ACS Omega
·
2019
·
IF 2.584
Jiang Ni,Ying Sun,Jinfang Song,Yiqing Zhao,Qiufang Gao,Xia Li
Recent studies have identified photodynamic therapy (PDT) as a promising approach for cancer treatment. Here, in this study, we have constructed cancer cell membrane (CCM)-coated silica nanoparticles (SIL) as an artificial cell carrier (CCM/SIL) to effectively deliver chlorin e6 (Ce6), a commonly adopted photodynamic reagent (CCM/SIL/Ce6), to achieve enhanced PDT of cancer. In addition, apart from the generally recognized cytotoxicity induced by reactive oxygen species (ROS), our study also revealed that ROS could further potentiate the loss of intercellular junctions and integrity disruption as a result of down-regulation of VE-cadherin and CD31. Consequently, dendritic cells (DCs) were more readily accumulated to the tumor tissue and became maturated, which secreted tumor necrosis factor-α and interleukin-12 (IL-12) to trigger the following immune responses. Our work not only explored the anticancer feasibility of a new system but also demonstrated the underlining mechanisms responsible for PDT-induced anticancer effects, which offers a new perspective to employ and improve the efficacy of PDT and related systems.
研究领域:
肿瘤学
·
纳米技术
·
免疫治疗
·
光动力疗法
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Therapeutics
·
2024
·
IF 3.7
Lida Feng,Guixiao Huang,Qifang Lei,Mingkang Liang,Dashi Deng,Xiaocen Liu,Chenfan Kong,Chenchen Li,Xiyang Tan,Guangzhi Li,Song Wu
Intravesical instillation-based immunotherapy for bladder-preservation of bladder cancer (BCa) treatment has not been explored. In the current study, two irrigated nano-formulations of immunological adjuvant-fluorinated chitosan (FCS) and therapeutic antibody-FCS are developed for synergistic immunotherapy against BCa. In this system, FCS is employed as a transepithelial carrier to assemble with bovine serum albumin (BSA)-flubendazole (FBZ) complex and anti-PD-1 (αPD-1) respectively, to facilitate efficient transepithelial delivery of intravesical FBZ-BSA and αPD-1 though transiently regulating the distribution of tight junction proteins on bladder epithelium. In addition, the FBZ–BSA complex exhibits tumor microenvironment-responsive charge reversal and BSA carrier-broken effects to drive tumor-targeted dissociation and drug release of FBZ–BSA/FCS. Moreover, FBZ not only promotes apoptosis and inhibits glycolysis in cancer cells but also displays adjuvant properties to activate potent immune responses through IL-12/IFN-γ pathway. Interestingly, combined perfusion of FBZ–BSA/FCS and αPD-1/FCS nano-formulations can significantly activate the tumor immune microenvironment, especially CD8 + T cell infiltration and αPD-1 sensitivity, and finally remarkably inhibit tumor growth in the mouse orthotopic BCa model. Thus, this study presents a novel intravesical delivery platform for ICB antibodies and a smart adjuvant system to achieve potent synergy immunotherapy, which is promising for bladder-preserving treatment against BCa.
研究领域:
药学
·
癌症研究
·
免疫学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-21
·
IF 10.6
Chen Shang,He Yan,Huang Xin,Shen Yao,Zou Qingshuang,Yang Gun,Fu Li,Liu Quan,Luo Dixian
Tumor-associated macrophages (TAMs) are a promising target for cancer immunotherapy, but delivering therapeutic agents to TAMs within the tumor microenvironment (TME) is challenging. In this study, a photosensitive, dual-targeting nanoparticle system (M.RGD@Cr-CTS-siYTHDF1 NPs) was developed. The structure includes a shell of DSPE-modified RGD peptides targeting integrin receptors on tumor cells and carboxymethyl mannose targeting CD206 receptors on macrophages, with a core of chitosan adsorbing m6A reading protein YTHDF1 siRNA and chromium nanoparticles (Cr NPs). The approach is specifically designed to target TAM and cancer cells, utilizing the photothermal effect of Cr NPs to disrupt the TME and deliver siYTHDF1 to TAM. In experiments with tumor-bearing mice, M.RGD@Cr-CTS-siYTHDF1 NPs, when exposed to laser irradiation, effectively killed tumor cells, disrupted the TME, delivered siYTHDF1 to TAMs, silenced the YTHDF1 gene, and shifted the STAT3-STAT1 equilibrium by reducing STAT3 and enhancing STAT1 expression. This reprogramming of TAMs towards an anti-tumor phenotype led to a pro-immunogenic TME state. The strategy also suppressed immunosuppressive IL-10 production, increased expression of immunostimulatory factors (IL-12 and IFN-γ), boosted CD8 + T cell infiltration and M1-type TAMs, and reduced Tregs and M2-type TAMs within the TME. In conclusion, the dual-targeting M.RGD@Cr-CTS-siYTHDF1 NPs, integrating dual-targeting capabilities with photothermal therapy (PTT) and RNA interference, offer a promising approach for molecular targeted cancer immunotherapy with potential for clinical application. Graphical Abstract
研究领域:
癌症生物学
·
纳米技术
·
免疫疗法
·
分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2021
·
IF 9.381
Yunfeng Wan,Wenjie Yu,Jiami Li,Na Peng,Xiao Ding,Yanlong Wang,Tao Zou,Yang Cheng,Yi Liu
Current challenge of using cytokines is its poor distribution and systemic side effects. To avoid this issue, we prepared the tumor-targeted and microenvironment-responsive nanocarriers (TRN), which were consisted of α-tocopheryl succinate (α-TOS) loaded mesoporous silica nanoparticles as cores, and surface-modified by thioketal-linkage, electrostatically coated with carboxymethyl chitin , and further anchored glucose-regulated protein 78-binding peptide as shells for encapsulating IL-12. TRN showed a size of 260 nm after encapsulated IL-12 and α-TOS with loading content of 0.0206% and 7.21%, respectively, and exhibited good biocompatibility to 4 T1 cells and macrophages. Moreover, IL-12/α-TOS loaded TRN displayed obvious anti-tumor efficacy on BALB/c nude mice bearing 4 T1 tumors, which was derived from promoted targeting to tumor tissue, endocytosed by macrophages and locally release IL-12 to subsequently repolarize tumor-associated macrophages into tumoricidal M1 phenotype with reduced side effects. The nanosystem exhibited as a promising strategy with functional conversion of macrophages in tumor microenvironment for anti-tumor therapy.
