Gaoli Niu’s research while affiliated with Tianjin University and other places

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Publications (13)


Schematic illustration of NIR‐II photoimmunotherapy and photoacoustic imaging for orthotopic ovarian cancer using SKCN‐based nanoparticles. A) Synthesis of the SKCN molecule. B) Preparation of FA‐SRNPs by encapsulating SKCN and R848 with three different PEGs. C) Photoacoustic imaging of the PA1064 channel and 1064 nm laser‐triggered photoimmunotherapy targeting primary and metastatic tumors.
Comparison of SKCN and Y6, along with the characterization of SKCN and nanoparticles. A) Molecular structure comparison of SKCN and Y6. B) TD‐DFT calculated molecular orbitals and energy diagrams at the B3LYP/6‐31G(d) level. OH/L represents overlap integral between HOMO and LUMO. (HOMO: orange, LUMO: blue). C) Simulated Jablonski diagram. D) Energy level diagram of SKCN and Y6 derived from the electrochemical cyclic voltammetry. Molecular structures and theoretical density distribution for the frontier molecular orbits of HOMO and LUMO for SKCN and E) and Y6 F), calculated using DFT method. G) UV‒vis absorption spectra of SKCN in different states. H) TEM images of FA‐SNPs and FA‐SRNPs. Scale bar = 100 µm. I) Zeta potential of FA‐SNPs and FA‐SRNPs. J) Particle size distributions of FA‐SNPs and FA‐SRNPs. K) TEM images of FA‐SRNPs after incubation with GSH. Scale bar = 100 µm. L) Zeta potential changes of FA‐SRNPs over time after incubation with GSH.
Evaluation of FA‐SNPs PTT and PDT effects and photothermal conversion efficiency (η). Temperature changes of FA‐SNPs solutions at different concentrations under 1064 nm laser irradiation at 1.0 W cm⁻² A) and infrared thermal imaging B). temperature changes of FA‐SNPs solutions under different laser powers at the same concentration C) and infrared thermal imaging D). E) Five cycles of heating and cooling curves of FA‐SNPs solutions with the 1064 nm laser on‐off. F) UV‒vis absorption spectra of FA‐SNPs under different high‐temperature conditions. G) Heating and cooling curves of FA‐SNPs solutions under 1064 nm laser irradiation. H) Linear relationship between the cooling time and ‐lnθ with a calculated photothermal conversion efficiency (η) of 75.14%. DPBF absorption peak changes at 420 nm under 1064 nm laser irradiation for different concentrations of FA‐SNPs solutions (I) and after irradiation at different powers J). The ABDA absorption peak changes at 400 nm for different concentrations of FA‐SNPs solutions under 1064 nm laser irradiation K) and after irradiation at different powers L).
In vivo antitumor effects. A) Effects of different concentrations of FA‐SNPs on ID8 cell viability (n = 5). B) Effects of different powers of 1064 nm laser irradiation with varying concentrations of FA‐SNPs on ID8 cell viability (n = 5). C) Effects of different concentrations of R848 on cell viability (n = 5). D) CLSM images showing the cellular uptake of m‐THPP‐labeled SNPs and FA‐SNPs in ID8 cells at different time points; scale bar = 50 µm. E) FCM analysis of ROS generation in ID8 cells subjected to different treatments. F) Fluorescence microscopy images showing ROS generation in ID8 cells under different treatments. Scale bar = 200 µm. G) CLSM images showing changes in the mitochondrial membrane potential of ID8 cells stained with JC‐1 after different treatments. Scale bar = 50 µm. H) CLSM images showing DNA damage in ID8 cells marked by 𝛾‐H2AX under different treatments; scale bar = 50 µm. I) Merged fluorescence microscopy images of live/dead cell staining in different treatment groups; scale bar = 200 µm. J) FCM analysis of apoptosis in ID8 cells subjected to different treatments. K) Western blot images showing the expression of apoptotic proteins Bcl‐2 and Bax.
Analysis of induced ICD and the in vitro immune response. Representative CLSM images of CRT exposure (A, scale bar = 50 µm) and HMGB1 expression (B, scale bar = 100 µm) in cells subjected to different treatments. C) Schematic of the Transwell system. FCM analysis of DC maturation D) and quantitative analysis G) in different treatment groups. FCM analysis of macrophages E) with quantitative analysis of M1 (H) and M2 (I) phenotypes and FCM analysis of CTLs F) with quantitative analysis J) across different treatment groups. The data are presented as the means ± SDs. The p‐values were calculated via one‐way analysis of variance (ANOVA), *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001.

