Nanoscale
·
2024
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IF 5.8
yaoyao guo,Manzhen Li,xinxin liu,xi wang,ziqi zhang,dongchun liu,Xiangtao Wang
Nearly all the anti-tumor drugs can benefit greatly from tumor-targeted delivery for improved therapeutic efficacy and reduced toxic side effects. However, the vast majority of tumor-targeting ligands can only target to specific tumor cells highly expressed the corresponding receptors and thus applicable to limited tumor types. Heptadecyanines with medium cyclohexene and medium -Cl atoms, such as IR780 and IR808, have shown an unusual ability to indiscriminately accumulate into virtually all tumor types. In this study, IR808 was conjugated with DSPE-mPEG2000-NH2 and the resultant DSPE-PEG2000-IR808 (DP-IR808) in combination with TPGS, successfully encapsulated paclitaxel (PTX) and immunomodulator R848 into nanoparticles with a small particle size of 150.20 nm, a negative charge of -16.50 mV, rod-like morphology and a PTX loading content of 31.6 %. The obtained DP-IR808@PTX-R848 NPs rapidly accumulated into 4T1 tumors with a tumor/liver fluorescence ratio of 1.71 and a significant photothermal effect and could be directly used for NIR imaging. DP-IR808@PTX-R848 NPs achieved a high tumor inhibition rate of 94%, a mean survival time of > 90 d and a tumor-free survival percentage of 57%. As far as we know, this was the first time that nanoparticles were modified with heptamethylcyanine molecules. Nanoparticles based on DSPE-PEG-IR808, which integrates tumor targeted drug delivery, in vivo infrared imaging and photothermal therapy, is expected to become a versatile drug delivery platform for tumor therapy.
研究领域:
药剂学
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肿瘤学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2023
·
IF 5.8
Zeting Yuan,Hai He,Jiafeng Zou,Hongtao Wang,You Chen,Yang Chen,Minbo Lan,Yuzheng Zhao,Feng Gao
Breast cancer, which requires comprehensive multifunctional treatment strategies, is a major threat to the health of women. To develop multifunctional treatment strategies, we combined photothermal therapy (PTT) with immunotherapy in multifunctional nanoparticles for enhancing the anti-tumor efficacy. Fe 3 O 4 nanoparticles coated with the polydopamine shell modified with polyethylene glycol and cyclic arginine-glycyl-aspartic peptide/anisamide (tNP) for loading the immune adjuvant resiquimod (R848) ( [email protected] ) were developed in this research. [email protected] had a round-like morphology with a mean diameter of 174.7±3.8 nm, the zeta potential of -20.9±0.9 mV, the drug loading rate of 9.2±1.1%, the encapsulation efficiency of 81.7±3.2%, high photothermal conversion efficiency and excellent magnetic properties in vitro . Furthermore, this research also explored the anticancer efficacy of nanoparticles against the breast cancer under the near-infrared (NIR) light (808 nm) in vitro and in vivo . [email protected] NIR therapy effectively inhibited the proliferation of breast cancer cells. Moreover, [email protected] mediated PTT significantly enhanced the maturation of dendritic cells in vitro . Additionally, [email protected] enhances the anti-tumor effect and evoked an immune response under NIR in vivo . Furthermore, the biosafety of [email protected] was fully investigated in this study. Collectively, these results clearly demonstrate that [email protected] , with magnetic resonance imaging characteristics, is a potential therapeutic for breast cancer that combines PTT with the immunotherapy.