研究领域:
纳米技术
·
肿瘤学
·
免疫疗法
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2022
·Vol. 24
·期 6
·1-8
·
IF 2.751
Na Ren,Shanshan Shi,Na Zhao,Lingyan Zhang
Dual specificity phosphatase 22 (DUSP22) regulates fibrosis and inflammation, which may be implicated in the development of diabetic nephropathy (DN). Hence, the current study aimed to assess the effect of DUSP22 on cell proliferation, apoptosis, fibrosis and inflammation in mouse mesangial cell line (SV40‑MES13) under both high glucose (HG) and low glucose (LG) conditions. SV40‑MES13 cells were treated with HG and LG, then HG‑group cells were transfected with DUSP22 overexpression and control plasmids, meanwhile LG‑group cells were transfected with DUSP22 and control siRNAs. Then, cell proliferation using Cell Counting Kit‑8, cell apoptosis by TUNEL assay, protein expression using western blotting, inflammatory cytokines using ELISA and RNA using reverse transcription‑quantitative PCR were determined. DUSP22 mRNA and protein were decreased in SV40‑MES13 cells under the HG condition compared with those under the LG condition. Under the HG condition, DUSP22 overexpression suppressed SV40‑MES13 cell proliferation at 48 and 72 h as well as Bcl2, but it facilitated TUNEL‑reflected apoptotic rate and cleaved‑caspase‑3; besides, DUSP22 overexpression restrained proteins of fibronectin 1, collagen I, transforming growth factor beta 1, and their corresponding mRNAs. As to the inflammation, DUSP22 overexpression downregulated TNF‑α, IL‑1β, IL‑6 and IL‑12 under the HG condition. By contrast, DUSP22 siRNA promoted SV40‑MES13 cell proliferation, fibrosis and inflammation, but attenuated apoptosis in SV40‑MES13 cells under the LG condition. Additionally, DUSP22 overexpression inactivated phosphorylated (p)‑ERK, p‑JNK, and p‑P38 in HG‑treated SV40‑MES13 cells; differently, DUSP22 small interfering RNA facilitated them under the LG condition. In conclusion, DUSP22 suppresses HG‑induced mesangial cell hyperproliferation, fibrosis, inflammation and the MAPK pathway, implying its potency in DN treatment.
研究领域:
分子生物学
·
细胞生物学
·
糖尿病研究
·
肾病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2021
·
IF 8.947
Xinran Song,Yuxin Jiang,Weixing Zhang,Gomaa Elfawal,Kaili Wang,Di Jiang,Huoyan Hong,Jinglei Wu,Chuanglong He,Xiumei Mo,Hongsheng Wang
Transcutaneous immunization (TCI) has the advantages of safety, high efficiency, non-invasiveness and convenient use. The key for a TCI system is transdermal targeted delivery of antigen to dendritic cells (DCs), the most powerful antigen presenting cells . DCs also play an important role in tumor immunotherapy, which provides a huge imagination for the application of TCI to tumor treatment. In this study, a transcutaneous tumor vaccine (TTV) delivery system was developed using the electrospun silk fibroin (SF) and polyvinyl alcohol (PVA) composite nanofibrous patch loaded with mannosylated polyethyleneimine (PEI man )-modified ethosome (Eth) (termed Eth-PEI man ). Eth-PEI man showed a good performance in targeting DCs, and the carriers loaded with antigen (encapsulated in Eths) and adjuvant (absorbed in PEI man ) were observed effectively induce DCs maturation in vitro. With the tyrosinase-related protein-2 (TRP2) peptide as antigen and oligodeoxynucleotides containing unmethylated CpG motifs as adjuvant, the TTV-loaded patches (TTVP) significantly inhibited the growth of melanoma in a syngeneic mouse model for melanoma by subcutaneous injection of B16F10 cell lines. Moreover, the combined application of the TTVP and anti-programmed death-1 monoclonal antibody (aPD-1) produced a synergistic antitumor effect, which could be related to the infiltration of more CD4 + and CD8 + T cells in the tumor tissues. The application of TTVP also increased the expression of IL-12, which may be part of the mechanism of synergistic antitumor effect between the TTVP and aPD-1. These results suggest that the combination of the TTVP and immune checkpoint blockers could be an effective strategy for tumor treatment. Statement of significance Transcutaneous immunization has the advantages of safety, high efficiency, non-invasiveness and convenient use. In this study, a novel transcutaneous tumor vaccine patch (TTVP) was developed using tumor antigens-loaded ethosomes that can target dendritic cells percutaneously. Our data demonstrated that the TTVP can significantly inhibit tumor growth. Furthermore, the combination of TTVP and aPD-1 produced a synergistic anti-melanoma effect. Considering its convenience and non-invasiveness, this TTVP system could find good application prospects in immunotherapy. The combination of TTVP and aPD-1 could be a useful strategy for the prevention and treatment of tumors.
