FeP-Based Nanotheranostic Platform for Enhanced Phototherapy/Ferroptosis/Chemodynamic Therapy.

Ferroptosis is an iron-dependent and lipid peroxides (LPO)-overloaded programmed damage cell death, induced by glutathione (GSH) depletion and glutathione peroxide 4 (GPX4) inactivation. However, the inadequacy of endogenous iron and reactive oxygen species (ROS) restricts the efficacy of ferroptosis. To overcome this obstacle, a near-infrared photo-responsive FeP@PEG NPs is fabricated. Exogenous iron pool can enhance the effect of ferroptosis via the depletion of GSH and further regulate GPX4 inactivation. Generation of ·OH derived from the Fenton reaction is proved by increased accumulation of lipid peroxides. The heat generated by photothermal therapy and ROS generated by photodynamic therapy can enhance cell apoptosis under near-infrared (NIR-808 nm) irradiation, as evidenced by mitochondrial dysfunction and further accumulation of lipid peroxide content. FeP@PEG NPs can significantly inhibit the growth of several types of cancer cells in vitro and in vivo, which is validated by theoretical and experimental results. Meanwhile, FeP@PEG NPs show excellent T2-weighted magnetic resonance imaging (MRI) property. In summary, the FeP-based nanotheranostic platform for enhanced phototherapy/ferroptosis/chemodynamic therapy provides a reliable opportunity for clinical cancer theranostics.

Low-work-function LaB6 for realizing photodynamic-enhanced photothermal therapy.

There is great potential for photodynamic therapy (PDT)-enhanced photothermal therapy (PTT) to be used for tumor therapy, especially for the single material-mediated process that could greatly simplify the experimental arrangements. This study presents a new cancer phototherapeutic agent consisting of low-work-function lanthanum hexaboride particles, which are excellent light absorbers in the near-infrared (NIR) region. The photothermal effect and reactive oxygen species production were realized by LaB6 under NIR light irradiation. Theoretical calculations based on density functional theory confirmed that the strong NIR light absorption by LaB6 was attributed to the local plasmonic resonance effect and the excellent photodynamic effect derived from the low work function. In vivo treatment of HepG2 tumor-bearing mice revealed that LaB6-mediated phototherapy resulted in excellent tumor inhibitory effects, and no adverse effects on mice were observed. These results indicate that LaB6 is a promising phototherapeutic agent for cancer synergetic phototherapy.

Phototherapy together with it triggered immunological response for Anti-HPV treatment of oropharyngeal cancer: Removing tumor and pathogenic virus simultaneously.

Oropharyngeal squamous cell carcinoma (OPSCC) is one of most common cancers that often brings lots of inconvenience to the patient in swallowing and phonation even after the operation. Moreover, OPSCC is typically as nodal metastases and high recurrence rate due to the high-risk human papillomavirus (HPV) infection for 90% of patients. Obviously, completely curing OPSCC requires simultaneous removal of solid tumor and related pathogenic virus, which is very indispensable but never be realized by any kind of clinical therapy up to now. In this work, we selected the ZrC nanoparticles as difunctional photoactive substance for synchronous generation of hyperthermia and reactive oxygen species (ROS) under NIR excitation. The resultant synergistic photothermal and photodynamic treatment outcome contributed to an excellent anti-tumor effect. The phototherapy of this work was found not only to be able to damage cancer cells directly, but also could trigger the host immunity for further tumor removal and desirable HPV inactivation. An immunologic mechanism of this work was reasonable proposed by monitoring level of shock protein (HSP), calreticulin (CRT), T lymphocytes and dendritic cells (DCs) and immune check point of B7H3, B7H4 and PD-L1 post phototherapy. It was found that tumor-associated antigens of CRT ("eat-me" signal), HSPs and cell debris were released as cancer cell damage, and then the adaptive immune system and the congenital immunity were triggered to activate DCs maturity, antigen presentation to T cells, proliferation of CD4+ and CD8+ T cells, recruiting macrophages and NK cells and so forth immune responses. Being the first example of using phototherapy for virus-related cancer study, this work opens the door for photo-immunotherapy.

Cell-cargo mediated ZrN nanoparticle for the synergetic phototherapy on both of mice and rabbits.

