In vitro and in vivo MRI imaging and photothermal therapeutic properties of Hematite (α-Fe2O3) Nanorods.

Herein we report synthesis of hematite (α-Fe2O3) nanorods by calcinating hydrothermally synthesized goethite nanorods at 5000C. The structural, optical and MRI imaging guided cancer therapeutic properties of fabricated nanorods have been discussed in this manscript. FESEM and TEM imaging techniques were used to confirm the nanorod like morphology of as prepared materials. As we know that Fe2O3 nanorods with size in the range of 25-30 nm exhibit super magnetism. After coating with the PEG, the as prepared nanorods can be used as T2 MR imaging contrast agents. An excellent T2 MRI contrast of 38.763 mM-1s-1 achieved which is highest reported so far for α-Fe2O3. Besides the as prepared nanorods display an excellent photothermal conversion efficiency of 39.5% thus acts as an excellent photothermal therapeutic agent. Thus, we envision the idea of testing our nanorods for photothermal therapy and MR imaging application both in vitro and in vivo, achieving an excellent T2 MRI contrast and photothermal therapy effect with as prepared PEGylated nanorods.

Multifunctional FeS2@SRF@BSA nanoplatform for chemo-combined photothermal enhanced photodynamic/chemodynamic combination therapy.

Combination therapy has been widely studied due to its promising applications in tumor therapy. However, a sophisticated nanoplatform and sequential irradiation with different laser sources for phototherapy complicate the treatment process. Unlike the integration of therapeutic agents, we report a FeS2@SRF@BSA nanoplatform for the combination of chemo-combined photothermal therapy (PTT) enhanced photodynamic therapy (PDT) and chemodynamic therapy (CDT) to achieve an "all-in-one" therapeutic agent. Ultrasmall FeS2 nanoparticles (NPs) with a size of 7 nm exhibited higher Fenton reaction rates due to their large specific surface areas. A photodynamic reaction could be triggered and could generate 1O2 to achieve PDT under 808 nm irradiation. FeS2 NPs also exhibited the desired photothermal properties under the same wavelength of the laser. The Fenton reaction and photodynamic reaction were both significantly improved to accumulate more reactive oxygen species (ROS) with an increase of temperature under laser irradiation. Besides, loading of the chemotherapeutic drug sorafenib (SRF) further improved the efficacy of tumor treatment. To realize long blood circulation, bovine serum albumin (BSA) was used as a carrier to encapsulate FeS2 NPs and SRF, remarkably improving the biocompatibility and tumor enrichment ability of the nanomaterials. Additionally, the tumors on mice treated with FeS2@SRF@BSA almost disappeared under 808 nm irradiation. To sum up, FeS2@SRF@BSA NPs possess good biocompatibility, stability, and sufficient therapeutic efficacy in combination therapy for cancer treatment. Our study pointed out a smart design of the nanoplatform as a multifunctional therapeutic agent for combination cancer therapy in the near future.

Photoactivation of mitochondrial reactive oxygen species-mediated Src and protein kinase C pathway enhances MHC class II-restricted T cell immunity to tumours.

High fluence low-level laser (HF-LLL), a mitochondria-targeted tumour phototherapy, results in oxidative damage and apoptosis of tumour cells, as well as damage to normal tissue. To circumvent this, the therapeutic effect of low fluence LLL (LFL), a non-invasive and drug-free therapeutic strategy, was identified for tumours and the underlying molecular mechanisms were investigated. We observed that LFL enhanced antigen-specific immune response of macrophages and dendritic cells by upregulating MHC class II, which was induced by mitochondrial reactive oxygen species (ROS)-activated signalling, suppressing tumour growth in both CD11c-DTR and C57BL/6 mice. Mechanistically, LFL upregulated MHC class II in an MHC class II transactivator (CIITA)-dependent manner. LFL-activated protein kinase C (PKC) promoted the nuclear translocation of CIITA, as inhibition of PKC attenuated the DNA-binding efficiency of CIITA to MHC class II promoter. CIITA mRNA and protein expression also improved after LFL treatment, characterised by direct binding of Src and STAT1, and subsequent activation of STAT1. Notably, scavenging of ROS downregulated LFL-induced Src and PKC activation and antagonised the effects of LFL treatment. Thus, LFL treatment altered the adaptive immune response via the mitochondrial ROS-activated signalling pathway to control the progress of neoplastic disease.

