Dual Polarization Strategy for Boosting Electron-Hole Separation toward Overall Water Splitting within Ferroelectric ß-AIBIIIO2 (BIII = P3+, As3+, Sb3+, and Bi3+ for Lone Pairs).

Ferroelectric materials, leveraging an inherent built-in electric field, are excellent in suppressing electron-hole recombination. However, the reliance solely on bulk polarization remains insufficient in enhancing carriers' separation and migration, limiting their practical application in photocatalytic overall water splitting (POWS). To address this, we incorporated cations with ns2 lone pairs (P3+, As3+, Sb3+, and Bi3+) into ferroelectric semiconductors, successfully constructing 44 ß-AIBIIIO2 photocatalysts with dual polarization. Through rigorous first-principles calculations and screenings for stability, band characteristics, and polarization, we identified four promising candidates: ß-LiSbO2, ß-NaSbO2, ß-LiBiO2, and ß-TlBiO2. Within these materials, lone pairs induce local polarization in the xy-plane. Additionally, out of the plane, there is robust bulk polarization along the z-direction. This synergistic effect of the combined local and bulk polarization significantly improves the separation efficiency of electron-hole pairs. Explicitly, the electron mobility of the four candidates ranges from 105 to 106 cm2 s-1 V-1, while the hole mobility also increases significantly compared to single-phase polarized materials, up to 106 cm2 s-1 V-1. Notably, ß-TlBiO2 is predicted to achieve a solar-to-hydrogen (STH) efficiency of 17.2%. This study not only offers insights for water-splitting catalyst screening but also pioneers a path for electron-hole separation through the dual polarization strategy.

A Long-Acting Lyotropic Liquid Crystalline Implant Promotes the Drainage of Macromolecules by Brain-Related Lymphatic System in Treating Aged Alzheimer's Disease.

Numerous evidence has demonstrated that the brain is not an immune-privileged organ but possesses a whole set of lymphatic transport system, which facilitates the drainage of harmful waste from brains to maintain cerebral homeostasis. However, as individuals age, the shrinkage and dysfunction of meningeal and deep cervical lymphatic networks lead to reduced waste outflow and elevated neurotoxic molecules deposition, further inducing aging-associated cognitive decline, which act as one of the pathological mechanisms of Alzheimer's disease. Consequently, recovering the function of meningeal and deep cervical lymph node (dCLNs) networks (as an important part of the brain waste removal system (BWRS)) of aged brains might be a feasible strategy. Herein we showed that the drug brain-entering efficiency was highly related to administration routes (oral, subcutaneous, or dCLN delivery). Besides, by injecting a long-acting lyotropic liquid crystalline implant encapsulating cilostazol (an FDA-approved selective PDE-3 inhibitor) and donepezil hydrochloride (a commonly used symptomatic relief agent to inhibit acetylcholinesterase for Alzheimer's disease) near the deep cervical lymph nodes of aged mice (about 20 months), an increase of lymphatic vessel coverage in the nodes and meninges was observed, along with accelerated drainage of macromolecules from brains. Compared with daily oral delivery of cilostazol and donepezil hydrochloride, a single administered dual drugs-loaded long-acting implants releasing for more than one month not only elevated drug concentrations in brains, improved the clearing efficiency of brain macromolecules, reduced Aß accumulation, enhanced cognitive functions of the aged mice, but improved patient compliance as well, which provided a clinically accessible therapeutic strategy toward aged Alzheimer's diseases.

A nanoemulsion targeting adipose hypertrophy and hyperplasia shows anti-obesity efficiency in female mice.

Obesity often leads to severe medical complications. However, existing FDA-approved medications to combat obesity have limited effectiveness in reducing adiposity and often cause side effects. These medications primarily act on the central nervous system or disrupt fat absorption through the gastrointestinal tract. Adipose tissue enlargement involves adipose hyperplasia and hypertrophy, both of which correlate with increased reactive oxygen species (ROS) and hyperactivated X-box binding protein 1 (XBP1) in (pre)adipocytes. In this study, we demonstrate that KT-NE, a nanoemulsion loaded with the XBP1 inhibitor KIRA6 and α-Tocopherol, simultaneously alleviates aberrant endoplasmic reticulum stress and oxidative stress in (pre)adipocytes. As a result, KT-NE significantly inhibits abnormal adipogenic differentiation, reduces lipid droplet accumulation, restricts lipid droplet transfer, impedes obesity progression, and lowers the risk of obesity-associated non-alcoholic fatty liver disease in female mice with obesity. Furthermore, diverse administration routes of KT-NE impact its in vivo biodistribution and contribute to localized and/or systemic anti-obesity effectiveness.

