation (RFA) is clinically adopted to destruct solid tumors, but is often incapable of completely ablating large tumors and those with multiple metastatic sites. Here we develop a CaCO
3
-assisted double emulsion method to encapsulate lipoxidase and hemin with poly(lactic-co-glycolic acid) (PLGA) to enhance RFA. We show the HLCaP nanoreactors (NRs) with pH-dependent catalytic capacity can continuously produce cytotoxic lipid radicals via the lipid peroxidation chain reaction using cancer cell debris as the fuel. Upon being fixed inside the residual tumors post RFA, HLCaP NRs exhibit a suppression effect on residual tumors in mice and rabbits by triggering ferroptosis. Moreover, treatment with HLCaP NRs post RFA can prime antitumor immunity to effectively suppress the growth of both residual and metastatic tumors, also in combination with immune checkpoint blockade. This work highlights that tumor-debris-fueled nanoreactors can benefit RFA by inhibiting tumor recurrence and preventing tumor metastasis.
Radiofrequency ablation (RFA) is a minimally invasive tumor ablation method, however incomplete ablation and the induction of an immunosuppressive microenvironment limit its efficacy in the clinic. Here the authors design a pH-responsive lipoxidase-loaded nanoreactor, that by triggering ferroptosis and anti-tumor immunity, amplify the therapeutic benefits of RFA in preclinical models.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 64/60
/ 82/51
/ Ablation
/ Adjuvants, Immunologic - chemistry
/ Adjuvants, Immunologic - pharmacology
/ Adjuvants, Immunologic - therapeutic use
/ Animals
/ Calcium Carbonate - chemistry
/ Calcium Carbonate - therapeutic use
/ Debris
/ Detritus
/ Hemin
/ Humanities and Social Sciences
/ Humans
/ Immune Checkpoint Inhibitors - therapeutic use
/ Immunity
/ Immunogenic Cell Death - drug effects
/ Lipid Peroxidation - drug effects
/ Lipids
/ Lipoxygenase - therapeutic use
/ Mice
/ Polylactic Acid-Polyglycolic Acid Copolymer - chemistry
/ Polylactic Acid-Polyglycolic Acid Copolymer - therapeutic use
/ Rabbits
/ Science
/ Tumors