Organic optical agents for image-guided combined cancer therapy.

As a promising non-invasive treatment method, phototherapy has attracted extensive attention in the field of combined cancer therapy. Among various optical agents, organic ones have been considered as a promising clinical phototheranostic agent due to its high safety and non-toxic property. In addition, due to the clear structure, facile processability, organic optical agents can be easily endowed with multiple imaging and phototherapeutic functions, significantly simplifying the relatively complex system of imaging-guided combined cancer therapy. This review summarizes the recent research on organic optical agents in imaging-guided combined cancer therapy. The application of organic optical agents in a variety of combined cancer therapeutic modes guided by imaging are introduced respectively, including photodynamic and photothermal combined therapy, phototherapy-combined cancer chemotherapy, and phototherapy-combined cancer immunotherapy. Finally, the concluding remarks and the future prospects are discussed.

Atractylenolide I enhances responsiveness to immune checkpoint blockade therapy by activating tumor antigen presentation.

One of the primary mechanisms of tumor cell immune evasion is the loss of antigenicity, which arises due to lack of immunogenic tumor antigens as well as dysregulation of the antigen processing machinery. In a screen for small-molecule compounds from herbal medicine that potentiate T cell-mediated cytotoxicity, we identified atractylenolide I (ATT-I), which substantially promotes tumor antigen presentation of both human and mouse colorectal cancer (CRC) cells and thereby enhances the cytotoxic response of CD8+ T cells. Cellular thermal shift assay (CETSA) with multiplexed quantitative mass spectrometry identified the proteasome 26S subunit non-ATPase 4 (PSMD4), an essential component of the immunoproteasome complex, as a primary target protein of ATT-I. Binding of ATT-I with PSMD4 augments the antigen-processing activity of immunoproteasome, leading to enhanced MHC-I-mediated antigen presentation on cancer cells. In syngeneic mouse CRC models and human patient-derived CRC organoid models, ATT-I treatment promotes the cytotoxicity of CD8+ T cells and thus profoundly enhances the efficacy of immune checkpoint blockade therapy. Collectively, we show here that targeting the function of immunoproteasome with ATT-I promotes tumor antigen presentation and empowers T cell cytotoxicity, thus elevating the tumor response to immunotherapy.

Time-dependent changes in proliferation, DNA damage and clock gene expression in hepatocellular carcinoma and healthy liver of a transgenic mouse model.

Hepatocellular carcinoma (HCC) is highly resistant to anticancer therapy and novel therapeutic strategies are needed. Chronotherapy may become a promising approach because it may improve the efficacy of antimitotic radiation and chemotherapy by considering timing of treatment. To date little is known about time-of-day dependent changes of proliferation and DNA damage in HCC. Using transgenic c-myc/transforming growth factor (TGFα) mice as HCC animal model, we immunohistochemically demonstrated Ki67 as marker for proliferation and γ-H2AX as marker for DNA damage in HCC and surrounding healthy liver (HL). Core clock genes (Per1, Per2, Cry1, Cry2, Bmal 1, Rev-erbα and Clock) were examined by qPCR. Data were obtained from samples collected ex vivo at four different time points and from organotypic slice cultures (OSC). Significant differences were found between HCC and HL. In HCC, the number of Ki67 immunoreactive cells showed two peaks (ex vivo: ZT06 middle of day and ZT18 middle of night; OSC: CT04 and CT16). In ex vivo samples, the number of γ-H2AX positive cells in HCC peaked at ZT18 (middle of the night), while in OSC their number remained high during subjective day and night. In both HCC and HL, clock gene expression showed a time-of-day dependent expression ex vivo but no changes in OSC. The expression of Per2 and Cry1 was significantly lower in HCC than in HL. Our data support the concept of chronotherapy of HCC. OSC may become useful to test novel cancer therapies.