Precisely Regulating M2 Subtype Macrophages for Renal Fibrosis Resolution.

Macrophages are central to the pathogenesis of kidney disease and serve as an effective therapeutic target for kidney injury and fibrosis. Among them, M2-type macrophages have double-edged effects regarding anti-inflammatory effects and tissue repair. Depending on the polarization of the M2 subtypes (M2a or M2c) in the diseased microenvironment, they can either mediate normal tissue repair or drive tissue fibrosis. In renal fibrosis, M2a promotes disease progression through macrophage-to-myofibroblast transition (MMT) cells, while M2c possesses potent anti-inflammatory functions and promotes tissue repair, and is inhibited. The mechanisms underlying this differentiation are complex and are currently not well understood. Therefore, in this study, we first confirmed that M2a-derived MMT cells are responsible for the development of renal fibrosis and demonstrated that the intensity of TGF-ß signaling is a major factor determining the differential polarization of M2a and M2c. Under excessive TGF-ß stimulation, M2a undergoes a process known as MMT cells, whereas moderate TGF-ß stimulation favors the polarization of M2c phenotype macrophages. Based on these findings, we employed targeted nanotechnology to codeliver endoplasmic reticulum stress (ERS) inhibitor (Ceapin 7, Cea or C) and conventional glucocorticoids (Dexamethasone, Dex or D), precisely modulating the ATF6/TGF-ß/Smad3 signaling axis within macrophages. This approach calibrated the level of TGF-ß stimulation on macrophages, promoting their polarization toward the M2c phenotype and suppressing excessive MMT polarization. The study indicates that the combination of ERS inhibitor and a first-line anti-inflammatory drug holds promise as an effective therapeutic approach for renal fibrosis resolution.

Antioxidant nanoemulsion loaded with latanoprost enables highly effective glaucoma treatment.

Glaucoma is the third leading cause of blindness worldwide and is primarily characterized by elevated intraocular pressure (IOP). Common risk factors such as age, myopia, ocular trauma, and hypertension all increase the risk of elevated IOP. Prolonged high IOP not only causes physiological discomfort like headaches, but also directly damages retinal cells and leads to retinal ischemia, oxidative imbalance, and accumulation of reactive oxygen species (ROS) in the retina. This oxidative stress causes the oxidation of proteins and unsaturated lipids, leading to peroxide formation and exacerbating retinal damage. While current clinical treatments primarily target reducing IOP through medication or surgery, there are currently no effective methods to mitigate the retinal cell damage associated with glaucoma. To address this gap, we developed a novel nanoemulsion to co-delivery latanoprost and α-tocopherol (referred to as LA@VNE later) that prolongs ocular retention and enhances retinal permeability through localized administration. By encapsulating latanoprost, an IOP-lowering drug, and α-tocopherol, a potent antioxidant, we effectively reduced ROS accumulation (>1.5-fold in vitro and 2.5-fold in vivo), retinal ganglion cell (RGC) apoptosis (>9 fold), and inflammatory cell infiltration (>1.6 fold). Our approach showed strong biocompatibility and significant potential for clinical translation, providing a promising platform for the treatment of glaucoma.

Financial asset allocation duality and enterprise upgrading: empirical evidence from the Chinese A-share market.

This study selects the financial data of Chinese non-financial listed companies from 2012 to 2021 as the research sample and empirically examines in detail the impact of financial asset allocation on enterprise upgrading and its mechanism. The study finds that financial assets have a dual influence on enterprise upgrading. Short-term financial assets provide the necessary funds for production activities, thus promoting enterprise upgrading. Long-term financial assets crowd out the funds needed for production activities and thus inhibit enterprise upgrading, resulting in an inverted U-shaped relationship between financial assets and enterprise upgrading. Mechanism testing revealed that risk-taking capacity and earnings persistence are important ways in which financial assets affect enterprise upgrading. In addition, the impact of financial assets on enterprise upgrading differs for different types of financial assets. The financial asset significantly impacts the upgrading of over-indebtedness, non-state-owned, and high financing constraints enterprises. This study enriches the research literature on financial assets and enterprise upgrading and provides new micro evidence for understanding the impact of financial assets on the enterprise upgrading of listed companies.

