Phase-transition nanodroplets with immunomodulatory capabilities for potentiating mild magnetic hyperthermia to inhibit tumour proliferation and metastasis

Abstract

Background Magnetic hyperthermia (MHT)-mediated thermal ablation therapy has promising clinical applications in destroying primary tumours. However, traditional MHT still presents the challenges of damage to normal tissues adjacent to the treatment site and the destruction of tumour-associated antigens due to its high onset temperature (> 50 °C). In addition, local thermal ablation of tumours often exhibits limited therapeutic inhibition of tumour metastasis. Results To address the above defects, a hybrid nanosystem (SPIOs + RPPs) was constructed in which phase transition nanodroplets with immunomodulatory capabilities were used to potentiate supermagnetic iron oxide nanoparticle (SPIO)-mediated mild MHT (< 44 °C) and further inhibit tumour proliferation and metastasis. Magnetic-thermal sensitive phase-transition nanodroplets (RPPs) were fabricated from the immune adjuvant resiquimod (R848) and the phase transition agent perfluoropentane (PFP) encapsulated in a PLGA shell. Because of the cavitation effect of microbubbles produced by RPPs, the temperature threshold of MHT could be lowered from 50℃ to approximately 44℃ with a comparable effect, enhancing the release and exposure of damage-associated molecular patterns (DAMPs). The exposure of calreticulin (CRT) on the cell membrane increased by 72.39%, and the released high-mobility group B1 (HMGB1) increased by 45.84% in vivo. Moreover, the maturation rate of dendritic cells (DCs) increased from 4.17 to 61.33%, and the infiltration of cytotoxic T lymphocytes (CTLs) increased from 10.44 to 35.68%. Under the dual action of mild MHT and immune stimulation, contralateral and lung metastasis could be significantly inhibited after treatment with the hybrid nanosystem. Conclusion Our work provides a novel strategy for enhanced mild magnetic hyperthermia immunotherapy and ultrasound imaging with great clinical translation potential.

Theranostics: a multifaceted approach utilizing nano-biomaterials

“…The fabrication process included the creation of magnetic-thermal-sensitive phase-transition nanodroplets by encapsulating the immune adjuvant resiquimod (R848) and the phase-transition agent perfluoropentane inside a shell made of PLGA. This HNS therapy has been shown to considerably reduce contralateral and lung metastasis via the combined effects of moderate MHT and immune activation [ 32 ]. A recent study documented the efficacy of using a combination of MHT enhanced cancer immunotherapy and transcatheter arterial embolisation (TAE) as a viable approach for the treatment of hepatocellular carcinoma (HCC).…”

Nanoparticle-Mediated Synergistic Chemoimmunotherapy for Cancer Treatment

“…Ultimately, bioactive DAMP combined with R848 creates the highly immunogenic TME that activates both DC and CTL to combat tumor proliferation or metastasis. 212…”

New insights into nanosystems for non-small-cell lung cancer: diagnosis and treatment

“…The CLA-coated PTX-SIONs showed a drug loading efficiency of 98.5% and persistent site-specific release of PTX in vitro over 24 h, thus suggesting that the nanomedicine is a promising alternative for an effective drug delivery system targeted NSCLC. 145 Interestingly, Qin et al 146 designed a hybrid nanosystem (SIONs + RPPs) in which phase transition nanodroplets with immunomodulatory capabilities were used to potentiate SION-mediated mild magnetic hyperthermia (MHT, <44 °C) and further inhibit tumour proliferation and metastasis. Magnetic-thermal sensitive phase-transition nanodroplets (RPPs) were fabricated from the immune adjuvant resiquimod (R848) and the phase transition agent perfluoropentane (PFP) encapsulated in a PLGA shell.…”