The past decades have witnessed hyperthermia therapy (HTT) as an emerging strategy against malignant tumors. Nanomaterial-based photothermal therapy (PTT) and magnetic hyperthermia (MHT), as highly effective and noninvasive treatment models, offer advantages over other strategies in the treatment of different types of tumors. However, both PTT and MHT cannot completely cure cancer due to recurrence and distal metastasis. In recent years, cancer immunotherapy has attracted widespread attention owing to its capability to activate the body's own natural defense to identify, attack, and eradicate cancer cells. Significant efforts have been devoted to studying the activated immune responses caused by hyperthermia-ablated tumors. In this article, the synergistic mechanism of HTT in immunotherapy, including immunogenic cell death and reversal of the immunosuppressive tumor microenvironment is discussed. The reports of the combination of HTT or HTT-based multimodal therapy with immunotherapy, including immunoadjuvant exploitation, immune checkpoint blockade therapy, and adoptive cellular immunotherapy are summarized. As highlighted, these strategies could achieve synergistically enhanced therapeutic outcomes against both primary tumors and metastatic lesions, prevent cancer recurrence, and prolong the survival period. Finally, current challenges and prospective developments in HTT-synergized immunotherapy are also reviewed.

Recent Advances in Hyperthermia Therapy-Based Synergistic Immunotherapy.

Exogenous stimulation catalytic therapy has received enormous attention as it holds great promise to address global medical issues. However, the therapeutic effect of catalytic therapy is seriously restricted by the fast charge recombination and the limited utilization of exogenous stimulation by catalysts. In the past few decades, many strategies have been developed to overcome the above serious drawbacks, among which heterojunctions are the most widely used and promising strategy. This review attempts to summarize the recent progress in the rational design and fabrication of heterojunction nanomedicine, such as semiconductor–semiconductor heterojunctions (including type I, type II, type III, PN, and Z–scheme junctions) and semiconductor–metal heterojunctions (including Schottky, Ohmic, and localized surface plasmon resonance–mediated junctions). The catalytic mechanisms and properties of the above junction systems are also discussed in relation to biomedical applications, especially cancer treatment and sterilization. This review concludes with a summary of the challenges and some perspectives on future directions in this exciting and still evolving field of research.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/advs.202105747

Heterojunction Nanomedicine

CuS-modified hollow mesoporous organosilica nanoparticles (HMON@CuS) have been preferred as non-invasive treatment for cancer, as near infrared (NIR)-induced photo-thermal effect (PTT) and/or photo-dynamic effect (PDT) could increase cancer cells’ apoptosis. However, the certain role of HMON@CuS-produced-PTT&PDT inducing gastric cancer (GC) cells’ mitochondrial damage, remained unclear. Moreover, theranostic efficiency of HMON@CuS might be well improved by applying multi-modal imaging, which could offer an optimal therapeutic region and time window. Herein, new nanotheranostics agents were reported by Gd doped HMON decorated by CuS nanocrystals (called HMON@CuS/Gd). HMON@CuS/Gd exhibited appropriate size distribution, good biocompatibility, l-Glutathione (GSH) responsive degradable properties, high photo-thermal conversion efficiency (82.4%) and a simultaneous reactive oxygen species (ROS) generation effect. Meanwhile, HMON@CuS/Gd could efficiently enter GC cells, induce combined mild PTT (43–45 °C) and PDT under mild NIR power density (0.8 W/cm2). Surprisingly, it was found that PTT might not be the only factor of cell apoptosis, as ROS induced by PDT also seemed playing an essential role. The NIR-induced ROS could attack mitochondrial transmembrane potentials (MTPs), then promote mitochondrial reactive oxygen species (mitoROS) production. Meanwhile, mitochondrial damage dramatically changed the expression of anti-apoptotic protein (Bcl-2) and pro-apoptotic protein (Bax). Since that, mitochondrial permeability transition pore (mPTP) was opened, followed by inducing more cytochrome c (Cyto C) releasing from mitochondria into cytosol, and finally activated caspase-9/caspase-3-depended cell apoptosis pathway. Our in vivo data also showed that HMON@CuS/Gd exhibited good fluorescence (FL) imaging (wrapping fluorescent agent), enhanced T1 imaging under magnetic resonance imaging (MRI) and infrared thermal (IRT) imaging capacities. Guided by FL/MRI/IRT trimodal imaging, HMON@CuS/Gd could selectively cause mild photo-therapy at cancer region, efficiently inhibit the growth of GC cells without evident systemic toxicity in vivo. HMON@CuS/Gd could serve as a promising multifunctional nanotheranostic platform and as a cancer photo-therapy agent through inducing mitochondrial dysfunction on GC.