Neutrophil hitchhiking for drug delivery to the bone marrow.

Pharmaceuticals have been developed for the treatment of a wide range of bone diseases and disorders, but suffer from problematic delivery to the bone marrow. Neutrophils are naturally trafficked to the bone marrow and can cross the bone marrow-blood barrier. Here we report the use of neutrophils for the targeted delivery of free drugs and drug nanoparticles to the bone marrow. We demonstrate how drug-loaded poly(lactic-co-glycolic acid) nanoparticles are taken up by neutrophils and are then transported across the bone marrow-blood barrier to boost drug concentrations in the bone marrow. We demonstrate application of this principle to two models. In a bone metastasis cancer model, neutrophil delivery is shown to deliver cabazitaxel and significantly inhibit tumour growth. In an induced osteoporosis model, neutrophil delivery of teriparatide is shown to significantly increase bone mineral density and alleviate osteoporosis indicators.

A Clinically-Achievable Injectable and Sprayable in Situ Lyotropic Liquid Crystalline Platform in Treating Hormone-Sensitive and Castration-Resistant Prostate Cancer.

When it comes to long-acting injections, lyotropic liquid crystals (LLCs) are considered as an effective and powerful drug delivery technology due to their low manufacturing and injection difficulty, consistent releasing behaviors with low burst, as well as broadly applicable drug loading capacity. However, monoolein and phytantriol, as two widely used LLC-forming materials, may give rise to tissue cytotoxicity and undesired immunological responses, which may hinder the wide application of this technology. In this study, we opted for two ingredients, phosphatidylcholine and α-tocopherol, as carriers on account of their nature-obtainable and biocompatible qualities. By changing the ratios between them, we conducted research on crystalline types, nanosized structures, viscoelastic differences, characteristics of releasing behaviors, and in vivo safety. To fully exploit this in situ LLC platform with both injectability and sprayability, we focused on the treatment of both hormone-sensitive (HSPC) and castration-resistant prostate cancer (CRPC). For HSPC, we found that spraying leuprolide and a cabazitaxel-loaded LLC platform on the tumor bed after resection greatly reduced tumor metastatic rate and prolonged the survival time. Besides, for CRPC, our results demonstrated that although leuprolide (a kind of drug for castration) alone could hardly limit the progression of CRPC with low MHC-I expression, its combination with cabazitaxel in our LLC platform achieved a significantly better tumor-inhibiting and anti-recurrent efficacy than single cabazitaxel-loaded LLC platform, owing to enhanced CD4+ T cell infiltration in tumors and immune-potentiating cytokines. In conclusion, our dual-functional and clinically achievable strategy might provide a treating solution toward both HSPC and CRPC.

Recruiting T cells and sensitizing tumors to NKG2D immune surveillance for robust antitumor immune response.

Although recruiting T cells to convert cold tumors into hot can prevent some tumors from evading immune surveillance, tumors have evolved more mechanisms to achieve immune evasion, such as downregulating major histocompatibility complex I (MHC I) molecules expression to prevent T cells from recognizing tumor-antigens, or secreting immune suppression cytokines that disable T cells. Tumor immune evasion not only promotes tumor growth, but also weakens the efficacy of existing tumor immunotherapies. Therefore, recruiting T cells while reshaping innate immunity plays an important role in preventing tumor immune escape. In this study, we constructed a long-acting in situ forming implant (ISFI) based on the Atrigel technology, co-encapsulated with G3-C12 and sulfisoxazole (SFX) as a drug depot in the tumor site (SFX + G3-C12-ISFI). First, G3-C12 could recruit T cells, and transform cold into hot tumors. Furthermore, SFX could inhibit tumor-derived exosomes secretion, reduce the shedding of NKG2D ligand (NKG2DL), repair NKG2D/NKG2DL pathway, reinvigorate natural killer (NK) cells, and evade the effects of MHC I molecules missing. In the humanized cold tumor model, our strategy showed an excellent anti-tumor effect, providing a smart strategy for solving tumor evasion immune surveillance.

Nonlysosomal Route of mRNA Delivery and Combining with Epigenetic Regulation Optimized Antitumor Immunoprophylactic Efficacy.