[Dendritic cell tumor vaccine assisted by Tiaohengfang polysaccharides enhances immune function of S180 tumor-bearing mice and inhibits tumor growth].

Objective To investigate the immunotherapeutic effect and mechanism of dendritic cell (DC) vaccine assisted by Tiaohengfang polysaccharides (ThPP) in S180 tumor-bearing mice. Methods Mouse bone marrow-derived cells were cultured in vitro and mature DCs were obtained with the assistance of cytokines and ThPP. The expression of CD80 and CD86 of DCs induced by ThPP was examined, and S180 tumor cells were used as antigens to stimulate dendritic cells to become dendritic cell tumor vaccine. Tumor-bearing models were established in mice by S180 tumor cells inoculated into the armpit of the left forelimb, and the mice were randomly divided into four groups according to body mass, namely tumor-bearing blank group, positive control group (cyclophosphamide), dendritic cell vaccine group adjuvanted by ThPP and TNF-α. The tumor-bearing mice were treated on the 5th and 10th days after inoculation of tumor cells. The tumor-bearing mice were killed on the 12th day and the tumor inhibition was observed by the tumor mass detection. At the same time, peritoneal macrophages were isolated and cultured, and the expression of CD11b and IL-12 were measured by immunohistochemistry. The levels of serum IL-12 and TNF-α in the mice were detected by ELISA. The survival time of the other four groups of tumor-bearing mice was observed after treatment with the same method. Results The expression of CD80 and CD86 in the TNF-α group and ThPP group were higher than those in the blank control group, and the ThPP group was more significant. The tumor inhibition rate and survival extension period of ThPP, TNF-α and positive groups were significantly higher than those of the model blank group. The levels of serum IL-12 and TNF-α in the ThPP group were higher than those in the positive cyclophosphamide group and model black group. There was no significant difference between the ThPP group and TNF-α group. The expression of CD11b in the macrophages of ThPP group was lower than that in the model blank group and positive group, while the expression of IL-12 in the macrophages of ThPP group was higher than that in the model blank group and positive group, without significant difference compared with TNF-α group. Conclusion ThPP-adjuvanted DC tumor vaccine can inhibit tumor growth and prolong survival time of S180 tumor-bearing mice, which is related to promoting the maturation of DCs and increasing the secretion of IL-12 and TNF-α.

Mitochondria-Targeting Oxygen-Sufficient Perfluorocarbon Nanoparticles for Imaging-Guided Tumor Phototherapy.

BACKGROUND: Although photothermal therapy (PTT) and photodynamics therapy (PDT) have both made excellent progress in tumor therapy, the effectiveness of using PTT or PDT alone is dissatisfactory due to the limitations of the penetration depth in PTT and the hypoxic microenvironment of tumors for PDT. Combination phototherapy has currently become a burgeoning cancer treatment. METHODS AND MATERIALS: In this work, a mitochondria-targeting liquid perfluorocarbon (PFC)-based oxygen delivery system was developed for the synergistic PDT/photothermal therapy (PTT) of cancer through image guiding. RESULTS: Importantly, these nanoparticles (NPs) can effectively and accurately accumulate in the target tumor via the enhanced permeability and retention (EPR) effect. CONCLUSION: This approach offers a novel technique to achieve outstanding antitumor efficacy by an unprecedented design with tumor mitochondria targeting, oxygen delivery, and synergistic PDT/PTT with dual-imaging guidance.

A Nano Drug Delivery System Based on Angelica sinensis Polysaccharide for Combination of Chemotherapy and Immunotherapy.

