Mace-Like Plasmonic Au-Pd Heterostructures Boost Near-Infrared Photoimmunotherapy.

Photoimmunotherapy, with spatiotemporal precision and noninvasive property, has provided a novel targeted therapeutic strategy for highly malignant triple-negative breast cancer (TNBC). However, their therapeutic effect is severely restricted by the insufficient generation of tumor antigens and the weak activation of immune response, which is caused by the limited tissue penetration of light and complex immunosuppressive microenvironment. To improve the outcomes, herein, mace-like plasmonic AuPd heterostructures (Au Pd HSs) have been fabricated to boost near-infrared (NIR) photoimmunotherapy. The plasmonic Au Pd HSs exhibit strong photothermal and photodynamic effects under NIR light irradiation, effectively triggering immunogenic cell death (ICD) to activate the immune response. Meanwhile, the spiky surface of Au Pd HSs can also stimulate the maturation of DCs to present these antigens, amplifying the immune response. Ultimately, combining with anti-programmed death-ligand 1 (α-PD-L1) will further reverse the immunosuppressive microenvironment and enhance the infiltration of cytotoxic T lymphocytes (CTLs), not only eradicating primary TNBC but also completely inhibiting mimetic metastatic TNBC. Overall, the current study opens a new path for the treatment of TNBC through immunotherapy by integrating nanotopology and plasmonic performance.

Compositions and Biological Activities of Pomegranate Peel Polyphenols Extracted by Different Solvents.

Pomegranate peel extract (PPE), which is abundant in polyphenols, holds immerse prospects for the treatment of airway infection. In this study, water and ethanol of 30%, 50%, and 80% were used to prepare PPE. A total of 18 phenols belonging to 8 categories of polyphenols were identified in PPE by HPLC-MS/MS. The PPE from the four extraction solvents possessed different antioxidant, antibacterial, and anti-inflammatory activities. Principal component analysis revealed that though total flavonoids (TFs), total polyphenols (TPs), and total tannins (TTs) were responsible for the reducing power of PPE, only TFs contributed to the effect of PPE in inhibiting lipid membrane peroxidation. TPs, TTs, and punicalagin were positively correlated with the antibacterial strength against S. aureus while TTs alone contributed to the inhibition of methicillin-resistant S. aureus, implying the crucial role of TT in suppressing bacteria. Meanwhile, TTs was associated with the prevention of IL-6 release. The PPE with higher contents of TPs, TTs, and punicalagin had a weaker capacity to decrease nitric oxide secretion. PPE of 30% ethanol gained the highest integrated score due to its stronger antioxidant, antibacterial, and anti-inflammatory activities. It is a suitable candidate for the therapy of respiratory tract infection.

Precision hyperthermia-induced miRNA-409-3p upregulation inhibits migration, invasion, and EMT of gastric cancer cells by targeting KLF17.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) is widely used for clinical treatment of advanced cancers. However, the regulatory mechanism underlying precise hyperthermia treatment in advanced gastric cancer (AGC) remains unclear. MiR-409-3p is reportedly downregulated in a variety of cancers, although its role in regulating treatment of AGC by precise hyperthermia remains unclear. The underlying mechanisms of miRNA-medicated regulation have been investigated using predicted and validated miRNA-gene targets, confirming the role of miRNA in HIPEC; METHODS: We used quantitative real time PCR (qRT-PCR) to detect miR-409-3p expression in gastric cancer (GC), as well as adjacent normal tissues, following exposure to varying temperatures. We detected miR-409-3p targets using dual-luciferase assay, then performed cell apoptosis, western blotting, invasion, and migration assays to detect GC functions; RESULTS: MiR-409-3p was upregulated and downregulated in precise hyperthermia and AGC, respectively. Moreover, miR-409-3p upregulated the Krüppel-like-factor 17 (KLF17), which subsequently inhibited migration, invasiveness, and epithelial-mesenchymal transition (EMT) but promoted apoptosis in GC cells; CONCLUSIONS: Precise hyperthermia upregulated miR-409-3p and KLF17 indirectly, thereby inhibiting invasion, migration, and EMT, and promoting apoptosis of gastric cancer cells.

Systems pharmacology reveals the mechanism of activity of Physalis alkekengi L. var. franchetii against lipopolysaccharide-induced acute lung injury.