研究领域:
癌症研究
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纳米技术
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治疗学
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免疫学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2021
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IF 6.4
Xinghan Liu,Yujun Xu,Lijie Yin,Yayi Hou,Shuli Zhao
Purpose Since immune cells in the tumor microenvironment (TME) can affect the development and progression of tumors, strategies modulating immune cells are considered to have an important therapeutic effect. As a TLR7/8 agonist, R848 effectively activates the innate immune cells to exert an anti-tumor effect. Mn 2+ has been reported to strongly promote the maturation of antigen-presenting cells (APCs), thereby enhancing the cytotoxicity of CD8 + T cells. Thus, we tried to investigate whether chitosan-poly(acrylic acid) nanoparticles (CS-PAA NPs) loaded with R848 and MnCl 2 (R-M@CS-PAA NPs) could exert an anti-tumor effect by regulating the function of immune cells. Methods R-M@CS-PAA NPs were prepared, and their basic characteristics, anti-tumor effect, and potential mechanisms were explored both in vitro and in vivo. Results R-M@CS-PAA NPs easily released MnCl 2 and R848 at low pH. In B16F10 mouse melanoma model, R-M@CS-PAA NPs exerted the most significant anti-melanoma effect compared with the control group and CS-PAA NPs loaded with R848 or MnCl 2 alone. FITC-labeled R-M@CS-PAA NPs were displayed to be accumulated at the tumor site. R-M@CS-PAA NPs significantly increased the infiltration of M1 macrophages and CD8 + T cells but reduced the number of suppressive immune cells in the TME. Moreover, in vitro experiments showed that R-M@CS-PAA NPs polarized macrophages into the M1 phenotype to inhibit the proliferation of B16F10 cells. R-M@CS-PAA NPs also enhanced the killing function of CD8 + T cells to B16F10 cells. Of note, R-M@CS-PAA NPs not only promoted the maturation of APCs such as dendritic cells and macrophages by STING and NF-кB pathways, but also enhanced the ability of dendritic cells to present ovalbumin to OT-I CD8 + T cells to enhance the cytotoxicity of OT-I CD8 + T cells to ovalbumin-expressing B16F10 cells. Conclusion These data indicate that the administration of R-M@CS-PAA NPs is an effective therapeutic strategy against melanoma.
研究领域:
药理学
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免疫学
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纳米技术
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2022
·Vol. 10
·期 5
·1257-1266
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IF 7.59
Yandi Liu,Yu-Yang Han,Sha Lu,Yingjiao Wu,Juan Li,Xiaoyi Sun,Jun Yan
Photothermal therapy (PTT) is a powerful strategy for cancer treatment with minimal invasiveness but still limited by lack of long-term efficacy against tumor recurrence and toxicity concerns about the slow biodegradability of the PTT agents. Herein, an injectable hydrogel platform (R848/POM@GG) of gellan gum co-loaded with Dawson-type {P2Mo18} polyoxometalate (POM) and Toll-like receptors agonist resiquimod (R848) is developed for combinational photothermal-immunotherapy of cancer. The POM-based gellan gum hydrogel (POM@GG) exhibits high photothermal conversion efficiency (63.1%) at a safe power density of 0.3 W cm−2 and good photostability during five cycles. By further incorporation of R848, the obtained R848/POM@GG exerts synergetic photothermal-immunotherapy on solid tumors, giving a high tumor inhibition rate of 99.3% and negligible lung metastases in the breast cancer mice models. A strong antitumor immune system with significantly elevated TNF-α, IL-2, and IL-6 levels is activated by R848. Additionally, the POM clusters gradually degrade to nontoxic molybdate in the physiological environment. Overall, the injectable hydrogel platform of R848/POM@GG has great translational potential for localized antitumor treatments.