Combination of chemotherapy and immunotherapy has been a promising strategy in cancer treatment. Polysaccharides from Angelica sinensis (AP), a well-known Chinese herbal medicine, have been proved to have good immunomodulatory activity. In the present study, an enzyme-sensitive tumor-targeting nano drug delivery system (AP-PP-DOX (doxorubicin), PP stood for peptide) was constructed. In this system, Angelica polysaccharides act as not only carriers to targeted delivery of drugs to tumor tissue but also effectors to improve tumor microenvironment and enhance immune function, resulting in synergistic antitumor effect with chemotherapy drugs. The structure of this conjugate was confirmed by FI-IR and 1H-NMR. The particle size and zeta potential of the nanoparticles were 129.00 ± 3.32 nm and -28.45 ± 0.22 mV, respectively. Doxorubicin (DOX) and AP could be quickly released from the AP-PP-DOX under the presence of matrix metalloproteinase 2 (MMP2). The released DOX showed good antitumor efficacy in vitro. The treatment of released AP moiety increased the expression of IL-2, while that of IL-10 was decreased, showing potential in restoring Th1/Th2 immune balance in tumor microenvironment. In a word, this drug delivery system, with specific tissue targeting and tumor microenvironment improvement, will open a new avenue for combination treatment of cancer.

A novel cancer immunotherapy utilizing autologous tumour tissue.

BACKGROUND: With the recent interest in personalized medicine for cancer patients and immune therapy, the field of cancer vaccines has been resurrected. Previous autologous, whole cell tumour vaccine trials have not produced convincing results due, in part to poor patient selection and inactivation methos that are harsh on the cells. These methods can alter protein structure and antigenic profiles making vaccine candidates ineffective in stimulating immune response to autochthonous tumour cells. MATERIALS AND METHODS: We investigated a novel method for inactivating tumour cells that uses UVA/UVB light and riboflavin (vitamin B2) (RF + UV). RF + UV inactivates the tumour cells' ability to replicate, yet preserves tumour cell integrity and antigenicity. RESULTS: Our results demonstrate that proteins are preserved on the surface of RF + UV-inactivated tumour cells and that they are immunogenic via induction of dendritic cell maturation, increase in IFNγ production and generation of tumour cell-specific IgG. Moreover, when formulated with an adjuvant ('Innocell vaccine') and tested in different murine tumour primary and metastatic disease models, decreased tumour growth, decreased metastatic disease and prolonged survival were observed. In addition, immune cells obtained from tumour tissue following vaccination had decreased exhausted and regulatory T cells, suggesting that activation of intra-tumoural T cells may be playing a role leading to reduced tumour growth. CONCLUSIONS: These data suggest that the RF + UV inactivation of tumour cells may provide an efficacious method for generating autologous whole tumour cell vaccines for use in cancer patients.

Clearable Black Phosphorus Nanoconjugate for Targeted Cancer Phototheranostics.

Therapeutic efficacy of synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) is limited by complex conjugation chemistry, absorption wavelength mismatch, and inadequate biodegradability of the PDT-PTT agents. Herein, we designed biocompatible copper sulfide nanodot anchored folic acid-modified black phosphorus nanosheets (BP-CuS-FA) to overcome these limitations, consequently enhancing the therapeutic efficiency of PDT-PTT. In vitro and in vivo assays reveal good biocompatibility and commendable tumor inhibition efficacy of the BP-CuS-FA nanoconjugate because of the synergistic PTT-PDT mediated by near-infrared laser irradiation. Importantly, folic acid unit could target folate receptor overexpressed cancer cells, leading to enhanced cellular uptake of BP-CuS-FA. BP-CuS-FA also exhibits significant contrast effect for photoacoustic imaging, permitting its in vivo tracking. The photodegradable character of BP-CuS-FA is associated with better renal clearance after the antitumor therapy in vivo. The present research may facilitate further development on straightforward approaches for targeted and imaging-guided synergistic PDT-PTT of cancer.

Tumor-targeted near-infrared fluorophore for fluorescence-guided phototherapy.

A tumor-targeted near-infrared (NIR) fluorophore CA800SO3 was developed for fluorescence-guided phototherapy. This new type of NIR fluorophore showed high tumor targetability based on the structure-inherent targeting approach. This fluorophore generated sufficient hyperthermia and reactive oxygen species (ROS) simultaneously for synergistic cancer phototherapy, induced by an 808 nm laser irradiation.