Acute lung injury (ALI) is an important cause of mortality of patients with sepsis, shock, trauma, pneumonia, multiple transfusions and pancreatitis. Physalis alkekengi L. var. franchetii (Mast.) Makino (PAF) has been extensively used in Chinese folk medicine because of a good therapeutic effect in respiratory diseases. Here, an integrated approach combining network pharmacology, proton nuclear magnetic resonance-based metabolomics, histopathological analysis and biochemical assays was used to elucidate the mechanism of PAF against ALI induced by lipopolysaccharide (LPS) in a mouse model. We found that the compounds present in PAF interact with 32 targets to effectively improve the damage in the lung undergoing ALI. We predicted the putative signalling pathway involved by using the network pharmacology and then used the orthogonal signal correction partial least-squares discriminant analysis to analyse the disturbances in the serum metabolome in mouse. We also used ELISA, RT-qPCR, Western blotting, immunohistochemistry and TUNEL assay to confirm the potential signalling pathways involved. We found that PAF reduced the release of cytokines, such as TNF-α, and the accumulation of oxidation products; decreased the levels of NF-κB, p-p38, ERK, JNK, p53, caspase-3 and COX-2; and enhanced the translocation of Nrf2 from the cytoplasm to the nucleus. Collectively, PAF significantly reduced oxidative stress injury and inflammation, at the same time correcting the energy metabolism imbalance caused by ALI, increasing the amount of antioxidant-related metabolites and reducing the apoptosis of lung cells. These observations suggest that PAF may be an effective candidate preparation alleviating ALI.

Time-staggered delivery of erlotinib and doxorubicin by gold nanocages with two smart polymers for reprogrammable release and synergistic with photothermal therapy.

Photochemotherapy is currently an effective anticancer therapy. Recently, it has been reported that cancer cells pretreated with epidermal growth factor receptor (EGFR) inhibitor erlotinib (Erl) can significantly synergize its apoptosis against the DNA damaging agent doxorubicin (Dox). As a result, we designed two gold nanocages (Au NCs) microcontainers covered with different smart polymer shell-PAA (pH responsive) and p (NIPAM-co-AM) (temperature responsive) containing Erl and Dox respectively. The acidic tumor microenvironment and NIR light irradiation can selectively activate the release of Erl and Dox. Time staggered release of Erl and Dox and photothermal therapy enhance the apoptotic signaling pathways, resulting in improved tumor cell killing in both MCF-7 (low EGFR expression) and A431 (very high EGFR expression) tumor cells, but more efficient in the latter. The photochemotherapy strategy controls the order and duration of drug exposure precisely in spatial and temporal, and significantly improves the therapeutic efficacy against high EGFR expressed tumors.

Anisotropic Plasmonic Metal Heterostructures as Theranostic Nanosystems for Near Infrared Light-Activated Fluorescence Amplification and Phototherapy.

The development of sophisticated theranostic systems for simultaneous near infrared (NIR) fluorescence imaging and phototherapy is of particular interest. Herein, anisotropic plasmonic metal heterostructures, Pt end-deposited Au nanorods (PEA NRs), are developed to efficiently produce hot electrons under 808 nm laser irradiation, exhibiting the strong electric density. These hot electrons can release the heat through electron-phonon relaxation and form reactive oxygen species through chemical transformation, as a result of potent photothermal and photodynamic performance. Simultaneously, the confined electromagnetic field of PEA NRs can transfer energy to adjacent polyethylene glycol (PEG)-linked NIR fluorophores (CF) based on their energy overlap mechanism, leading to remarkable NIR fluorescence amplification in CF-PEA NRs. Various PEG linkers (1, 3.4, 5.0, and 10 kD) are employed to regulate the distance between CF and PEA NRs of CF-PEA NRs, and the maximum fluorescence intensity is achieved in CF5k-PEA NRs. After further attachment with i-motif DNA/Nrf2 siRNA chimera to simultaneously suppress both cellular antioxidant defense and hyperthermia resistance effects, the final biocompatible CF5k-bPEA@siRNA NRs present promising NIR fluorescence imaging ability and 808 nm laser-activated photothermal and photodynamic therapeutic effect in MCF7 cells and tumor-bearing mice, holding great potential for cancer therapy.

Differential photothermal and photodynamic performance behaviors of gold nanorods, nanoshells and nanocages under identical energy conditions.

Various gold (Au) nanostructures have shown promising near infrared (NIR) light-activated phototherapeutic effects; however, their reported photothermal or photodynamic performance behavior is usually inconsistent or even conflicted, dramatically limiting the improvement of phototherapeutic Au nanostructures. The potential reason for this uncertainty is mainly because the photoactivities of Au nanostructures are not evaluated under identical energy conditions. Herein, three Au nanostructures, Au nanorods (NRs), nanoshells (NSs), and nanocages (NCs), were prepared to provide the same localized surface plasmon resonance (LSPR) peaks at 808 nm. All these Au nanostructures (at the same optical density) could fully exert their photoactivities under the identical and optimal energy conditions of 808 nm laser irradiation. It was found that these Au nanostructures could induce similar levels of temperature elevation but different levels of reactive oxygen species (ROS) production, where Au NCs exhibited the highest ROS production, followed by Au NSs and NRs. In vitro and in vivo phototherapeutic assessments further supported that Au NCs could cause the most severe cell death and tumor growth regression. This means that the identical incident energy has different contributions to the photothermal and photodynamic performance of Au nanostructures, and the corner angle structures of Au NCs compared with NSs and NCs could more efficiently convert the photon energy into photodynamic properties. Altogether, Au NCs hold great potential for phototherapy due to their efficient energy utilization capability.