研究领域:
癌症治疗
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材料科学
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免疫学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
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IF 9.4
Pinxin Lv,Zhanfeng Wang,Xinghui Si,Jing Su,Zhifei Yu,Hongquan Yu,Guofeng Ji,Wantong Song
Glioblastoma (GBM), a prevalent and aggressive brain tumor, poses significant treatment challenges due to its rapid progression and the difficulty in achieving complete surgical resection. The current treatment regime, primarily surgery followed by radiotherapy and chemotherapy, offers limited success, with a five-year survival rate of less than 10%. For addressing the challenges faced in the treatment of GBM, an approach using a biopolymer implant constructed with dynamic reversible covalent bonds, was designed to achieve controlled and constant-rate release of chemotherapy drug (Temozolomide, TMZ), immune adjuvant (Resiquimod, R848) and checkpoint inhibitor (5-carboxy-8-hydroxyquinoline, IOX1). The safety evaluation demonstrated the biocompatibility of the implants, with no significant inflammatory response or adverse effects on various systemic organs. In vivo antitumor study showed that the local delivery of drug combination via this implant significantly inhibited tumor recurrence of orthotopic GBM. Immune analysis revealed that the combination of the three drugs effectively activated systemic antitumor immune responses and induced memory effects. The synergistic mechanism of the drug combination was further validated by RNA whole sequencing. The innovative approach of combining chemotherapy and immunotherapy in biopolymer immune implants for GBM treatment showed promising and opens new avenues for treating GBM, particularly in addressing postoperative recurrence. Statement of Significance Our research introduces a pioneering approach in treating orthotopic brain glioblastoma (GBM), characterized by inevitable tumor recurrence, poor immune infiltration and the restrictive nature of the blood-brain barrier. To break the impasse of ineffective treatment for GBM, the innovative use of dynamically reversible covalent bonds in polymer matrix ensures the controlled, stable and sustained release of drug combinations of the chemotherapeutic agent temozolomide, immune adjuvants and checkpoint inhibitors, which maintains the optimal concentration in the tumor, overcoming problems associated with conventional chemotherapy such as systemic toxicity and low tumor targeting. Empirical evidence from in vivo experiments on the rat GBM model demonstrates significant outcomes: 90% tumor size reduction and prolonged survival with over 70% tumor cure rate.
研究领域:
肿瘤学
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生物材料科学
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免疫治疗
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神经科学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
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2024
·
IF 5.3
Houyang Hu,Xuechun Wang,Yilei Zhao,Jie Yan,Songyan Li,Chengzhilin Li,Xiaonan Zhao,Kanaparedu P. C. Sekhar,Ming Xia,Jianwei Jiao,Miaoqing Zhao,Guiqiang Zhang
Effective therapeutic approaches against head and neck squamous cell carcinoma (HNSCC), which is a prevalent malignant tumor, are currently lacking. Although immunotherapy has emerged as a promising strategy for treating HNSCC, its efficacy is severely limited by the immunosuppressive tumor microenvironment. Self-delivery nanoparticles, comprising Toll-like receptor (TLR) agonists and photosensitizers, were successfully developed to address this challenge in combinatorial immunotherapy for HNSCC treatment. After intravenous administration, these nanoparticles efficiently accumulated in tumors, enhancing the bioavailability of the agonist and triggering the TLR signaling pathway to remodel the immunosuppressive tumor microenvironment. Simultaneously, the photosensitizers induced immunogenic cell death and activated the stimulator of the interferon gene (STING) pathway in tumor cells via photodynamic therapy. The development of tumors was significantly inhibited by enhancing the antitumor immunity induced by the nanoparticles. This study provided a new paradigm for HNSCC immunotherapy, involving the synergistic regulation of the immune microenvironment with photodynamic therapy.
研究领域:
肿瘤学
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免疫学
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纳米医学
✓ 已验证
产品关联
DOI
高影响因子
Biomaterials Science
·
2026
·
IF 6.1
Qi Zhang,Luyao Wang,Zhaofan Yang,Hao Meng,Shixian Lv,Linlin Liu
Chemo-immunotherapy aims to integrate chemotherapy-induced antigen release with innate immune activation to achieve enhanced antitumor efficacy. However, the pharmacokinetic mismatch and systemic toxicity of free small molecules often compromise the synergistic effects. Herein, we propose a reactive oxygen species (ROS)-responsive nanoplatform based on mPEG–PCL for the co-delivery of a paclitaxel (PTX) prodrug and the TLR7/8 agonist R848. The nanoparticles remain stable under physiological conditions while releasing drug in oxidative tumor microenvironments, thereby achieving synchronous intratumoral delivery and activation. In vitro, the system exhibited efficient intracellular uptake and potent cytotoxicity against tumor cells while maintaining low toxicity toward normal cells due to prodrug design. Moreover, the platform effectively induced immunogenic cell death and promoted dendritic cell maturation, highlighting its capacity for chemo-immunotherapeutic synergy. This co-delivery strategy provides a versatile approach to realize controllable and safe chemo-immunotherapy through stimuli-responsive nanomedicine design.