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Quinoidal Semiconductor Nanoparticles for NIR‐II Photoacoustic Imaging and Photoimmunotherapy of Cancer
  • Article
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December 2024

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51 Reads

Gaoli Niu

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Guangkun Song

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Photoagents with ultra‐high near‐infrared II (NIR‐II) light energy conversion efficiency hold great promise in tumor phototherapy due to their ability to penetrate deeper tissues and minimize damage to surrounding healthy cells. However, the development of NIR‐II photoagents remain challenging. In this study, an all‐fused‐ring quinoidal acceptor‐donor‐acceptor (A‐D‐A) molecule, SKCN, with a BTP core is synthesized, and nanoparticles named FA‐SNPs are prepared. The unique quinoidal structure enhances π‐electron delocalization and bond length uniformity, significantly reducing the bandgap of SKCN, resulting in strong NIR‐II absorption, a high molar extinction coefficient, and a photothermal conversion efficiency of 75.14%. Enhanced molecular rigidity also facilitates efficient energy transfer to oxygen, boosting reactive oxygen species generation. By incorporating the immunomodulator R848, FA‐SRNPs nanoparticles are further developed, effectively modulating the tumor immune microenvironment by reducing Tregs and M‐MDSCs infiltration, promoting dendritic cell maturation, M1 macrophage polarization, and activating CD8+ T cells and NK cells. Comprehensive studies using orthotopic ovarian cancer models demonstrated strong tumor targeting, photoacoustic imaging capabilities, and significant tumor suppression and metastasis inhibition, and also showing excellent therapeutic efficacy in an orthotopic breast cancer model. This study provides strong evidence for the potential application of quinoidal A‐D‐A molecules in cancer photoimmunotherapy.

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Several clinical trials are currently underway to this investigate
Several clinical trials are currently underway to this investigate (continued)
Research progress of immune checkpoint inhibitors in ovarian cancer

December 2024

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12 Reads

Exploration of Immunology

Ovarian cancer is the deadliest malignant tumor in the female reproductive system. Despite advancements in standard treatments such as tumor debulking surgery and platinum-based chemotherapy, the overall survival rate remains low. The emergence of targeted therapies, including Poly(ADP-ribose) polymerase (PARP) inhibitors and anti-angiogenic agents, has provided new avenues for treatment. However, drug resistance and disease heterogeneity continue to pose significant challenges. Immune checkpoint inhibitors (ICIs), as an emerging therapeutic approach, primarily target the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathways to restore anti-tumor immune responses. Although ICIs have shown significant efficacy in other malignancies, their effectiveness in ovarian cancer is limited, with a response rate of only 10–15% for monotherapy. Recent studies have focused on combining ICIs with chemotherapy, anti-angiogenic agents, or PARP inhibitors to enhance therapeutic outcomes. This article reviews the progress of ICIs in ovarian cancer, including monotherapy and combination treatment strategies, and explores emerging therapeutic targets and strategies aimed at improving patient prognosis and achieving personalized treatment. By gaining a deeper understanding of the tumor microenvironment and its immune evasion mechanisms, there is hope for developing more effective treatment options in the future, ultimately improving the survival rates and quality of life for ovarian cancer patients.


Biomimetic Dual‐Driven Heterojunction Nanomotors for Targeted Catalytic Immunotherapy of Glioblastoma

November 2024

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55 Reads

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2 Citations

The existence of the blood–brain barrier (BBB) and the characteristics of the immunosuppressive microenvironment in glioblastoma (GBM) present significant challenges for targeted GBM therapy. To address this, a biomimetic hybrid cell membrane‐modified dual‐driven heterojunction nanomotor (HM@MnO2‐AuNR‐SiO2) is proposed for targeted GBM treatment. These nanomotors are designed to bypass the BBB and target glioma regions by mimicking the surface characteristics of GBM and macrophage membranes. More importantly, the MnO2‐AuNR‐SiO2 heterojunction structure enables dual‐driven propulsion through near‐infrared‐II (NIR‐II) light and oxygen bubbles, allowing effective treatment at deep tumor sites. Meanwhile, the plasmonic AuNR‐MnO2 heterostructure facilitates the separation of electron–hole pairs and generates reactive oxygen species (ROS), inducing immunogenic tumor cell death under NIR‐II laser irradiation. Furthermore, MnO2 in the tumor microenvironment reacts to release Mn²⁺ ions, activating the cGAS‐STING pathway and enhancing antitumor immunity. In vitro and in vivo experiments demonstrate that these dual‐driven biomimetic nanomotors achieve active targeting and deep tumor infiltration, promoting M1 macrophage polarization, dendritic cell maturation, and effector T‐cell activation, thereby enhancing GBM catalysis and immunotherapy through ROS production and STING pathway activation.