Currently, mRNA-based tumor therapies are in full flow because in vitro-transcribed (IVT) mRNA has the potential to express tumor antigens to initiate the adaptive immune responses. However, the efficacy of such therapy relies heavily on the delivery system. Here, a pardaxin-modified liposome loaded with tumor antigen-encoding mRNA and adjuvant (2',3'-cGAMP, (cyclic [G(2',5')pA(3',5')p])), termed P-Lipoplex-CDN is reported. Due to an nonlysosomal delivery route, the transfection efficiency on dendritic cells (DCs) is improved by reducing the lysosome disruption of cargos. The mRNA modified DCs efficiently induce tumor antigen-specific immune responses both in vitro and in vivo. As prophylactic vaccines, mRNA transfected DCs significantly delay the occurrence and development of tumors, and several immunized mice are even completely resistant to tumors. Interestingly, the efficacy depends on the major histocompatibility complex class I (MHC-I) expression level on tumor cells. Furthermore, epigenetic modification (decitabine, DAC) is applied as a combination strategy to deal with malignant tumor progression caused by deficient tumor MHC-I expression. This study highlights the close relationship between mRNA-DCs vaccine efficacy and the expression level of tumor cell MHC-I molecules. Moreover, a feasible strategy for tumor MHC-I expression deficiency is proposed, which may provide clinical guidance for the design and application of mRNA-based tumor therapies.

Structural and biochemical characteristics of mRNA nanoparticles determine anti-SARS-CoV-2 humoral and cellular immune responses.

The coronavirus disease 2019 (COVID-19) pandemic underlines the urgent need for effective mRNA vaccines. However, current understanding of the immunological outcomes of mRNA vaccines formulated under different nanoplatforms is insufficient. Here, severe acute respiratory syndrome coronavirus 2 receptor binding domain mRNA delivered via lipid nanoparticle (LNP), cationic nanoemulsion (CNE), and cationic liposome (Lipo) was constructed. Results demonstrated that the structural and biochemical characteristics of nanoparticles shaped their tissue dissemination, cellular uptake, and intracellular trafficking, which eventually determined the activation of antiviral humoral and cellular immunity. Specifically, LNP was mainly internalized by myocyte and subsequently circumvented lysosome degradation, giving rise to humoral-biased immune responses. Meanwhile, CNE and Lipo induced cellular-preferred immunity, which was respectively attributed to the better lysosomal escape in dendritic cells and the superior biodistribution in secondary lymphoid organs. Overall, this study may guide the design and clinical use of mRNA vaccines against COVID-19.

Arginine Supplementation Targeting Tumor-Killing Immune Cells Reconstructs the Tumor Microenvironment and Enhances the Antitumor Immune Response.

The tumor microenvironment (TME) is characterized by several immunosuppressive factors, of which weak acidity and l-arginine (l-arg) deficiency are two common features. A weak acidic environment threatens the survival of immune cells, and insufficient l-arg will severely restrain the effect of antitumor immune responses, both of which affect the efficiency of cancer treatments (especially immunotherapy). Meanwhile, l-arg is essential for tumor progression. Thus, two strategies, l-arg supplementation and l-arg deprivation, are developed for cancer treatment. However, these strategies have the potential risk of promoting tumor growth and impairing immune responses, which might lead to a paradoxical therapeutic effect. It is optimal to limit the l-arg availability of tumor cells from the microenvironment while supplying l-arg for immune cells. In this study, we designed a multivesicular liposome technology to continuously supply alkaline l-arg, which simultaneously changed the acidity and l-arg deficiency in the TME, and by selectively knocking down the CAT-2 transporter, l-arg starvation of tumors was maintained while tumor-killing immune cells were enriched in the TME. The results showed that our strategy promoted the infiltration and activation of CD8+ T cells in tumor, increased the proportion of M1 macrophages, inhibited melanoma growth, and prolonged survival. In combination with anti-PD-1 antibody, our strategy reversed the low tumor response to immune checkpoint blockade therapy, showing a synergistic antitumor effect. Our work provided a reference for improving the TME combined with regulating nutritional competitiveness to achieve the sensitization of immunotherapy.

A therapeutic DC vaccine with maintained immunological activity exhibits robust anti-tumor efficacy.

