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- Title
A Smart Responsive Nanotheranostic System for MRI of Tumor Response to Immunotherapy and Enhanced Synergism of Thermo‐Immunotherapy.
- Authors
Li, Minghua; Lin, Chao; Shen, Aijun; Ma, Xiaolong; Ni, Jiong; Wu, Jiaqi; Wang, Wei; Wang, Peijun; Gao, Xiaolong
- Abstract
The challenges associated with the assessment of immune checkpoint inhibitor (ICI) therapy and low immunotherapy response observed in patients with poorly immunogenic tumors are addressed. A smart‐responsive nanoprobe MZF@Gd is synthetized based on magnetic resonance tuning (MRET). The nanoprobe is designed to be targeted and cleaved by granzyme B, a marker of cytotoxic T‐cell activation. MZF@Gd consisted of superparamagnetic Mn‐ and Zn‐doped ferrite magnetic nanoparticles (MZF‐MNPs) with a magnetocaloric effect and a paramagnetic contrast agent gadolinium‐diethylenetriamine penta‐acetic acid (Gd‐DTPA). These components are connected by the granzyme B substrate peptides. The activation of the T1WI signal through MRET, following the cleavage of the probe by granzyme B, enabled the accurate evaluation of the ICI therapeutic effect. Subsequently, an active‐targeting magnetothermally responsive nanotheranostic agent FA‐P(MZF@Gd/JQ1) is fabricated. This agent incorporated the MRET probe MZF@Gd, JQ‐1 (an inhibitor of PD‐L1), the thermosensitive copolymer PCL‐b‐P(MEO2MA‐co‐OEGMA), and folic acid on the surface. Nanotheranostic agents killed tumor cells through magnetocaloric effects, stimulated antitumor immunity, and regulated the drug release, thereby achieving a synergistic effect between hyperthermia and immunotherapy. Moreover, MZF@Gd released from the agent sensitively detected the presence of granzyme B at the tumor site, thereby enabling an effective assessment of therapeutic efficacy.
- Subjects
IMMUNE checkpoint inhibitors; IMMUNOTHERAPY; MAGNETOCALORIC effects; MAGNETIC resonance; CYTOTOXIC T cells; MAGNETIC nanoparticles; T cells; MOLECULAR probes
- Publication
Advanced Functional Materials, 2024, Vol 34, Issue 23, p1
- ISSN
1616-301X
- Publication type
Article
- DOI
10.1002/adfm.202315171