Anti-Tumor Efficacy of an Adjuvant Built-In Nanovaccine Based on Ubiquitinated Proteins from Tumor Cells.

BACKGROUND AND AIM: We have previously identified ubiquitinated proteins (UPs) from tumor cell lysates as a promising vaccine for cancer immunotherapy in different mouse tumor models. In this study, we aimed at developing a highly efficient therapeutic adjuvant built-in nanovaccine (α-Al2O3-UPs) by a simple method, in which UPs from tumor cells could be efficiently and conveniently enriched by α-Al2O3 nanoparticles covalently coupled with Vx3 proteins (α-Al2O3-CONH-Vx3). METHODS: The α-Al2O3 nanoparticles were modified with 4-hydroxybenzoic acid followed by coupling with ubiquitin-binding protein Vx3. It was then used to enrich UPs from 4T1 cell lysate. The stability and the efficiency for the UPs enrichment of α-Al2O3-CONH-Vx3 were examined. The ability of α-Al2O3-UPs to activate DCs was examined in vitro subsequently. The splenocytes from the vaccinated mice were re-stimulated with inactivated tumor cells, and the IFN-γ secretion was detected by ELISA and flow cytometry. Moreover, the therapeutic efficacy of α-Al2O3-UPs, alone and in combination with chemotherapy, was examined in 4T1 tumor-bearing mice. RESULTS: Our results showed that α-Al2O3-UPs were successfully synthesized and abundant UPs from tumor cell lysate were enriched by the new method. In vitro study showed that compared to the physical mixture of α-Al2O3 nanoparticles and UPs (α-Al2O3+UPs), α-Al2O3-UPs stimulation resulted in higher upregulations of CD80, CD86, MHC class I, and MHC class II on DCs, indicating the higher ability of DC activation. Moreover, α-Al2O3-UPs elicited a more effective immune response in mice, demonstrated by higher IFN-γ secretion than α-Al2O3+UPs. Furthermore, α-Al2O3-UPs also exhibited a more potent effect on tumor growth inhibition and survival prolongation in 4T1 tumor-bearing mice. Notably, when in combination with low dose chemotherapy, the anti-tumor effect was further enhanced, rather than using α-Al2O3-UPs alone. CONCLUSION: This study presents an adjuvant built-in nanovaccine generated by a new simple method that can be potentially applied to cancer immunotherapy and lays the experimental foundation for future clinical application.

NIR/Thermoresponsive Injectable Self-Healing Hydrogels Containing Polydopamine Nanoparticles for Efficient Synergistic Cancer Thermochemotherapy.

Injectable and self-healing hydrogels with thermoresponsiveness as smart hydrogels displayed injectability, automatic healing, and phase and volume changes as well. Here, the thermoresponsive self-healing hydrogel was prepared via the formation of dynamic covalent enamine bonds between the amino groups in polyetherimide (PEI) and the acetoacetate groups in the four-armed star-shaped poly(2-(dimethylamino)ethyl methacrylate-co-2-hydroxyethyl methacrylate) modified with tert-butyl acetoacetate (t-BAA), SP(DMAEMA-co-HEMA-AA). After adding polydopamine nanoparticles (PDA NPs), the SP(DMAEMA-co-HEMA-AA)/PEI/PDA-NP nanocomposite hydrogel presented phase change and volume shrinkage under near-infrared (NIR) irradiation. The thermoresponsive nanocomposite hydrogel loaded with the anticancer drug doxorubicin (DOX) could be injected into the 4T1 tumor by intratumoral injection. After NIR laser irradiation, the temperature of the hydrogel increased because of the photothermal effect of PDA NPs inducing local hyperthermia. Because the hydrophilicity-hydrophobicity transition of the hydrogel occurred, DOX molecules were squeezed out from the hydrogel at temperatures higher than its lower critical solution temperature (LCST) and the tumor cells suffered from internal stress from the shrunk hydrogel. The injectable nanocomposite hydrogel not only demonstrated the synergism of highly efficient thermochemotherapy but also showed the function of improving drug utilization and precise treatment to reduce the side effects of drugs.