Dendritic cells (DCs) vaccines are a major focus of future anti-tumor immunotherapy for their pivotal role in eliciting reactive tumor-specific T-cell responses. Tumor cell-mediated DCs (TC-DC) activation and tumor antigen-mediated DCs (TA-DC) activation are two conventional modes of DC vaccine construction in clinical studies. The former physiologically mimicks the tumor identification and rejection, significantly contributing to DC-based immune recognition and migration towards the complexed tumor microenvironment (TME). However, as immunosuppressive molecules may exist in TME, these TC-DC are generally characterized with aberrant lipid accumulation and inositol-requiring kinase 1α (IRE1α)-X-box binding protein 1 (XBP1) hyperactivation, which is provoked by overwhelming oxidative stress and endoplasmic reticulum (ER) stress, resulting in TC-DC malfunction. Oppositely, without contacting immunosuppressive TME, TA-DC vaccines perform better in T-cell priming and lymph nodes (LNs) homing, but are relatively weak in TME infiltration and identification. Herein, we prepared a KIRA6-loaded α-Tocopherol nanoemulsion (KT-NE), which simultaneously ameliorated oxidative stress and ER stress in the dysfunctional lipid-laden TC-DC. The TC-DC treated by KT-NE could maintain immunological activity, simultaneously, exhibited satisfactory chemotaxis towards LNs and tumor sites in vivo, and effectively suppressed malignant progression by unleashing activated tumor-reactive T cells. This study generated a new DC-vaccine that owned puissant aptitude to identify complicated TME as well as robust immunological activity to boost T-cell initiation, which may provide some insights into the design and application of DC-vaccines for clinical application.

ER-Targeting PDT Converts Tumors into In Situ Therapeutic Tumor Vaccines.

A therapeutic tumor vaccine is a promising approach to cancer treatment. One of its strategies is to treat patient-derived tumor cells in vitro and then administer them in vivo to induce an adaptive immune response and achieve cancer treatment. Here, we want to explore the possibility of converting cancer tissue into a therapeutic tumor vaccine through induced immunogenic cell death (ICD) in situ. We loaded indocyanine green (ICG) into liposomes (ICG-Lipo) and modified it with the pardaxin peptide to realize an endoplasmic reticulum (ER)-targeting function (Par-ICG-Lipo). A microfluidic technique was developed for loading ICG, a water-soluble molecule, into liposomes with a high encapsulation efficiency (greater than 90%). Under near-infrared (NIR) irradiation, ER-targeting photodynamic therapy (PDT) induced by Par-ICG-Lipo could promote the release of danger-signaling molecules (DAMPs) and tumor antigens (TAAs) in vivo, which significantly enhanced the immunogenicity in vivo and thus stimulates a strong antitumor immune response. This process would be further amplified by adopting dendritic cells. In general, our strategy transformed in situ tumor cells into therapeutic vaccines by ER-targeting PDT, which could provide a clinically applicable and effective approach for cancer treatment.

Optimized mobilization of MHC class I- and II- restricted immunity by dendritic cell vaccine potentiates cancer therapy.

Background: The participation of major histocompatibility complex (MHC) in antigen presentation shapes both the breadth and magnitude of specific T cell response. Dendritic cells (DCs) activated with nucleic acid or protein that encodes/incorporates multiple antigenic epitopes elicit MHC class I- and II- biased immunity, respectively. Studies demonstrate that an elevated MHC class I-directed CD8+ cytotoxicity T lymphocyte (CTL) response is able to provide survival benefits to patient with malignant tumor. However, a fully effective cancer therapy must elicit a diverse repertoire of both CD4+ and CD8+ T cell responses, raising demands on a multifaceted activation of the MHC system. Current therapeutic strategies usually lack an orchestrated mobilization of the MHC class I and II responses. Vaccines with little synergistic effect or unmanageable elicitation of the CD4+ and CD8+ T cell immunity usually fail to induce a potent and durable anti-tumor protection. Methods: Here, cationic nanoemulsions (CNEs) complexed with full-length tumor model antigen ovalbumin (OVA) in the form of mRNA or protein were constructed and used as two antigenic platforms to prepare DCs vaccines with tailored MHC participation (i.e., mRNA-DCs and protein-DCs). In exploring a vaccine regimen with optimal tumor suppressing effect, the mixing ratio of mRNA-DCs and protein-DCs was manipulated. Results: Therapeutic DCs vaccines involving both antigenic platforms induced better anti-tumor immunity in murine E.G7-OVA lymphoma model and B16-OVA melanoma model, which can be further augmented upon a meticulous reallocation of the MHC class I and II responses. Conclusion: This work indicated that a simultaneous and coordinated mobilization of the MHC-restricted immunity might potentiate cancer therapy.