Realization of phototherapy on the big animal modal with orthotopic tumor is of considerable significance in view of its great clinical relevance to the human deep tumor treatment. Herein, near infrared (NIR)-active ZrN nanoparticles were chosen for both of photothermal and photodynamic purposes to achieve the synergetic phototherapy on mice with subcutaneous tumor and even rabbits bearing with orthotopic tumor. Broad and strong photoabsorption, photosensitive ROS generation and photothermal effect of ZrN nanoparticles together made it to be ideal candidate for the effective tumor photoablation. Meanwhile, cell-cargo of macrophage enables targeted delivery of ZrN nanoparticles without influence on its photophysical properties. Resultantly, macrophage loaded ZrN could efficiently mediate synergetic phototherapeutic outcome as proved by complete removal of solid tumor from mice and rabbits. In this work, we also introduced B-mode ultrasonography and contrast-enhanced ultrasound technique for monitoring the evolution process of deep orthotopic tumor on rabbits post-treatment and confirmed the pathological changes of vascular degeneration and liquefaction necrosis post phototherapy.

Targeted photothermal therapy of mice and rabbits realized by macrophage-loaded tungsten carbide.

Although great advances have been made in photothermal therapy, the efforts hitherto have mainly achieved antitumor effects in mice with a subcutaneous tumor model, which is less clinically relevant. Therefore, it is very urgent to make further progress in investigating the possibility of larger animal models with orthotopically xenografted tumors for further clinical trials. Herein, macrophage-loaded tungsten carbide has been employed for the photothermal ablation of orthotopic breast tumors in rabbits in a targetable way. Tungsten carbide as an excellent photoactive material can induce on-site hyperthermia and even reactive oxygen species for tumor destruction; meanwhile, the macrophage is a biocarrier that behaves as a "Trojan horse" for tumor targeting. Both experimental results and theoretical simulations verified the broadband photoabsorption of WC. The WC loaded in the macrophages readily maintains the photothermal and photodynamic effects of the bare WC, while its accumulation at the tumor site is nearly 10 times that of bare WC. As such, the complete removal of solid tumors in rabbits was confirmed with the aid of B-mode ultrasound and contrast-enhanced ultrasound surveillance. Apparently, this work advances photothermal therapy one step further to large animal models with orthotopic tumors.

A near-infrared responsive germanium complex of Ge/GeO2 for targeted tumor phototherapy.

The development of photoactive nanomaterials with high biocompatibility for targeted tumor phototherapy is of great significance for antitumor applications; this study presents a novel phototherapeutic agent, the Ge/GeO2 complex, which shows broad photoabsorption in the near infrared (NIR) region. As a result, it can synchronously produce reactive oxygen species (ROS) and heat under NIR irradiation. After being loaded onto macrophages, Ge/GeO2 could be delivered to tumors in a targeted fashion. Combining the abovementioned merits together, macrophage-loaded Ge/GeO2 realized in vivo synergetic photothermal and photodynamic outcomes to completely remove solid tumors in mice via intravenous administration. In this study, B-ultrasonography was also employed to monitor the tumor evolution after phototherapy, revealing a sequential process of tumor necrosis, liquefaction/softening, and finally disappearance. In addition, Ge/GeO2 proposed in this study shows negligible cytotoxicity and hematotoxicity, especially after being loaded onto macrophages.

The theranostic nanoagent Mo2C for multi-modal imaging-guided cancer synergistic phototherapy.

Multifunctional theranostic platforms, especially single component-based platforms, enable both cancer treatment and real-time imaging as well as enhance the efficiency of treatment. In this study, 50 nm Mo2C nanospheres were explored as a "one-for-all" theranostic agent. The light-harvesting of Mo2C covered the entire near infrared region, and NIR irradiation concurrently triggered hyperthermia and reactive oxygen species (ROS) production; thus, synergistic outcomes of photothermal and photodynamic therapy could be realized. Both in vitro and in vivo experiments have confirmed the superiority of the synergistic phototherapy in killing cancer cells and removing solid tumors; moreover, Mo2C proposed herein has been proven to be applicable as a photoacoustic imaging and CT imaging contrast agent for in vivo tumor depiction; furthermore, Mo2C demonstrates excellent biocompatibility, showing minimal hematotoxicity and tissue toxicity. A theoretical simulation performed by density functional theory revealed that the metallic character and the interband/intraband transition of Mo2C accounted for its broad photoabsorption. The antitumor mechanism of Mo2C was investigated on a solid tumor by B-mode ultrasonography (US) and magnetic resonance imaging (MRI), revealing a typical liquefactive necrosis process; hence, herein, the dual-imaging guided phototherapy was efficiently mediated by Mo2C.

SnxWO3 as a theranostic platform for realizing multi-imaging-guided photothermal/photodynamic combination therapy.