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DOI
PubMed
高影响因子
Biomaterials Science
·
2025
·
IF 5.7
Jia-Qi Luo,Yong-Cong Huang,Jing-Yang Zhang,Qi-Song Tong,Areesha Batool,Jinzhi Du,Yuyou Duan
Antigen-presenting cells (APCs), such as macrophages and dendritic cells (DCs) are key players in modulating the immune responses of cytotoxic T lymphocytes (CTLs). Resiquimod (R848), a toll-like receptor (TLR) agonist, has demonstrated the capacity to enhance APC function and reprogram the phenotype of macrophages; however, the unfavorable in vivo performance constrains its therapeutic potential. Here, we developed R848-loaded mesoporous silica nanoparticles (denoted as R848@MSN-bi-PEG) with pH-responsive surface PEG detachment to effectively modulate APCs. The acidic tumor pH triggered PEG detachment when R848@MSN-bi-PEG accumulated at the tumor site, thereby promoting APC uptake and R848 release, which facilitated DCs maturation and macrophage repolarization to a pro-inflammatory phenotype. The in vivo antitumor study indicated that R848@MSN-bi-PEG led to potent anti-tumor immunity by modulating the immunosuppressive tumor microenvironment. This approach offers a novel strategy to improve the effectiveness of cancer immunotherapy.
研究领域:
生物医学工程
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免疫学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Mengyao Ma,Ximu Li,Mingyuan Zhong,Xuejing Li,Jiang Yu,Zhaomeng Wang,Qingzhi Lv,Xin Li,Zhonggui He,Hongzhuo Liu,Yongjun Wang
Cancer vaccines, a critical technology in cancer immunotherapy, have shown great therapeutic potential. However, traditional vaccines based on tumor cell lysates (TCLs) have shown disappointing results in early clinical trials due to low immunogenicity, in vivo instability, and the inability to codeliver with adjuvants. To address these issues, we developed a nanoparticle vaccine, R848-GA@TCLs, by modifying the toll-like receptor 7/8 (TLR7/8) agonist R848 with gallic acid. This nanovaccine leverages the “capturing” ability of the galloyl moiety to coload TCLs and R848, forming stable nanoparticles. R848-GA@TCLs efficiently target lymph nodes, increasing TCL accumulation 10-fold, and enable the synchronized release of antigens and adjuvants within dendritic cells (DCs). Our results show that R848-GA@TCLs increase with respect to the cross-presentation of tumor antigens, promote the production of pro-inflammatory cytokines, and activate DCs, leading to a significant increase in effector T cells, natural killer (NK) cells, and M1 macrophages. This strong immune response resulted in potent antitumor effects, with R848-GA@TCLs demonstrating efficacy in multiple tumor models by significantly inhibiting tumor growth and metastasis. In conclusion, R848-GA@TCLs represent a personalized cancer vaccine capable of codelivering TCLs and adjuvants, eliciting robust antitumor immune responses, and hold great potential for clinical applications.