A Programmable Oral Nanomotor Microcapsule for the Treatment of Inflammatory Bowel Disease

November 2024

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72 Reads

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4 Citations

Given the unique anatomy and location of inflammatory bowel disease (IBD), oral pharmacological treatment is the mainstay for managing IBD because of its convenience and direct accessibility to the gastrointestinal tract. However, efficient delivery systems must be designed to navigate the harsh gastrointestinal environment during application. Here, an innovative oral drug delivery system was proposed using nanomotor (NM)‐loaded soluble microcapsules for treating IBD. MnO2‐Au‐mSiO2 NMs incorporate partially encapsulated MnO2 antennas that convert reactive oxygen species into oxygen, autonomously propelling the NMs. Astaxanthin (AST), known for its anti‐inflammatory properties, is loaded into the mesoporous silica (mSiO2) of NMs (AST@NMs). AST effectively reduces inflammation and shifts macrophages from a proinflammatory (M1) phenotype to an anti‐inflammatory (M2) phenotype. To protect the nanomotors from harsh digestive conditions and achieve intestinal‐responsive release, using photocurable 3D printing, we fabricated enteric‐coated oral microcapsules (MCs). Additionally, to prevent leakage of AST@NMs, a calcium alginate shell was cured in situ on the surface of the microcapsules (AST@NMs@MCs). In vitro and in vivo, AST@NMs@MCs effectively reduced inflammation, repaired the intestinal barrier, and modulated the gut microbiota. These findings underscore the protective effects of the microcapsules on AST@NM, highlighting their potential as a promising strategy for treating colitis.


An Acceptor–Donor–Acceptor Structured Nano‐Aggregate for NIR‐Triggered Interventional Photoimmunotherapy of Cervical Cancer

August 2024

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58 Reads

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6 Citations

Compared with conventional therapies, photoimmunotherapy offers precise targeted cancer treatment with minimal damage to healthy tissues and reduced side effects, but its efficacy may be limited by shallow light penetration and the potential for tumor resistance. Here, an acceptor–donor‐acceptor (A‐D‐A)‐structured nanoaggregate is developed with dual phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), triggered by single near‐infrared (NIR) light. Benefiting from strong intramolecular charge transfer (ICT), the A–D–A‐structured nanoaggregates exhibit broad absorption extending to the NIR region and effectively suppressed fluorescence, which enables deep penetration and efficient photothermal conversion (η = 67.94%). A suitable HOMO–LUMO distribution facilitates sufficient intersystem crossing (ISC) to convert ground‐state oxygen (³O2) to singlet oxygen (¹O2) and superoxide anions (·O2⁻), and catalyze hydroxyl radical (·OH) generation. The enhanced ICT and ISC effects endow the A–D–A structured nanoaggregates with efficient PTT and PDT for cervical cancer, inducing efficient immunogenic cell death. In combination with clinical aluminum adjuvant gel, a novel photoimmunotherapy strategy for cervical cancer is developed and demonstrated to significantly inhibit primary and metastatic tumors in orthotopic and intraperitoneal metastasis cervical cancer animal models. The noninvasive therapy strategy offers new insights for clinical early‐stage and advanced cervical cancer treatment.