Bismuth Sulfide Nanorods with Retractable Zinc Protoporphyrin Molecules for Suppressing Innate Antioxidant Defense System and Strengthening Phototherapeutic Effects.

Bismuth (Bi)-based nanomaterials (NMs) are widely used for computed tomography (CT) imaging guided photothermal therapy, however, the photodynamic property is hardly exhibited by these NMs due to the fast electron-hole recombination within their narrow bandgap. Herein, a sophisticated nanosystem is designed to endow bismuth sulfide (Bi2 S3 ) nanorods (NRs) with potent photodynamic property. Zinc protoporphyrin IX (ZP) is linked to Bi2 S3 NRs through a thermoresponsive polymer to form BPZP nanosystems. The stretching ZP could prebind to the active site of heme oxygenase-1 overexpressed in cancer cells, suppressing the cellular antioxidant defense capability. Upon NIR laser irradiation, the heat released from Bi2 S3 NRs could retract the polymer and drive ZP to the proximity of Bi2 S3 NRs, facilitating an efficient electron-hole separation in ZP and Bi2 S3 NRs, and leading to reactive oxygen species generation. In vitro and in vivo studies demonstrate the promising photodynamic property of BPZP, together with their photothermal and CT imaging performance.

Resonance Energy Transfer-Promoted Photothermal and Photodynamic Performance of Gold-Copper Sulfide Yolk-Shell Nanoparticles for Chemophototherapy of Cancer.

Gold (Au) core@void@copper sulfide (CuS) shell (Au-CuS) yolk-shell nanoparticles (YSNPs) were prepared in the present study for potential chemo-, photothermal, and photodynamic combination therapy, so-called "chemophototherapy". The resonance energy transfer (RET) process was utilized in Au-CuS YSNPs to achieve both enhanced photothermal and photodynamic performance compared with those of CuS hollow nanoparticles (HNPs). A series of Au nanomaterials as cores that had different localized surface plasmon resonance (LSPR) absorption peaks at 520, 700, 808, 860, and 980 nm were embedded in CuS HNPs to screen the most effective Au-CuS YSNPs according to the RET process. Thermoresponsive polymer was fabricated on these YSNPs' surface to allow for controlled drug release. Au808-CuS and Au980-CuS YSNPs were found capable of inducing the largest temperature elevation and producing the most significant hydroxyl radicals under 808 and 980 nm laser irradiation, respectively, which could accordingly cause the most severe 4T1 cell injury through oxidative stress mechanism. Moreover, doxorubicin-loaded (Dox-loaded) P(NIPAM-co-AM)-coated Au980-CuS (p-Au980-CuS@Dox) YSNPs could more efficiently kill cells than unloaded particles upon 980 nm laser irradiation. After intravenous administration to 4T1 tumor-bearing mice, p-Au980-CuS YSNPs could significantly accumulate in the tumor and effectively inhibit the tumor growth after 980 nm laser irradiation, and p-Au980-CuS@Dox YSNPs could further potentiate the inhibition efficiency and exhibit excellent in vivo biocompatibility. Taken together, this study sheds light on the rational design of Au-CuS YSNPs to offer a promising candidate for chemophototherapy.

Deep-Level Defect Enhanced Photothermal Performance of Bismuth Sulfide-Gold Heterojunction Nanorods for Photothermal Therapy of Cancer Guided by Computed Tomography Imaging.

Bismuth sulfide (Bi2 S3 ) nanomaterials are emerging as a promising theranostic platform for computed tomography imaging and photothermal therapy of cancer. Herein, the photothermal properties of Bi2 S3 nanorods (NRs) were unveiled to intensely correlate to their intrinsic deep-level defects (DLDs) that potentially could work as electron-hole nonradiative recombination centers to promote phonon production, ultimately leading to photothermal performance. Bi2 S3 -Au heterojunction NRs were designed to hold more significant DLD properties, exhibiting more potent photothermal performance than Bi2 S3 NRs. Under 808 nm laser irradiation, Bi2 S3 -Au NRs could trigger higher cellular heat shock protein 70 expression and more apoptotic cells than Bi2 S3 NRs, and caused severe cell death and tumor growth inhibition, showing great potential for photothermal therapy of cancer guided by computed tomography imaging.