A trustworthy CpG nanoplatform for highly safe and efficient cancer photothermal combined immunotherapy.

Palladium nanosheets (Pd NSs) have recently attracted increasing research interest in the biomedical field due to their excellent near-infrared absorption, photothermal conversion capability and biocompatibility. However, the application of Pd NSs in immunotherapy has not been reported. Here, Pd NSs were used as the carriers of immunoadjuvant CpG ODNs for not only efficient delivery of CpG but also for enhancing the immunotherapeutic effects of CpG by the Pd NS-based photothermal therapy (PTT). Pd NSs had no influence on the immune system, and the prepared Pd-CpG nanocomposites, especially Pd(5)-CpG(PS), could significantly increase the uptake of CpG by immune cells and enhance the immunostimulatory activity of CpG in vitro and in vivo. With the combination of Pd(5)-CpG(PS) mediated PTT and immunotherapy, highly efficient tumor inhibition was achieved and the survival rate of the tumor-bearing mice was greatly increased depending on Pd(5)-CpG(PS) with safe near-infrared (NIR) irradiation (808 nm laser, 0.15 W cm-2). Importantly, the combination therapy induced tumor cell death and released tumor-associated antigens, which could be effectively taken up and presented by antigen presenting cells with the assistance of CpG, leading to increased TNF-α and IL-6 production and enhanced cytotoxic T lymphocyte (CTL) activity. This work provides a new paradigm of utilizing photothermal nanomaterials for safe and highly efficient cancer photothermal combined immunotherapy.

Gd-/CuS-Loaded Functional Nanogels for MR/PA Imaging-Guided Tumor-Targeted Photothermal Therapy.

The second near-infrared (NIR-II, 1000-1700 nm) light-based diagnosis and therapy have received extensive attention for neoplastic disease treatments because of the fact that light in the NIR-II window possesses less photon scattering along with deeper tissue penetration than that in the NIR-I (700-950 nm) window. Herein, we present a Gd- and copper sulfide (CuS)-integrated nanogel (NG) platform for magnetic resonance (MR)/photoacoustic (PA) imaging-guided tumor-targeted photothermal therapy (PTT). In our approach, we prepared cross-linked polyethylenimine (PEI) NGs via an inverse emulsion method, modified the PEI NGs with Gd chelates, targeting ligand folic acid (FA) through a polyethylene glycol (PEG) spacer and 1,3-propanesultone, and finally loaded CuS nanoparticles (NPs) within the functional NGs. The as-synthesized Gd/CuS@PEI-FA-PS NGs with a mean size of 85 nm exhibit a good water dispersibility and protein resistance property, admirable r1 relaxivity (11.66 mM-1 s-1), excellent NIR-II absorption feature, high photothermal conversion efficiency (26.7%), and FA-mediated targeting specificity to cancer cells overexpressing FA receptor (FAR). With these properties along with the good cytocompatibility, the developed Gd/CuS@PEI-FA-PS NGs enable MR/PA dual-mode imaging-guided targeted PTT of FAR-overexpressing tumors under the irradiation of an NIR-II (1064 nm) laser. The designed Gd/CuS@PEI-FA-PS NGs may be used as a promising theranostic agent for MR/PA dual-mode imaging-guided PTT of other FAR-expressing tumors.

Injectable in Situ Forming Hydrogels of Thermosensitive Polypyrrole Nanoplatforms for Precisely Synergistic Photothermo-Chemotherapy.