Oral Heterojunction Coupling Interventional Optical Fiber Mediates Synergistic Therapy for Orthotopic Rectal Cancer

June 2024

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35 Reads

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3 Citations

Catalytic therapy has shown great potential for clinical application. However, conventional catalytic therapies rely on reactive oxygen species (ROS) as “therapeutic drugs,” which have limitations in effectively inhibiting tumor recurrence and metastasis. Here, a biomimetic heterojunction catalyst is developed that can actively target orthotopic rectal cancer after oral administration. The heterojunction catalyst is composed of quatrefoil star‐shaped BiVO4 (BVO) and ZnIn2S4 (ZIS) nanosheets through an in situ direct growth technique. Poly‐norepinephrine and macrophage membrane coatings afford the biomimetic heterojunction catalyst (BVO/ZIS@M), which has high rectal cancer targeting and retention abilities. The coupled optical fiber intervention technology activates the multicenter coordination of five catalytic reactions of heterojunction catalysts, including two reduction reactions (O2→·O2⁻ and CO2→CO) and three oxidation reactions (H2O→·OH, GSH→GSSG, and LA→PA). These catalytic reactions not only induce immunogenic death in tumor cells through the efficient generation of ROS/CO and the consumption of GSH but also specifically lead to the use of lactic acid (LA) as an electron donor to improve catalytic activity and disrupt the LA‐mediated immunosuppressive microenvironment, mediating synergistic catalysis and immunotherapy for orthotopic rectal cancer. Therefore, this optical fiber intervention triggered the combination of heterojunction catalytic therapy and immunotherapy, which exhibits prominent antitumor effects.



Biomimetic piezoelectric nanomaterial-modified oral microrobots for targeted catalytic and immunotherapy of colorectal cancer

May 2024

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51 Reads

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20 Citations

Science Advances

Lactic acid (LA) accumulation in the tumor microenvironment poses notable challenges to effective tumor immunotherapy. Here, an intelligent tumor treatment microrobot based on the unique physiological structure and metabolic characteristics of Veillonella atypica (VA) is proposed by loading Staphylococcus aureus cell membrane–coating BaTiO 3 nanocubes (SAM@BTO) on the surface of VA cells (VA-SAM@BTO) via click chemical reaction. Following oral administration, VA-SAM@BTO accurately targeted orthotopic colorectal cancer through inflammatory targeting of SAM and hypoxic targeting of VA. Under in vitro ultrasonic stimulation, BTO catalyzed two reduction reactions (O 2 → •O 2 ⁻ and CO 2 → CO) and three oxidation reactions (H 2 O → •OH, GSH → GSSG, and LA → PA) simultaneously, effectively inducing immunogenic death of tumor cells. BTO catalyzed the oxidative coupling of VA cells metabolized LA, effectively disrupting the immunosuppressive microenvironment, improving dendritic cell maturation and macrophage M1 polarization, and increasing effector T cell proportions while decreasing regulatory T cell numbers, which facilitates synergetic catalysis and immunotherapy.



Figure 2. Comparison of imaging data before and after anlotinib combined with penpulimab in the treatment of recurrent lung and brain metastases. The lesions in the same sites disappeared after treatment. Cranial and chest CT scans (A & E) before treatment and (B & F) 6 months, (C & G) 9 months and (D & H) 15 months after treatment.
Figure 3. Vaginal albuginea-like changes and intravaginal purulent inflammatory changes. (A) Vaginal albuginea-like changes and intravaginal purulent inflammatory changes (3 May 2022). (B) Inflammatory lesions in the vagina have subsided (20 June 2022). (C) MRI showed inflammatory purulent lesions in the bladder and vagina. (D & E) Hematoxylin and eosin staining results of histopathological sections in the vagina. (F) 1 February 2023: MRI showed no signs of recurrence.
Figure 4. The changes in squamous cell carcinoma antigen levels during treatment.
Penpulimab and Anlotinib in an Elderly Patient with Recurrent Cervical Cancer: A Case Report and Literature Review

June 2023

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14 Reads

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2 Citations

We present a case of a 76-year-old patient with recurrent cervical cancer who underwent first-line treatment with penpulimab combined with anlotinib. The patient was diagnosed with poorly differentiated stage III C1r cervical squamous cell carcinoma and received standard cisplatin-sensitized chemoradiotherapy, subsequently achieving a good treatment effect of complete response. Recurrence occurred nearly 14 months after treatment, with multiple metastases including in the brain and lung. Oral anlotinib was less effective, but the treatment of penpulimab combined with anlotinib showed an obvious curative effect. It has been maintained for more than 17 months, and as of April 2023 the patient is still maintaining her response. Our case suggests that penpulimab combined with anlotinib has promising efficacy in the treatment of elderly patients with recurrent cervical cancer.