Precise oncotherapy requires effective cancer treatments that are guided by clinical imaging techniques. One of the most representative cases is multi-imaging-guided phototherapy. This study presents a novel multifunctional theranostic agent of SnxWO3 tungsten bronze, which is an excellent light absorber in the near infrared (NIR) range. Theoretical calculations based on density functional theory confirm that the insertion of donor Sn atoms into orthorhombic WO3 gives rise to the broadband visible-NIR absorption. Accordingly, both the photothermal effect and reactive oxygen species (ROS) production could be realized under NIR light irradiation by SnxWO3 tungsten bronze nanocrystals, thereby triggering the potent in vivo photothermal and photodynamic synergistic therapy. Meanwhile, modified SnxWO3 tungsten bronze has the functions of photoacoustic imaging (PAI), X-ray computed tomography (CT) imaging and near-infrared fluorescence (NIRF) imaging for tumor detection as well. Finally, for investigating the antitumor mechanism of in vivo solid tumors, clinical imaging modalities of B-mode ultrasonography (US) and magnetic resonance imaging (MRI) are employed to monitor the tumor evolution process after the photo-treatment, verifying a typically liquefactive necrosis process. These results indicate that the SnxWO3 tungsten bronze nanostructure is a promising theranostic agent for imaging-guided cancer therapy.

Surface-engineered vanadium nitride nanosheets for an imaging-guided photothermal/photodynamic platform of cancer treatment.

Of the many strategies for precise tumor treatment, near-infrared (NIR) light-activated "one-for-all" theranostic modality with real-time diagnosis and therapy has attracted extensive attention from researchers. Herein, a brand-new theranostic nanoplatform was established on versatile vanadium nitride (VN) nanosheets, which show significant NIR optical absorption, and resultant photothermal effect and reactive oxygen species activity under NIR excitation, thereby realizing the synergistic action of photothermal/photodynamic co-therapy. As expected, systematic in vitro and in vivo antitumor evaluations demonstrated efficient cancer cell killing and solid tumor removal without recurrence. Meanwhile, the surface modification of VN nanosheets with poly(allylamine hydrochloride) and bovine serum albumin enhanced the biocompatibility of VN and made it more suitable for in vivo delivery. Moreover, VN has been ascertained as a potential photoacoustic imaging contrast for in vivo tumor depiction. Thus, this work highlights the potential of VN nanosheets as a single-component theranostic nanoplatform.

Multifunctional Theranostic Agent of Cu2(OH)PO4 Quantum Dots for Photoacoustic Image-Guided Photothermal/Photodynamic Combination Cancer Therapy.

Image-guided phototherapy is considered to be a prospective technique for cancer treatment because it can provide both oncotherapy and bioimaging, thus achieving an optimized therapeutic efficacy and higher treatment accuracy. Compared to complicated systems with multiple components, using a single material for this multifunctional purpose is preferable. In this work, we strategically fabricated poly(acrylic acid)- (PAA-) coated Cu2(OH)PO4 quantum dots [denoted as Cu2(OH)PO4@PAA QDs], which exhibit a strong near-infrared photoabsorption ability. As a result, an excellent photothermal conversion ability and the photoactivated formation of reactive oxygen species could be realized upon NIR irradiation, concurrently meeting the basic requirements for photothermal and photodynamic therapies. Moreover, phototherapeutic investigations on both cervical cancer cells in vitro and solid tumors of an in vivo mice model illustrated the effective antitumor effects of Cu2(OH)PO4@PAA upon 1064-nm laser irradiation, with no detectable lesions in major organs during treatment. Meanwhile, Cu2(OH)PO4@PAA is also an exogenous contrast for photoacoustic tomography (PAT) imaging to depict tumors under NIR irradiation. In brief, the Cu2(OH)PO4@PAA QDs prepared in this work are expected to serve as a multifunctional theranostic platform.

MoO3-x quantum dots for photoacoustic imaging guided photothermal/photodynamic cancer treatment.

A theranostic system of image-guided phototherapy is considered as a potential technique for cancer treatment because of the ability to integrate diagnostics and therapies together, thus enhancing accuracy and visualization during the treatment. In this work, we realized photoacoustic (PA) imaging-guided photothermal (PT)/photodynamic (PD) combined cancer treatment just via a single material, MoO3-x quantum dots (QDs). Due to their strong NIR harvesting ability, MoO3-x QDs can convert incident light into hyperthermia and sensitize the formation of singlet oxygen synchronously as evidenced by in vitro assay, hence, they can behave as both PT and PD agents effectively and act as a "dual-punch" to cancer cells. In a further study, elimination of solid tumors from HeLa-tumor bearing mice could be achieved in a MoO3-x QD mediated phototherapeutic group without obvious lesions to the major organs. In addition, the desired PT effect also makes MoO3-x QDs an exogenous PA contrast agent for in vivo live-imaging to depict tumors. Compared with previously reported theranostic systems that put several components into one system, our multifunctional agent of MoO3-x QDs is exempt from unpredictable mutual interference between components and ease of leakage of virtual components from the composited system.

