Bypassing Ca Influx for Antimetastasis Photodynamic Therapy via Robust Nucleus-Targeted Near-Infrared Cyanines.

Hypoxia-induced tumor metastasis severely hinders the efficacy of photodynamic therapy (PDT) in cancer treatment. Current strategies predominantly offer palliative suppression of the HIF-1α pathway, emphasizing the urgent need for innovative PDT approaches to prevent metastasis from the outset. Our study revealed that typical PDT triggers an increase in cytoplasmic Ca levels, activating HIF-1α, and that reducing Ca levels can, in turn, mitigate metastasis.

Injectable Autocatalytic Hydrogel Triggers Pyroptosis to Stimulate Anticancer Immune Response for Preventing Postoperative Tumor Recurrence.

Modulating immunosuppression while eliminating residual microscopic tumors is critical for inhibiting the postoperative recurrence of triple-negative breast cancer (TNBC). Although immunotherapy has shown potential in achieving this goal, due to multiple immunosuppression and poor immunogenicity of apoptosis, a satisfactory anti-recurrence effect still faces the challenge. Herein, an injectable hydrogel-encapsulated autocatalytic copper peroxide (CP@Gel) therapeutic platform is designed and combine it with the clinical-grade DNA methyltransferase inhibitor decitabine (DAC) to effectively inhibit TNBC growth and postoperative recurrence via pyroptosis, killing residual cancer cells that bypass apoptosis resistance while also improving immunogenicity and modulating immunosuppression to achieve an intense anti-tumor immune response.

Genetically engineered macrophages as living cell drug carriers for targeted cancer therapy.

Precise targeting is a major prerequisite for effective cancer therapy because it ensures a sufficient therapeutic dosage in tumors while minimizing off-target side effects. Herein, we report a live-macrophage-based therapeutic system for high-efficiency tumor therapy. As a proof of concept, anti-human epidermal growth factor receptor-2 (HER2) affibodies were genetically engineered onto the extracellular membrane of macrophages (AE-Mφ), which further internalized doxorubicin (DOX)-loaded poly(lactic-co-glycolic acid) nanoparticles (NPs) to produce a macrophage-based therapeutic system armed with anti-HER2 affibodies.

Filamentous-Actin-Mimicking Nanoplatform for Enhanced Cytosolic Protein Delivery.

Despite the potential of protein therapeutics, the cytosolic delivery of proteins with high efficiency and bioactivity remains a significant challenge owing to exocytosis and lysosomal degradation after endocytosis. Therefore, it is important to develop a safe and efficient strategy to bypass endocytosis. Inspired by the extraordinary capability of filamentous-actin (F-actin) to promote cell membrane fusion, a cyanine dye assembly-containing nanoplatform mimicking the structure of natural F-actin is developed.

Gene Reprogramming Armed Macrophage Membrane-Camouflaged Nanoplatform Enhances Bionic Targeted Drug Delivery to Solid Tumor for Synergistic Therapy.

Efficient drug delivery to solid tumors remains a challenge. HER2-positive (HER2) tumors are an aggressive cancer subtype with a resistance to therapy, high risk of relapse, and poor prognosis. Although nanomedicine technology shows obvious advantages in tumor treatment, its potential clinical translation is still impeded by the unsatisfactory delivery and therapeutic efficacy.

Engineered Macrophages-Based uPA-Scavenger Load Gemcitabine to Prompt Robust Treating Cancer Metastasis.

The majority of cancer patients die of metastasis rather than primary tumors, and most patients may have already completed the cryptic metastatic process at the time of diagnosis, making them intractable for therapeutic intervention. The urokinase-type plasminogen activator (uPA) system is proved to drive cancer metastasis. However, current blocking agents such as uPA inhibitors or antibodies are far from satisfactory due to poor pharmacokinetics and especially have to face multiplex mechanisms of metastasis.

Post-Remedial Oxygen Supply: A New Perspective on Photodynamic Therapy to Suppress Tumor Metastasis.

Photodynamic therapy (PDT) holds great promise in tumor therapy due to high safety, efficacy, and specificity. However, the risk of increased metastasis in hypoxic tumors after oxygen-dependent PDT remains underestimated. Here, we propose a post-PDT oxygen supply (POS) strategy to reduce the risk of metastasis.

Liposome-templated gold nanoparticles for precisely temperature-controlled photothermal therapy based on heat shock protein expression.