The combination of photothermal therapy (PTT) with chemotherapy has great potential to maximize the synergistic effect of thermo-induced chemosensitization and improve treatment performance. To achieve high drug-loading capacity as well as precise synchronization between the controllable release of chemotherapeutics and the duration of near-infrared PTT, in this work, a facile one-step method was first developed to fabricate a novel injectable in situ forming photothermal modulated hydrogel drug delivery platform (D-PPy@PNAs), in which a PNIPAM-based temperature-sensitive acidic triblock polymer [poly(acrylic acid-b-N-isopropylamide-b-acrylic acid (PNA)] was utilized as the stabilizing agent in the polymerization of polypyrrole (PPy). The in situ forming hydrogels showed a sensitive temperature-responsive sol-gel phase-transition behavior, as well as an excellent photothermal property. The strong interaction of ionic bonds together with π-π stacking interactions resulted in high doxorubicin (DOX) loading capacity and controlled/sustained drug release behavior. In addition, D-PPy@PNAs also displayed enhanced cellular uptake and promoted intratumoral penetration of DOX upon NIR laser irradiation. The synergistic photothermal therapy-chemotherapy of D-PPy@PNA hydrogels greatly improved the antitumor efficacy in vivo. Therefore, thermosensitive polypyrrole-based D-PPy@PNA hydrogels may be powerful drug delivery nanoplatforms for precisely synergistic photothermo-chemotherapy of tumors.

Combined Magnetic Hyperthermia and Immune Therapy for Primary and Metastatic Tumor Treatments.

Cancer immunotherapy shows promising potential in future cancer treatment but unfortunately is clinically unsatisfactory due to the low therapeutic efficacy and the possible severe immunotoxicity. Here we show a combined magnetic hyperthermia therapy (MHT) and checkpoint blockade immunotherapy for both primary tumor ablation and mimetic metastatic tumor inhibition. Monodispersed, high-performance superparamagnetic CoFe2O4@MnFe2O4 nanoparticles were synthesized and used for effective MHT-induced thermal ablation of primary tumors. Simultaneously, numerous tumor-associated antigens were produced to promote the maturation and activation of dendritic cells (DCs) and cytotoxic T cells for effective immunotherapy of distant mimetic metastatic tumors in a tumor-bearing mice model. The combined MHT and checkpoint blockade immunotherapy demonstrate the great potentials in the fight against both primary and metastatic tumors.

A glutathione-depleting chemodynamic therapy agent with photothermal and photoacoustic properties for tumor theranostics.

Nowadays, Fenton reaction-based chemodynamic therapy (CDT) strategies have drawn extensive attention as tumor-specific nanomedicine-based therapy. Nevertheless, current existing CDTs normally suffer from therapeutic bottlenecks such as the scavenging of hydroxyl radical (˙OH) by intracellular antioxidants and unideal therapeutic outcome of single treatment modality. Herein, we constructed novel all-in-one AFP nanoparticles (NPs) as CDT agents through a one-pot process for multifunctional nanotheranostics. The as-constructed AFP NPs could simultaneously produce ˙OH through the Fenton reaction and scavenge intracellular glutathione, functioning as self-reinforced CDT agents to achieve tumor-triggered enhanced CDT (ECDT). In addition, the AFP NPs possessed the capability of H2O2 and acid-boosted photoacoustic imaging and photothermal therapy, enabling a precise and effective tumor therapeutic outcome with minimal nonspecific damage in combination with ECDT. Our novel nanoplatform would open new perspectives on multi-functional CDT agents for accurate and non-invasive tumor theranostics.

Synthesis of gold-silica core-shell nanoparticles by pulsed laser ablation in liquid and their physico-chemical properties towards photothermal cancer therapy.

Due to the increasing scientific and biomedical interest in various nanoparticles (NPs) with excellent properties and the onset of their commercial use, a convenient and adjustable physical method for improved efficiency needs to be used for enabling their tech-scale production. Recently, great progress has been made in the large-scale production of NPs with a simple structure by pulsed laser ablation in liquid (PLAL). In this work, we synthesized gold-silica core-shell NPs by improved PLAL and provided a guide on how to investigate their physico-chemical properties and association with biological effects towards cancer photothermal therapy (PTT). By means of this method, reproducible and scalable liquid phase NPs with less toxicity and good stability can be realized for tech-scale production based on its further adjustment and modification. Moreover, a more complete investigation of the associations between the physico-chemical properties of functional NPs with complex structure and their biological effects may enable more targeted NPs towards specific requirements of biomedical applications.