Regulating immune memory and reversing tumor thermotolerance through a step-by-step starving-photothermal therapy.

BACKGROUND: Photothermal therapy (PTT) is a highly effective treatment for solid tumors and can induce long-term immune memory worked like an in situ vaccine. Nevertheless, PTT inevitably encounters photothermal resistance of tumor cells, which hinders therapeutic effect or even leads to tumor recurrence. Naïve CD8+ T cells are mainly metabolized by oxidative phosphorylation (OXPHOS), followed by aerobic glycolysis after activation. And the differentiate of effector CD8+ T cell (CD8+ Teff) into central memory CD8+ T cell (CD8+ TCM) depends on fatty acid oxidation (FAO) to meet their metabolic requirements, which is regulated by adenosine monophosphate activated protein kinase (AMPK). In addition, the tumor microenvironment (TME) is severely immunosuppressive, conferring additional protection against the host immune response mediated by PTT. METHODS: Metformin (Met) down-regulates NADH/NADPH, promotes the FAO of CD8+ T cells by activating AMPK, increases the number of CD8+ TCM, which boosts the long-term immune memory of tumor-bearing mice treated with PTT. Here, a kind of PLGA microspheres co-encapsulated hollow gold nanoshells and Met (HAuNS-Met@MS) was constructed to inhibit the tumor progress. 2-Deoxyglucose (2DG), a glycolysis inhibitor for cancer starving therapy, can cause energy loss of tumor cells, reduce the heat stress response of tumor cell, and reverse its photothermal resistance. Moreover, 2DG prevents N-glycosylation of proteins that cause endoplasmic reticulum stress (ERS), further synergistically enhance PTT-induced tumor immunogenic cell death (ICD), and improve the effect of immunotherapy. So 2DG was also introduced and optimized here to solve the metabolic competition among tumor cells and immune cells in the TME. RESULTS: We utilized mild PTT effect of HAuNS to propose an in situ vaccine strategy based on the tumor itself. By targeting the metabolism of TME with different administration strategy of 2DG and perdurable action of Met, the thermotolerance of tumor cells was reversed, more CD8+ TCMs were produced and more effective anti-tumor was presented in this study. CONCLUSION: The Step-by-Step starving-photothermal therapy could not only reverse the tumor thermotolerance, but also enhance the ICD and produce more CD8+ TCM during the treatment.

Cocktail strategy for 'cold' tumors therapy via active recruitment of CD8+ T cells and enhancing their function.

In immunotherapy, 'cold' tumors, with low T cells infiltration, hardly benefit from the treatment of immune checkpoint inhibitors (ICIs). To address this issue, we screened two 'cold' tumor models for mice with high expression of galectin-3 (Gal-3) and designed a cocktail strategy to actively recruit CD8+ T cells into the tumor microenvironment (TME), which reversed 'cold' tumors into 'hot' and remarkably elevated their ICIs-responsiveness. Gal-3, an important driving force of tumorigenesis, inhibits T cell infiltration into tumor tissue that shapes 'cold' tumor phenotype, and promotes tumor metastasis. In this respect, Gal-3 antagonist G3-C12 peptide was chosen and further loaded into poly(lactic-co-glycolic acid) (PLGA) microspheres, with the prepared G3-C12@PLGA playing a dual role of antitumor, namely, killing two birds with one stone. Specifically, G3-C12@PLGA actively recruit T cells into 'cold' tumors by rescuing IFN-γ, and simultaneously inhibit tumor metastasis induced by Gal-3. Moreover, when combined with chemotherapeutic agent (Oxaliplatin) and anti-PD-1 peptide (APP), the immunopotentiating effect of dendritic cells (DCs) was extremely improved, with T-cell depletion dramatically reversed. In vivo experiments showed that such cocktail therapy exerted remarkable antitumor effect on 'cold' breast cancer (BC) and ovarian serous cancer (OSC). These results indicated that our strategy might be promising in treating 'cold' tumors with high expression of Gal-3, which not only enhance cancer treatment outcome, but provide a new platform for the prevention of postoperative tumor recurrence/metastasis.