Magnetism-mediated targeting hyperthermia-immunotherapy in “cold” tumor with CSF1R inhibitor

Abstract

Background: Immunotherapy has profoundly changed the landscape of cancer management and represented the most significant breakthrough. Yet, it is a formidable challenge that the majority of cancers - the so-called “cold” tumors - poorly respond to immunotherapy. To find a general immunoregulatory modality that can be applied to a broad spectrum of cancers is an urgent need. Methods: Magnetic hyperthermia (MHT) possesses promise in cancer therapy. We develop a safe and effective therapeutic strategy by using magnetism-mediated targeting MHT-immunotherapy in “cold” colon cancer. A magnetic liposomal system modified with cell-penetrating TAT peptide was developed for targeted delivery of a CSF1R inhibitor (BLZ945), which can block the CSF1-CSF1R pathway and reduce M2 macrophages. The targeted delivery strategy is characterized by its magnetic navigation and TAT-promoting intratumoral penetration. Results: The liposomes (termed TAT-BLZmlips) can induce ICD and cause excessive CRT exposure on the cell surface, which transmits an “eat-me” signal to DCs to elicit immunity. The combination of MHT and BLZ945 can repolarize M2 macrophages in the tumor microenvironment to relieve immunosuppression, normalize the tumor blood vessels, and promote T-lymphocyte infiltration. The antitumor effector CD8 + T cells were increased after treatment. Conclusion: This work demonstrated that TAT-BLZmlips with magnetic navigation and MHT can remodel tumor microenvironment and activate immune responses and memory, thus inhibiting tumor growth and recurrence.

Ferromagnetic Cytocompatible Glass‐Ceramic Porous Microspheres for Magnetic Hyperthermia Applications

“…[10] The main benefit of MHT relates to its ability to treat site-specific cancer whilst avoiding hazardous systemic effects. [11] Furthermore, MHT is minimally invasive (i.e., delivered intratumorally or intravenously by injection), with mild side effects compared to radiotherapy or chemotherapy, [10] and shows synergistic effects with many cancer treatments, e.g., brachytherapy, [12] drug-delivery, [13] immunotherapy, [14] and gene therapy. [15] Highly porous, ferromagnetic glass-ceramic P40-Fe 3 O 4 microspheres (125-212 µm) with enhanced cytocompatibility have been manufactured for the first time via a facile, rapid, single-stage flame spheroidization process.…”

Minimally invasive nanomedicine: nanotechnology in photo-/ultrasound-/radiation-/magnetism-mediated therapy and imaging

“…187 For example, the magnetic liposome constructed by Fang et al showed significant magnetic targeting ability and could be effectively accumulated in tumor sites under the action of an external magnetic field. 188 Meanwhile, as a stimulus with no tissue depth limitation, a magnetic field can also precisely regulate drug release from deep diseases without causing significant side effects to surrounding healthy tissues. For instance, a transferrin-conjugated doxorubicin-encapsulated magnetic nanoplatform could effectively release the drug in brain tumors under an external magnetic field.…”

Development of functional nanomedicines for tumor associated macrophages-focused cancer immunotherapy

“…For external stimuli, hyperthermia can be utilized as a physical stimulus for antitumor therapeutic response of NPs. There was a study about magnetic hyperthermia, namely that a liposome loaded with superparamagnetic NPs and CSF1R inhibitor BLZ945 were constructed for antitumor immune response under magnetic hyperthermia responses 138 . Photo, identified as a common physical responsiveness, are usually applied for some inorganic NPs with optical/electronic properties, including AuNRs/NPs, Fe 3 O 4 NPs, BP NPs, etc.…”