Abstract
BackgroundComprehensive antitumor therapy through integrated multimodal means has drawn increasing attention owing to its high efficiency and metastasis suppression.ResultsWe describe a synergistic triple protocol combining photothermal and sonodynamic therapy (PTT and SDT), together with immune checkpoint blockade for the inhibition of breast cancer growth and metastases in the 4T1 mouse model. PTT and SDT are synergistically augmented by a novel multimodal imaging nanoprobe integrated with cancer cell membrane-biomimetic nanoparticles (CHINPs) loaded with superparamagnetic iron oxide (SPIO) and hematoporphyrin monomethyl ether (HMME). CHINPs exhibit excellent homologous tumor targeting, and are sequentially triggered by ultrasound and near infrared (NIR) light under the guidance of magnetic resonance, photoacoustic and photothermal imaging, leading to complete in situ tumor eradication and systemic anti-tumor immune activation. Further combination of this approach with immune checkpoint blockade therapy is shown to suppress tumor metastasis.ConclusionThis work provides proof-of-principle for triple therapy using multimodal imaging-guided PTT/SDT based on biomimetic nanoprobes in combination with immunotherapy to eliminate tumors.Graphical
Highlights
Comprehensive antitumor therapy through integrated multimodal means has drawn increasing attention owing to its high efficiency and metastasis suppression
The average size of CHINPs increased to 228.07 ± 6.21 nm and the zeta-potential decreased to − 19.27 ± 0.55 mV, indicating that the nanoparticles had been successfully coated with Cancer cell membranes (CCMs) (Fig. 1A, B)
Under transmission electron microscopy (TEM) (Fig. 1C, D), CHINPs appeared as a typical "shell core" like spherical structure with 9 nm CCMs coating on the surface, which is consistent with previous reports [52, 56, 58, 59]
Summary
Comprehensive antitumor therapy through integrated multimodal means has drawn increasing attention owing to its high efficiency and metastasis suppression. Combined antitumor therapy strategies exploring different therapeutic approaches and/or related mechanisms of action have great application prospects. Showing both effectiveness and low toxicity, numerous studies have highlighted the potential of comprehensive antitumor therapy with multifunctional nanoplatforms to solve many current limitations of cancer treatment [2,3,4,5]. Sonodynamic therapy (SDT) is a noninvasive therapeutic strategy for the treatment of deep tumors. The severe hypoxia in the solid tumor microenvironment (TME) and oxygen consumption during SDT greatly hinders the ROS production, which leads to dramatic decline of SDT therapeutic efficiency [21,22,23]
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