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Theranostics · 2020 · IF 8.579

Rationally designed dual-plasmonic gold nanorod@cuprous selenide hybrid heterostructures by regioselective overgrowth for in vivo photothermal tumor ablation in the second near-infrared biowindow

Beibei Shan,Haitao Wang,Linhu Li,Guangzhi Zhou,Yu Wen,Mingyang Chen,Ming Li

NIR-II plasmonic materials offer multiple functionalities for in vivo biomedical applications, such as photothermal tumor ablation, surface-enhanced Raman scattering biosensing, photoacoustic imaging, and drug carriers. However, integration of noble metals and plasmonic semiconductors is greatly challenging because of the large lattice-mismatch. This study reports the regioselective overgrowth of Cu 2-x Se on gold nanorods (GNRs) for preparation of dual-plasmonic GNR@Cu 2-x Se hybrid heterostructures with tunable NIR-II plasmon resonance absorption for in vivo photothermal tumor ablation. Methods: The regioselective deposition of amorphous Se and its subsequent conversion into Cu 2-x Se on the GNRs are performed by altering capping agents to produce the GNR@Cu 2-x Se heterostructures of various morphologies. Their photothermal performances for NIR-II photothermal tumor ablation are evaluated both in vitro and in vivo . Results: We find that the lateral one- and two-side deposition, conformal core-shell coating and island growth of Cu 2-x Se on the GNRs can be achieved using different capping agents. The Cu 2-x Se domain size in these hybrids can be effectively adjusted by the SeO 2 concentration, thereby tuning the NIR-II plasmon bands. A photothermal conversion efficiency up to 58-85% and superior photostability of these dual-plasmonic hybrids can be achieved under the NIR-II laser. Results also show that the photothermal conversion efficiency is dependent on the proportion of optical absorption converted into heat; however, the temperature rise is tightly related to the concentration of their constituents. The excellent NIR-II photothermal effect is further verified in the following in vitro and in vivo experiments. Conclusions: This study achieves one-side or two-side deposition, conformal core-shell coating, and island deposition of Cu 2-x Se on GNRs for GNR@Cu 2-x Se heterostructures with NIR-II plasmonic absorption, and further demonstrates their excellent NIR-II photothermal tumor ablation in vivo . This study provides a promising strategy for the rational design of NIR-II dual-plasmonic heterostructures and highlights their therapeutic in vivo potential.

CAS / MDL: 112-02-7 57-09-0
研究领域: 材料科学 · 生物医学工程 · 纳米技术 · 癌症治疗
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MATERIALS & DESIGN · 2023 · IF 8.4

Designing Nd-doped bismuth selenide nanosheets with boosted photothermal conversion for imaging guided cancer therapy

Yanbang Lian,Congcong Wang,Yu Meng,Junqiang Dong,Jianbin Zhang,Gongxun Bai,Jianbo Gao

Rational design and preparation of multifunctional low dimensional nanomaterials are of great importance for in vivo imaging and safety therapy. Meanwhile, nanomaterials with good bio-compatible and effectively photothermal conversion are still demanded to be fabricated in biomedicine. In this work, we have developed two-dimensional bismuth selenide nanosheets as the imaging and photothermal nanoagents. Through doping engineering, the near infrared photothermal conversion of Nd doped nanosheets was boosted by 52 %, which is higher than many previous works. Besides, the prepared nanomaterials can realize infrared and in vivo computed X-ray tomography bioimaging, due to the rich optical-magnetic properties of Nd atoms. The in vitro and vivo experiments with mice display that the Nd doped nanosheets have low toxicity and high biocompatibility. More importantly, the nanomaterials can efficiently achieve photothermal tumor ablation. It is suggested that designed and developed nanosheets have promising applications for biomedicine.