Citations (7)


... [1,12,13] In NFA-like PSs that commonly adopting A-D-A conjugated frameworks, the planar and fused-ring donor-cores are essential to render their absorption to NIR region for enhancing tissue penetration and treatment safety. [14,15] Hence, the five-tonine fused-ring skeletons are generally utilized in ITIC-or Y6like PSs. [16][17][18][19] However, the planar molecular configurations of NFA-like PSs make intermolecularstacking severely and give rise to aggregation-caused fluorescence quenching effect. ...

Reference:

A Spiro‐Based NIR‐II Photosensitizer with Efficient ROS Generation and Thermal Conversion Performances for Imaging‐Guided Tumor Theranostics
An Acceptor–Donor–Acceptor Structured Nano‐Aggregate for NIR‐Triggered Interventional Photoimmunotherapy of Cervical Cancer

... In vivo results proved the system efficacy as an amplifier of radiotherapy-induced replicative stress, leading to increased DNA damage and reduced tumor hypoxic via HIF-1α downregulation, culminating in tumor volume reduction [117]. Recently, Li et al. developed a catalytic therapy employing a quatrefoil-shaped heterojunction catalyst coated with poly-norepinephrine and macrophage membranes (BVO/ZIS@M) capable of using lactic acid as an electron donor [118]. Furthermore, this platform exhibits an intrinsic ability to oxidize glutathione and increase ROS levels within the tumor, namely superoxide (O 2 − ) and hydroxyl radical (·OH), as well as carbon monoxide (CO) after optical fiber intervention, causing DNA or mitochondria membrane damage, and drastically increasing the percentage of tumor cells undergoing apoptosis (Fig. 6). ...

Oral Heterojunction Coupling Interventional Optical Fiber Mediates Synergistic Therapy for Orthotopic Rectal Cancer

... These mature DCs migrate to the lymph nodes, where they present the captured TAAs to T cells, thereby activating effector T cells. Effector T cells exit the lymph nodes, enter the circulatory system, and infiltrate TME [23,24]. They specifically recognize and bind to tumor cells through the interaction of the T cell receptor (TCR) with major histocompatibility complex (MHC) I molecules, directly killing tumor cells by releasing perforin and granzyme, or inducing tumor cell apoptosis through the regulation of the Fas/FasL pathway ( Figure 2) [25,26]. ...

Nanotechnology-based in situ cancer vaccines: Mechanisms, design, and recent advances
  • Citing Article
  • June 2024

Nano Today

... Nonetheless, the challenges of bacterial survival within the intestinal milieu necessitate strategies like encapsulation to enhance their viability. An alternative avenue involves harnessing beneficial microorganisms native to the human microbiota, genetically engineering them, and deploying them for the treatment of intestinal inflammatory diseases or colorectal cancer, ensuring prolonged survival within the gut environment (Russell et al. 2022;Fan et al. 2024). Moreover, the heterogeneity of the intestinal milieu poses a significant challenge. ...

Biomimetic piezoelectric nanomaterial-modified oral microrobots for targeted catalytic and immunotherapy of colorectal cancer
  • Citing Article
  • May 2024

Science Advances

... Another approach that might expedite the production process is investigating biofabrication methods that use biological systems such as bacterial or yeast-based systems to construct components. 327 5.4. Delivery and Targeting. ...

Intelligent micro/nanomotors: Fabrication, propulsion, and biomedical applications
  • Citing Article
  • April 2024

Nano Today

... This regimen showed good efficacy and acceptable safety as a second-line or subsequent treatment for advanced cervical cancer patients [30]. Additionally, Gaoli Ni et al. reported a case of a patient with advanced cervical cancer with multiple metastases post-radiotherapy and chemotherapy, who achieved complete tumor remission using the same treatment protocol [31]. ...

Penpulimab and Anlotinib in an Elderly Patient with Recurrent Cervical Cancer: A Case Report and Literature Review

... Although lymph node involvement in paraaortic site deteriorated the outcomes of cervical cancer patients, the benefit of para-aortic lymph nodes dissection needed further validation (Cho et al. 2020). Owing to the potential complications of lymph node resection, SLN biopsy or selective lymph node dissection was possibly considered as one of the standard therapies for early cervical cancer (Chiyoda et al. 2022;Niu et al. 2022;Poddar and Maheshwari 2021). Consequently, understanding the pattern of LNM contributed to performing lymph node related surgery. ...

Association Study between the Sentinel Lymph Node Biopsy and the Clinicopathological Features of Patients with Cervical Cancer

Disease Markers