研究领域:
免疫学
·
肿瘤学
·
药学
·
生物技术
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2022
·
IF 8.786
Tian Xiaoying,Fan Rongbo,He Hong,Cui Qingyu,Liang Xi,Liu Qiqi,Liu Tongjie,Lin Kai,Zhang Zhe,Yi Huaxi,Gong Piming,Zhang Lanwei
Food allergy is a serious public health problem because of its high incidence and risk. Probiotics can induce immune regulation in patients with allergic diseases, but its mechanism is not fully clear. In this paper, β-lactoglobulin (β-LG)-sensitized mice were used as models to explore the mechanism of Bifidobacterium animalis KV9 (KV9) and Lactobacillus vaginalis FN3 (FN3) on reducing allergic reactions and regulating immune cell function. The results showed that oral administration of KV9 and FN3 significantly reduced the scores of allergic symptoms, hypothermia symptoms, and serum levels of β-LG-specific immunoglobulins E (β-LG-sIgE), histamine, and mast cell protease in allergic mice. Flow cytometry analysis of intestinal dendritic cells (DCs) showed that the proportion of CD11c+major histocompatibility complex (MHC)-II+DCs, CD11c+CD80+DCs, and CD11c+ CD86+DCs increased after KV9 and FN3 intervention, indicating that the strains induced immature DCs and decreased the antigen-presenting capacity of DCs. Meanwhile, the toll-like receptor 4 (TLR4)-NF-κB signaling pathway was activated in DCs. The secretion of interleukin-12 (IL-12) was significantly increased, while interleukin-4 (IL-4) was decreased by DCs after KV9 and FN3 intervention, indicating that DCs have the potential to promote T-cell differentiation into T helper type 1 (Th1) cells. Furthermore, the proportion of CD3+CD8−IFN-γ+ T cells in the spleen increased, while CD3+CD8−IL-4+T cells decreased after oral administration of KV9 and FN3, correcting the T helper type 2 (Th2)-skewed immune responses. These results indicate that KV9 and FN3 reduce β-LG-induced allergic symptoms in mice, and suggest that the two potential probiotics might be used as an alternative therapeutic agent for mitigating food allergy.
研究领域:
免疫学
·
微生物学
·
过敏学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Zhiting Cao,Jianye Ren,Yuguan Huang,Tong Li,Zhen Wang,Zhangyi Miao,Jia Jia,Yang Ding
Epidermal immunotherapy represents an emerging treatment method for allergic diseases. Nevertheless, an unformidable obstacle for epidermal drug delivery is the dense stratum corneum of the skin. Here, iontophoresis technology is utilized for epidermal delivery of allergen protein. Briefly, an iontophoresis patch consists of conductive nanofiber polypyrrole (PPy) and polyvinyl alcohol (PVA) by electrospinning technology, onto which cationic lipid dioctadecyl–dimethylammonium bromide vesicles containing ovalbumin (DDA@OVA) are loaded via electrospraying technology, forming a stable in situ composite structure. Compared with DDA@OVA/PVA, DDA@OVA/PPy-PVA demonstrated a significant increase in both allergen release and penetration into the epidermis. Ultimately, a high-level activation of antigen-presenting cells is facilitated. Importantly, DDA@OVA/PPy-PVA induces a significant increase in the levels of helper T cell 1 (Th1)-related cytokines such as IFN-γ and IL-12, inhibits the differentiation of T cells into Th2 cells, and further affects the secretion of OVA-specific IgE and promotes the production of protective antibody IgG. The lung tissue analysis illustrates that DDA@OVA/PPy-PVA treatment achieves regular alveolar structures in the lumen and significantly relieved asthma symptoms. The findings indicate that iontophoresis patches provide multiple benefits, including drug-responsive release, efficient penetration, and advanced therapeutic efficacy. These attributes make iontophoresis patches a promising treatment option for allergic diseases.
研究领域:
生物医学工程
·
药学
·
免疫学
·
过敏研究
·
药物递送系统
·
纳米技术
·
材料科学
·
呼吸系统疾病
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）