研究领域: 纳米技术 · 生物医学工程 · 材料科学 · 癌症治疗 · 成像技术
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ACS Omega · 2023 · IF 4.1

Selenide Heterostructure Nanosheets with Efficient Near-Infrared Photothermal Conversion for Therapy

Yanbang Lian,Congcong Wang,Yu Meng,Junqiang Dong,Jianbin Zhang,Shiqing Xu,Gongxun Bai,Jianbo Gao

Photothermal therapy has been regarded as one of promising ways for tumor treatment. However, nanoagents with highly efficient thermal conversion and good bio-compatibility are still needed to be developed in biomedicine. In this work, we prepared two-dimensional heterostructures with bismuth selenide and tungsten selenide nanosheets as photothermal nanoagents. Near-infrared photothermal conversion of selenide heterostructure nanosheets can reach up to 40.75% under 808 nm excitation. It is known that selenium is a critical element to human health. More importantly, our experiments with mice show that the heterostructure nanosheets have low toxicity and high biocompatibility both in vitro and in vivo. The nanoagents based on heterostructures can effectively realize photothermal tumor ablation. It is suggested that the developed selenide nanosheets have great potential application in cancer therapy.

研究领域: 纳米技术 · 生物医学工程 · 材料科学 · 癌症研究
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Bioactive Materials · 2021 · IF 14.593

2D antimonene-integrated composite nanomedicine for augmented low-temperature photonic tumor hyperthermia by reversing cell thermoresistance

Jianrong Wu,Xiaojun Cai,Gareth R. Williams,Zheying Meng,Weijuan Zou,Li Yao,Bing Hu,Yu Chen,Yuanyi Zheng

The overexpression of heat shock proteins (HSPs) in tumor cells can activate inherent defense mechanisms during hyperthermia-based treatments, inducing thermoresistance and thus diminishing the treatment efficacy. Here, we report a distinct “non-inhibitor involvement” strategy to address this issue through engineering a calcium-based nanocatalyst (G/ [email protected] 3 -PEG). The constructed nanocatalyst consists of calcium carbonate (CaCO 3 )-supported glucose oxidase (GOD) and 2D antimonene quantum dots (AQDs), with further surface modification by lipid bilayers and polyethylene glycol (PEG). The engineered G/ [email protected] 3 -PEG nanocatalyst features prolonged blood circulation, which is stable at neutral pH but rapidly degrades under mildly acidic tumor microenvironment, resulting in rapid release of drug cargo in the tumor microenvironment. The integrated GOD effectively catalyzes the depletion of glucose for reducing the supplies of adenosine triphosphate (ATP) and subsequent down-regulation of HSP expression. This effect then augments the therapeutic efficacy of photothermal hyperthermia induced by 2D AQDs upon irradiation with near-infrared light as assisted by reversing the cancer cells’ thermoresistance. Consequently, synergistic antineoplastic effects can be achieved via low-temperature photothermal therapy. Systematic in vitro and in vivo evaluations have demonstrated that G/ [email protected] 3 -PEG nanocatalysts feature potent antitumor activity with a high tumor-inhibition rate (83.92%). This work thus paves an effective way for augmenting the hyperthermia-based tumor treatments via restriction of the ATP supply.

研究领域: 纳米医学 · 癌症治疗 · 材料科学 · 生物医学工程
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ACS Applied Materials & Interfaces · 2020 · IF 8.758

Reshaping Tumor Immune Microenvironment through Acidity-Responsive Nanoparticles Featured with CRISPR/Cas9-Mediated Programmed Death-Ligand 1 Attenuation and Chemotherapeutics-Induced Immunogenic Cell Death

Kun Tu,Huan Deng,Li Kong,Yi Wang,Ting Yang,Qian Hu,Mei Hu,Conglian Yang,Zhiping Zhang

Blocking immune checkpoints with monoclonal antibody has been verified to achieve potential clinical successes for cancer immunotherapy. However, its application has been impeded by the “cold” tumor microenvironment. Here, weak acidity-responsive nanoparticles co-loaded with CRISPR/Cas9 and paclitaxel (PTX) with the ability to convert “cold” tumor into “hot” tumor are reported. The nanoparticles exhibited high cargo packaging capacity, superior transfection efficiency, well biocompatibility, and effective tumor accumulation. The CRISPR/Cas9 encapsulated in nanoparticles could specifically knock out cyclin-dependent kinase 5 gene to significantly attenuate the expression of programmed death-ligand 1 on tumor cells. More importantly, PTX co-delivered in nanoparticles could significantly induce immunogenic cell death, reduce regulatory T lymphocytes, repolarize tumor-associated macrophages, and enhance antitumor immunity. Therefore, the nanoparticles could effectively convert cold tumor into hot tumor, achieve effective tumor growth inhibition, and prolong overall survival from 16 to 36 days. This research provided a referable strategy for the development of combinatorial immunotherapy and chemotherapy.