Csx WO3 Nanorods Coated with Polyelectrolyte Multilayers as a Multifunctional Nanomaterial for Bimodal Imaging-Guided Photothermal/Photodynamic Cancer Treatment.

Csx WO3 nanorods coated with polyelectrolyte multilayers are developed as "four-in-one" multifunctional nanomaterials with significant potential for computed tomography/photoacoustic tomography bimodal imaging-guided photothermal/photodynamic cancer treatment.

MoS2-Based multipurpose theranostic nanoplatform: realizing dual-imaging-guided combination phototherapy to eliminate solid tumor via a liquefaction necrosis process.

Theranostics that combines the disease diagnosis with treatment is of promising application in the foreground of personalized medicine to achieve a precise treatment with minimum side effects. In this work, we strategically designed a "four-in-one" theranostic nanoplatform for realizing the desired imaging-guided phototherapy, in which functions of fluorescent imaging, photoacoustic imaging tomography (PAT), photothermal therapy (PTT) and photodynamic therapy (PDT) were implemented by bioconjugated MoS2 nanosheets. The protagonist of MoS2 is a light-harvesting material in the near-infrared (NIR) region, which would produce localized hyperthermia at the tumor site to trigger the photothermal therapy effect for the tumor ablation as well as a PAT signal to depict the tumor concurrently upon NIR excitation. To our surprise, MoS2 has been found to be a photosensitizer for the cancer PDT treatment as well. Moreover, bovine serum albumin (BSA) decoration on MoS2 has been made to improve biocompatibility, which also allowed further conjugation with a fluorescent molecule of Cy5.5 to endow the overall nanoplatform with fluorescence imaging and monitoring features. On the basis of the above characters, great successes in cancer imaging and tumor photoablation were achieved in both in vitro and in vivo experiments. Innovatively, B-ultrasonography and MRI imaging were employed to monitor the elimination process of solid tumor after treatment, which clearly revealed a liquefaction necrosis process for rehabilitation. In short, MoS2 represents a nanoplatform of this work and manifested huge advantages in the cancer theranostics.

Highly efficient ablation of metastatic breast cancer using ammonium-tungsten-bronze nanocube as a novel 1064 nm-laser-driven photothermal agent.

Photothermal ablation (PTA) therapy has been viewed as an invasive option for cancer therapy with minimal deconstruction of healthy tissues. In this study, a potent candidate of (NH4)xWO3 nanocube was developed for PTA treatment of metastatic breast cancer in the second near-infrared (NIR) window. It was found that the as-synthesized (NH4)xWO3 nanocube had significant photoabsorption across the whole NIR window of 780-2500 nm and exhibited considerable photo-heat conversion efficiency. Moreover, the as-prepared (NH4)xWO3 nanocube displayed good biocompatibility and high cellular uptake efficiency through endocytosis pathway without nuclei entry. The PTA study employing 1064 nm laser in the second NIR window revealed that (NH4)xWO3 nanocubes induced significant cell necrosis and apoptosis by producing obviously hyperthermia effect inside cancer cells. Using an orthotopicly implanted breast tumor model, it demonstrated that the (NH4)xWO3 nanocube was a promising photothermal agent for effective ablation of solid tumors and suppressing their distant metastasis.

Photothermal ablation cancer therapy using homogeneous CsxWO3 nanorods with broad near-infra-red absorption.

Recently, photothermal ablation therapy (PTA) employing near-infrared radiation (NIR) has been extensively investigated as an emerging modality for cancer management. However, the clinical translation of this promising approach is limited by the lack of PTA agents with broad NIR absorption, low cost and high photothermal conversion efficiency. Herein, we have developed PEGylated homogeneous CsxWO3 nanorods (a mean size ∼69.3 nm × 12.8 nm) with broad photo-absorption (780-2500 nm) as a novel NIR absorbent for PTA treatment of human cancer. The prepared CsxWO3 nanocrystals displayed strong near-infrared optical absorption with a high molar extinction coefficient (e.g. 4.8 × 10(10) M(-1) cm(-1) at 980 nm), thus generated significant amounts of heat upon excitation with near-infrared light. The PTA study in two human carcinoma cell lines (i.e. A549 lung cancer cells and HeLa ovarian cancer cells) demonstrated that CsxWO3 nanorods can efficiently cause cell death via hyperthermia induced lysosome destruction, cytoskeleton protein degradation, DNA damage and thereafter cellular necrosis or apoptosis. Our study also confirmed the migration of healthy cells migrated from unirradiated areas to dead cell cycle, which is essential for tissue reconstruction and wound healing after photodestruction of tumor tissue. The prompted results reported in the current study imply the promising potential of CsxWO3 nanorods for application in PTA cancer therapy.