/pdf/biodegradable-hollow-mesoporous-organosilica-2wz9l0nrgu.pdf

Biodegradable hollow mesoporous organosilica nanotheranostics (HMON) for multi-mode imaging and mild photo-therapeutic-induced mitochondrial damage on gastric cancer

Functional colloidal nanoparticles capable of converting between various energy types are finding an increasing number of applications. One of the relevant examples concerns light-to-heat-converting colloidal nanoparticles that may be useful for localized photothermal therapy of cancers. Unfortunately, quantitative comparison and ranking of nanoheaters are not straightforward as materials of different compositions and structures have different photophysical and chemical properties and may interact differently with the biological environment. In terms of photophysical properties, the most relevant information to rank these nanoheaters is the light-to-heat conversion efficiency, which, along with information on the absorption capacity of the material, can be used to directly compare materials. In this work, we evaluate the light-to-heat conversion properties of 17 different nanoheaters belonging to different groups (plasmonic, semiconductor, lanthanide-doped nanocrystals, carbon nanocrystals, and metal oxides). We conclude that the light-to-heat conversion efficiency alone is not meaningful enough as many materials have similar conversion efficiencies—in the range of 80–99%—while they significantly differ in their extinction coefficient. We therefore constructed their qualitative ranking based on the external conversion efficiency, which takes into account the conventionally defined light-to-heat conversion efficiency and its absorption capacity. This ranking demonstrated the differences between the samples more meaningfully. Among the studied systems, the top-ranking materials were black porous silicon and CuS nanocrystals. These results allow us to select the most favorable materials for photo-based theranostics and set a new standard in the characterization of nanoheaters.

Quantitative Comparison of the Light-to-Heat Conversion Efficiency in Nanomaterials Suitable for Photothermal Therapy

Early and accurate diagnosis of pathogenic bacteria is essential to prevent further infection from spreading and multiplying. Herein, an aptamer (Apt) biosensor based on Fe3O4@Au nanocomposites (NCs) has been proposed for capture, surface-enhanced Raman scattering (SERS) detection, and photothermal therapy (PTT) of S. aureus. Fe3O4@Au NCs become SERS substrate and photothermal agent due to superior surface plasmon properties and photothermal ability, while the aptamer immobilized on surface of Fe3O4@Au NCs acts as a capture agent. The detection limit of optimized Fe3O4@Au-Apt aptasensor for S. aureus is 25 cfu/mL, and cell capture efficiency (CCE) is as high as 68%. Moreover, our Fe3O4@Au-Apt NCs have high photothermal conversion efficiency of 39.28%, which have been proven as an excellent photothermal agent. As verified by experiments, Fe3O4@Au-Apt aptasensor is not only a promising tool to detect and photothermally inactivated S. aureus in milk samples, but also exhibits negligible cytotoxicity and good biocompatibility. This work shows a promising multifunctional nano-platform, which has great potential in specific recognition, sensitive SERS detection and PTT of S. aureus. 

Aptamer-conjugated magnetic Fe3O4@Au core-shell multifunctional nanoprobe: A three-in-one aptasensor for selective capture, sensitive SERS detection and efficient near-infrared light triggered photothermal therapy of Staphylococcus aureus

Enhanced photoconversion performance of NdVO4/Au nanocrystals for photothermal/photoacoustic imaging guided and near infrared light-triggered anticancer phototherapy

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Enhanced photoconversion performance of NdVO4/Au nanocrystals for photothermal/photoacoustic imaging guided and near infrared light-triggered anticancer phototherapy