Mild temperature photothermal therapy is gaining more and more attention due to high safety, high specificity and moderate efficacy. However, the therapeutical outcome of mild photothermal therapy is limited due to the overexpression of heat shock proteins (HSPs). Therefore, the precise management of HSP expression is the key to improvement of mild temperature photothermal therapy.

Bioorthogonally activatable cyanine dye with torsion-induced disaggregation for in vivo tumor imaging.

Advancement of bioorthogonal chemistry in molecular optical imaging lies in expanding the repertoire of fluorophores that can undergo fluorescence signal changes upon bioorthogonal ligation. However, most available bioorthogonally activatable fluorophores only emit shallow tissue-penetrating visible light via an intramolecular charge transfer mechanism. Herein, we report a serendipitous "torsion-induced disaggregation (TIDA)" phenomenon in the design of near-infrared (NIR) tetrazine (Tz)-based cyanine probe.

Development and validation of a PCR-free nucleic acid testing method for RNA viruses based on linear molecular beacon probes.

Background: RNA viruses periodically trigger pandemics of severe human diseases, frequently causing enormous economic losses. Here, a nucleic acid extraction-free and amplification-free RNA virus testing probe was proposed for the sensitive and simple detection of classical swine fever virus (CSFV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), based on a double-stranded molecular beacon method. This RNA virus probe contains two base sequences-a recognition strand that binds to the specific domain of CSFV N2 or SARS-CoV-2 N, with a fluorophore (FAM) labeled at the 5' end, and a complementary strand (CSFV-Probe B or SARS-CoV-2-Probe B), combined with a quencher (BHQ2) labeled at the 3' end.

Pyroptosis in inflammatory diseases and cancer.

Pyroptosis is a lytic and inflammatory type of programmed cell death that is usually triggered by inflammasomes and executed by gasdermin proteins. The main characteristics of pyroptosis are cell swelling, membrane perforation, and the release of cell contents. In normal physiology, pyroptosis plays a critical role in host defense against pathogen infection.

Liposomal Glucose Oxidase for Enhanced Photothermal Therapy and Photodynamic Therapy against Breast Tumors.

Organic near-infrared fluorescent dye mediated photothermal therapy (PTT) and photodynamic therapy (PDT) suffer from heat shock response, since, heat shock proteins (HSPs) are overexpressed and can repair the proteins damaged by PTT and PDT. Starvation therapy by glucose oxide (GOx) can inhibit the heat shock response by limiting the energy supply. However, the delivery of sufficient and active GOx remains a challenge.

Insight into the spatial interaction of D-π-A bridge derived cyanines and nitroreductase for fluorescent cancer hypoxia detection.

Nitroreductase (NTR) detection in tumor is critical because NTR level is correlated with hypoxia degree and cancer prognosis. With the feature of high sensitivity and selectivity, fluorescence organic probes for NTR detection exhibited a promising future for tumor hypoxia detection. However, the discovery and design of such probes have been impeded due to the lack of the understanding of spatial match and mismatch of these probes with NTR.

Recent progress in drug delivery and cancer theranostic built from metal-organic framework.

With the improvement of living standards, cancer has become a great challenge around the world during last decades, meanwhile, abundant nanomaterials have been developed as drug delivery system (DDS) or cancer theranostic agents (CTAs) with their outstanding properties. However, low multifunctional efficiency and time-consuming synthesis limit their further applications. Nowadays, green chemistry, in particular, the concept of atom economy, has defined new criteria for the simplicity and efficient production of biomaterials for nanomedicine, which not only owns the property of spatio-temporal precision imaging, but also possess the ability to treat cancer.

Albumin-based fluorescence resonance energy transfer nanoprobes for multileveled tumor tissue imaging and dye release imaging.

Tumor tissue imaging and drug release imaging are both crucial for tumor imaging and image-guided drug delivery. It is urgent to develop a multileveled tumor imaging platform to realize the multiple imaging applications. In this work, we synthesized an albumin-based fluorescence resonance energy transfer (FRET) probe Cy5/7@HSA NPs containing two near-infrared cyanine dyes (CyBI5 and CyBI7) with high FRET efficiency (97 %).

Engineering Macrophages for Cancer Immunotherapy and Drug Delivery.

Macrophages play an important role in cancer development and metastasis. Proinflammatory M1 macrophages can phagocytose tumor cells, while anti-inflammatory M2 macrophages such as tumor-associated macrophages (TAMs) promote tumor growth and invasion. Modulating the tumor immune microenvironment through engineering macrophages is efficacious in tumor therapy.