研究领域:
肿瘤学
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免疫学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Shanshan Jin,Yongkang Chen,Fahui Li,Ping Yan,Guanhong Guo,Guangzhao Xu,Weiguo Song,Wenda Zhong
Currently, immunotherapy based on photothermal and the application of photodynamic therapy in anti-tumor treatment is showing great potential. Its uniqueness lies in the critical role of small molecule immunomodulators in promoting effective immune responses against tumors, and the use of laser-activated biophysical mechanisms to precisely trigger the swift demise of cancer cells, avoiding damage to surrounding normal tissues. However, the use of photodynamic therapy (PDT) alone is hampered by the tumors’ hypoxic environment, resulting in poor antitumor effects, while photothermal therapy (PTT) alone cannot arouse enough antigen presentation. It is of great significance to design photosensitizers (PSs) that possess both PDT and PTT effects. Herein, a series of PSs with both PDT and PTT efficacy are reported, ultimately selecting Cy7-Naph as the star molecule due to its best overall phototherapeutic effect. Upon reactive oxygen species (ROS) production and thermogenesis in tumor cells, Cy7-Naph induced significant apoptosis and eventually boosted the release of damage-associated molecular patterns (DAMPs) under near-infrared (NIR) light irradiation. By combining Cy7-Naph with the Toll-like receptor agonist Resiquimod (R848), a synergistic treatment for bilateral tumor-bearing mice is achieved. This combination promotes dendritic cell (DC) maturation and increases the infiltration of cytotoxic T lymphocytes (CTLs), leading to significant inhibition of both primary and distant tumors.
研究领域:
生物医学工程
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肿瘤免疫学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Yichi Chen,Wenxin Xu,Huimin Tian,Junbin Gao,Yicheng Ye,Hanfeng Qin,Hong Wang,Yanzhen Song,Chuxiao Shao,Fei Peng,Yingfeng Tu
Light-propelled nanomotors, which can convert external light into mechanical motion, have shown considerable potential in the construction of a new generation of drug delivery systems. However, the therapeutic efficacy of light-driven nanomotors is always unsatisfactory due to the limited penetration depth of near-infrared-I (NIR-I) light and the inherent biocompatibility of the motor itself. Herein, an asymmetric nanomotor (Pd@ZIF-8/R848@M JNMs) with efficient motion capability is successfully constructed for enhanced photoimmunotherapy toward hepatocellular carcinoma. Under near-infrared-II (NIR-II) irradiation, Pd@ZIF-8/R848@M JNMs convert light energy into heat energy, exhibiting self-thermophoretic locomotion to penetrate deeper into tumor tissues to achieve photothermal therapy. At the same time, functionalized with an immune-activated agent Resiquimod (R848), our nanomotors could convert a “cold tumor” into a “hot tumor”, transforming the immunosuppressive microenvironment into an immune-activated state, thus achieving immunotherapy. Dual photoimmunotherapy of the as-developed NIR-II light-driven Pd@ZIF-8/R848@M JNMs demonstrates considerable tumor inhibition effects, offering a promising therapeutic approach in the field of anticancer therapy.
研究领域:
纳米技术
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癌症治疗
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生物医学工程
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光化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
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IF 8.3
Cai Zhang,Zheng Deng,Xianglong Sun,Kangzhi Yuan,Jiadong Wang,Xirui Wu,Yifan Zhang,Kai Yang,Junjun Zhang,Guangbao Yang
The morphological features of materials significantly influence their interactions with cells, consequently affecting the cellular uptake of these materials. In this study, we examine the cellular uptake behavior of spherical metal–organic frameworks (MOFs) and petaloid MOFs, both possessing similar sizes and compositions. In comparison to spherical MOFs, dendritic cells (DCs) and macrophages exhibit superior phagocytic uptake of petaloid MOFs. Next, the results demonstrate that R848@petaloid MOFs more effectively promote the repolarization of tumor-associated macrophages (TAMs) from the M2 to M1 phenotype and the maturation of DCs. More importantly, the R848-loaded petaloid MOFs are found to significantly enhance the therapeutic effects of radiotherapy (RT) by eliciting antitumor responses. Furthermore, R848@petaloid MOFs combined with RT and αPD-L1 elicit a potent abscopal effect, effectively suppressing tumor metastasis. Therefore, this work proposes a new strategy to enhance the uptake of immunomodulators by immune cells through modulating the morphology of drug delivery carriers.
研究领域:
生物材料学
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免疫学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）