CAS / MDL: 25952-53-8 6066-82-6
研究领域: 癌症免疫治疗 · 纳米技术 · 基因编辑 · 肿瘤学
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Pharmaceutics · 2021 ·Vol. 13 ·期 7 ·984 · IF 6.321

Novel PVA-Based Microspheres Co-Loaded with Photothermal Transforming Agent and Chemotherapeutic for Colorectal Cancer Treatment

Yao Zhang,Zirui He,Fan Yang,Changqing Ye,Xia Xu,Shige Wang,Ling Zhang,Duowu Zou

Background: We previously designed an electrospinning chitosan (CS) nanofiber-based carrier, using polyvinyl alcohol (PVA) as an adjuvant to deliver doxorubicin (DOX) and MoS2nanosheets for postoperative tumor re-occurrence inhibition. However, owing to that the nanofibrous mat is un-injectable, this composite nanofiber is far from being clinically applicable. Materials and Methods: Via modulating the electrospray parameters, polyvinyl alcohol (PVA) beads string doped with DOX and MoS2(PVA/MoS2/DOX microspheres) were prepared, which were further crosslinked with glutaraldehyde to obtain the water-stability. Results: Under the 808-nm laser irradiation, MoS2nanosheets rendered the prepared PVA/MoS2/DOX microspheres an excellent light-to-heat conversion performance with η of 23.2%. Besides, the heat generated by near-infrared laser irradiation can improve the effect of chemotherapy by promoting the release rate of DOX. HT29 cell and tumor-bearing nude mice were used to systematically study the combined tumor treatment efficiency of composite nanospheres. Conclusion: PVA/MoS2/DOX nanospheres have excellent photothermal effect and chemotherapy effect, which can completely suppress the tumor recurrence. Therefore, the PVA/MoS2/DOX nanospheres are anticipated to find potential applications in the treatment of local colorectal cancer.Keywords:electrospinning;nanospheres;chemotherapy;photothermal tumor therapy;colorectal cancer

CAS / MDL: 9002-89-5
研究领域: 药学 · 生物医学工程 · 肿瘤学
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Matter · 2022 · IF 19.967

Transforming “cold” tumors into “hot” ones via tumor-microenvironment-responsive siRNA micelleplexes for enhanced immunotherapy

Yunfei Yi,Mian Yu,Chan Feng,Huisong Hao,Weiwei Zeng,Chuchu Lin,Hongzhong Chen,Feng Lv,Dunwan Zhu,Xiaoyuan Ji,Lin Mei,Meiying Wu,Wei Tao

Summary It is highly desirable to turn “cold” tumors into “hot” ones to improve the efficacy of antitumor immunotherapy. Herein, we develop the peptide-based small interfering RNA (siRNA) micelleplexes (P A7R @siPD-L1) for normalizing vascular-immune crosstalk to establish a positive feedback loop in potentiating antitumor immunotherapy. These micelleplexes are equipped with tumor-microenvironment-responsive property for precise drug delivery and release. The prepared P A7R @siPD-L1-mediated photodynamic therapy could eliminate solid tumors and trigger immunogenic cell death to generate systematic immune responses. Meanwhile, the antiangiogenic peptide A7R normalizes the tumor vasculature by converting chaotic vascular systems into matured and organized ones, thus alleviating tumor hypoxia and promoting intratumoral infiltration by immune cells. Antitumor immunogenicity would be further strengthened with the aid of siPD-L1 by muting the resistance of tumor cells against immune effector cells. This study provides a unique therapeutic strategy in turning “cold” tumors into “hot” tumors enabled by siRNA nanomaterial .