Calming the Cytokine Storm in Pneumonia by Biomimetic Nanoparticles.

Recently, the Wang group at Soochow University and the Gu group at the University of California, Los Angeles demonstrated the targeting ability of platelet-derived extracellular vesicles to deliver anti-inflammatory drug [5-(-fluorophenyl)-2-ureido] thiophene-3-carboxamide (TPCA-1) to pneumonia for calming the local cytokine storm in acute lung injury.

An activatable liposomal fluorescence probe based on fluorescence resonance energy transfer and aggregation induced emission effect for sensitive tumor imaging.

Liposomes are of great interest and importance in tumor imaging, since they can greatly improve the imaging sensitivity and specificity by increasing the accumulation of contrast agents. Still, most liposome-based probes have high background signals during blood circulation, which limits enhancement of S/B ratio and tumor imaging sensitivity. To enhance the S/B ratio of tumor imaging, we construct a fluorescence resonance energy transfer (FRET) and aggregation induced emission (AIE) based liposomal fluorescence probe TPE/BHQ-lipo with excellent FRET effect (99 %) and great fluorescence enhancement upon liposome rupture (120-fold) as well as efficient fluorescence recovery in tumor cell imaging.

Liposome-based probes for molecular imaging: from basic research to the bedside.

Molecular imaging is very important in disease diagnosis and prognosis. Liposomes are excellent carriers for different types of molecular imaging probes. In this work, we summarize current developments in liposome-based probes used for molecular imaging and their applications in image-guided drug delivery and tumour surgery, including computed tomography (CT), ultrasound imaging (USI), magnetic resonance imaging (MRI), positron emission tomography (PET), fluorescence imaging (FLI) and photoacoustic imaging (PAI).

Development of functionalized gold nanoparticles as nanoflare probes for rapid detection of classical swine fever virus.

Classical swine fever (CSF) is a devastating viral disease affecting pigs that causes major economic losses worldwide. Conventional assays to identify classical swine fever virus (CSFV) face challenges, such as the required molecular amplification of the target molecules via polymerase chain reaction (PCR). We designed a gold nanoflare probe to directly detect CSFV.

In Vivo and in Situ Activated Aggregation-Induced Emission Probes for Sensitive Tumor Imaging Using Tetraphenylethene-Functionalized Trimethincyanines-Encapsulated Liposomes.

The design and exploration of fluorescent probes with high-sensitivity and low-background are essential for noninvasive optical molecular imaging. The in vivo and in situ activated aggregation-induced emission (AIE) probes were found to be ideal for achieving higher signal-to-background ratios for tumor detections. We herein developed novel tetraphenylethene-encapsulated liposomes (TPE-LPs) constructed by loading TPE-trimethincyanine into liposomes for the first time, and the probes were applied to tumor bioimaging in vivo.

pH sensitive liposomes delivering tariquidar and doxorubicin to overcome multidrug resistance of resistant ovarian cancer cells.

Multidrug resistance of tumour cells is one of the most important hurdles in tumour chemotherapy. To overcome the multidrug resistance, we constructed a pH-sensitive liposome formulation (pHSL) by loading tariquidar (TQR) and DOX simultaneously in this work. The formulation showed high stability at pH 7.

Integrated genomic analyses of lung squamous cell carcinoma for identification of a possible competitive endogenous RNA network by means of TCGA datasets.

The etiology of cancer includes aberrant cellular homeostasis where a compromised RNA regulatory network is a prominent contributing factor. In particular, noncoding RNAs including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) were recently shown to play important roles in the initiation, progression, and metastasis of human cancers. Nonetheless, a mechanistic understanding of noncoding RNA functions in lung squamous cell carcinoma (LUSC) is lacking.

A polycation coated liposome as efficient siRNA carrier to overcome multidrug resistance.

Multidrug resistance (MDR) is one of the important factors that impede effective chemotherapy against cancer. Codelivery of MDR1 siRNA (silencing ABCB1 gene) and anticancer drug can greatly inhibit tumor proliferation. Here in this work, we synthesized poly(diallyldimethylammonium chloride) (PDADMAC) coated liposome formula as siMDR1 carrier (AL-PDAD-RNA) and applied it to reverse doxorubicin resistance of OVCAR8/ADR cells.