研究领域: 肿瘤学 · 免疫疗法 · 纳米医学 · 癌症生物学
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ACS Applied Materials & Interfaces · 2021 · IF 9.229

Reinforcing the Combinational Immuno-Oncotherapy of Switching “Cold” Tumor to “Hot” by Responsive Penetrating Nanogels

Qingle Song,Guofang Zhang,Bo Wang,Guoli Cao,Dongjie Li,Yu Wang,Yuqian Zhang,Jin Geng,Hongchang Li,Yang Li

Although immuno-oncotherapy in clinic has gained great success, the immunosuppressive tumor microenvironment (TME) existing in the “cold” tumor with insufficient and exhausted lymphocytes may result in a lower-than-expected therapeutic efficiency. Therefore, a properly designed synergistic strategy that can effectively turn the “cold” tumor to “hot” should be considered to improve the therapeutic effects of immuno-oncotherapy. Herein, TME-responsive penetrating nanogels (NGs) were developed, which can improve the delivery and penetration of the co-loaded resiquimod (R848) and green tea catechin (EGCG) in tumors by a nano-sized controlled releasing system of the soluble cyclodextrin-drug inclusion complex. Consequently, the NGs effectively promoted the maturation of dendritic cells, stimulated the cytotoxic T lymphocytes (CTLs), and decreased the PD-L1 expression in tumors. The combination of NGs with the OX40 agonist (αOX40) further synergistically enhanced the activation and infiltration of CTLs into the deep tumor and inhibited the suppression effects from the regulatory T cells (Tregs). As a result, an increased ratio of active CTLs to Tregs in tumors (20.66-fold) was achieved with a 91.56% tumor suppression effect, indicating a successful switch of “cold” tumors to “hot” for an immunologically beneficial TME with significantly improved anti-tumor immune therapeutics. This strategy could be tailored to other immuno-oncotherapeutic approaches to solve the urgent efficiency concerns of the checkpoint-based treatment in clinic.

研究领域: 肿瘤学 · 免疫学 · 纳米医学 · 药学
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Bioactive Materials · 2024 · IF 18

NIR-II photo-accelerated polymer nanoparticles boost tumor immunotherapy via PD-L1 silencing and immunogenic cell death

Tian Zhang,Dongsheng Tang,Pengfei Wu,Shaoping Jiang,Yuquan Zhang,Abid Naeem,Yong Li,Chunhui Li,Bo Hu,Shuai Guo,Caixia Sun,Haihua Xiao,Ran Yan,Yuhua Weng,Yuanyu Huang

Immune checkpoint blockade (ICB) therapy is a widely favored anti-tumor treatment, but it shows limited response to non-immunogenic “cold” tumors and suffers from drug resistance. Photodynamic therapy (PDT), as a powerful localized treatment approach, can convert a “cold tumor” into a “hot tumor” by inducing immunogenic cell death (ICD) in tumor cells, thereby enhancing tumor immunogenicity and promoting tumor immunotherapy. However, the effectiveness of PDT is largely hindered by the limited penetration depth into tumor tissues. To address these issues, we proposed an all-in-one drug system with NIR-II photo-accelerated PDT effects, efficient immune checkpoint gene silencing, and a facile manufacturing process. The so-called all-in-one drug system comprises a multi-modal designed polymer PPNP and siRNA. PPNP is an amphipathic polymer that includes the near infrared-II (NIR-II) photosensitizer Aza-boron-dipyrromethene (Aza-BODIPY), a glutathione (GSH)-cleavable linker, and a cationic monomer derived from cholesterol. PPNP can self-assemble and efficiently load siRNA. Under laser irradiation, PPNP triggers a potent ICD cascade, causing the on-demand release of siPD-L1, reshaping the tumor's immunosuppressive microenvironment, effectively inhibiting the growth of various tumors, and stimulating the immune memory. This study represents a generalized platform for PDT and gene silencing, designed to modulate immune-related signaling pathways for improved anticancer therapy.

研究领域: 肿瘤学 · 免疫治疗 · 药理学 · 生物医学工程 · 纳米技术
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