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CpG-ODNs
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES · 2021 · IF 4.384

Reversing tumor immunosuppressive microenvironment via targeting codelivery of CpG ODNs/PD-L1 peptide antagonists to enhance the immune checkpoint blockade-based anti-tumor effect

Min Zhang,Zhou Fang,Haitao Zhang,Mingxiao Cui,Mingfu Wang,Kehai Liu

In order to reverse tumor immunosuppressive microenvironment and improve antitumor immune effect based on immune checkpoint blocking, a mannose-modified liposome-based CpG ODNs and PD-L1 antagonistic peptides (P) co-delivery system (HA/M-Lipo CpG-P) was constructed, in which hyaluronic acid (HA) coating was supposed to improve the systemic circulation stability and thereby promote its accumulation in tumor tissues. When the HA/M-Lipo CpG-P complexes enter the tumor tissues, HA will be hydrolyzed under the action of hyaluronidase, exposing P peptides. Then, P peptides linked by octapeptides that can be cleaved by matrix metalloproteinases (MMPs) are released into tumor tissues under the action of MMPs, exerting a blocking effect in the PD-1/PD-L1 pathway. The M-Lipo CpG complexes can recognize macrophage surface mannose receptors through its surface modified mannose molecules, and promote the intracellular delivery of CpG ODNs, thereby activating macrophages. The results showed that HA/M-Lipo CpG-P complexes successfully reversed M2-type macrophages in tumor microenvironment (TME) to M1, thereby activating anti-tumor related immune cells and inhibiting tumor growth. Moreover, the HA/M-Lipo CpG-P complexes showed a better tumor inhibitory effect than the HA/M-Lipo CpG or the HA/M-Lipo-P (monotherapy) treatment groups. Overall, HA/M-Lipo CpG-P complexes provide a promising co-delivery strategy for targeting tumors to improve the antitumor effect based on immune checkpoint blockade.

研究领域: 肿瘤学 · 免疫治疗 · 药学 · 纳米技术
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JOURNAL OF NANOPARTICLE RESEARCH · 2024 ·Vol. 26 ·期 2 ·1-13 · IF 2.1

Construction of mannose-grafting Fe-doped carbon dots for CpG delivery and photothermal ablation of tumor

Ye Haiyang,Zhang Li,Qiu Xiaonan,Qiu Jianghong,Xu Wenqing,Xu Xiao,Yu Huijun,Zou Shengqiang,Du Fengyi,Zheng Guojun,Wu Yunchao

Photothermal therapy (PTT) can kill the tumor in situ, but fail to trigger strong antitumor immune response against its recurrence and metastasis. Herein, mannose-grafting Fe-doped carbon dots (M/Fe-CDs) were prepared via hydrothermal carbonization and chemical modification. The prepared M/Fe-CDs had characteristics of excellent optical qualities, good water solubility, and outstanding biocompatibility. Compared with pure CDs, the doping of Fe atom endowed the M/Fe-CDs with a high photothermal conversion efficiency (from 12.1 up to 30.1%). Under 808-nm NIR irradiation, the M/Fe-CDs could lead to local hyperthermia to kill tumor cells. Importantly, the M/Fe-CDs were capable of loading CpG-ODNs via electrostatic absorption and delivering them into the cytoplasm of dendritic cells (DCs). Finally, the CpG-ODNs-loading M/Fe-CDs could significantly increase the CD80/86 expression on the DCs surface. These results demonstrated that the M/Fe-CDs could be used as a versatile nanoplatform to combine the PTT and immune activation for tumor treatment.

CAS / MDL: 7705-08-0
研究领域: 生物医学工程 · 肿瘤免疫学 · 纳米医学
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Nanoscale · 2019 ·Vol. 11 ·期 42 ·19912-19922 · IF 6.97

Tumor microenvironment responsive FePt/MoS2 nanocomposites with chemotherapy and photothermal therapy for enhancing cancer immunotherapy

Dongsheng Zhang,Ping Cui,Zhichao Dai,Baochan Yang,Xiuxiu Yao,Qingyun Liu,Zunfu Hu,Xiuwen Zheng

The metastasis and recurrence of tumors are the main reasons for cancer death. In this work, a promising therapy for tumor treatment that can eliminate primary tumors and prevent tumor relapses is introduced by combining chemotherapy, photothermal therapy (PTT) and immunotherapy. Multifunctional FePt/MoS2-FA nanocomposites (FPMF NCs) were obtained via anchoring FePt nanoparticles and folic acid (FA) on MoS2 nanosheets. As an efficient ferroptosis agent, FePt nanoparticles could catalyze the Fenton reaction to produce the reactive oxygen species (ROS). Through the highly effective photothermal conversion of MoS2 nanosheets, the primary tumor cells could be ablated by photothermal therapy (PTT). Moreover, the metastatic tumors were eliminated effectively with the help of oligodeoxynucleotides containing cytosine–guanine (CpG ODNs) combined with systemic checkpoint blockade therapy using an anti-CTLA4 antibody. Even more intriguingly, a strong immunological memory effect was obtained by this synergistic therapy. Taking all these results into consideration, we anticipate that the photo-chemo-immunotherapy strategies show great promise toward the development of a multifunctional platform for anticancer therapeutic applications.

CAS / MDL: 112-90-3 112-88-9
研究领域: 肿瘤学 · 纳米技术 · 免疫疗法 · 材料科学 · 治疗学
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MOLECULAR PHARMACEUTICS · 2020 · IF 4.321

Hexahistidine–Metal Assemblies: A Facile and Effective Codelivery System of Subunit Vaccines for Potent Humoral and Cellular Immune Responses

Tinghong Zhang,Long Zhang,Xiaoxiao Wu,Hongyan Xu,Pengyan Hao,Wenjuan Huang,Yagang Zhang,Xingjie Zan

Fully effective vaccines must induce both potent humoral and cellular immunities. Nanoparticles coencapsulating antigens and adjuvants have shown promising advantages as subunit vaccines in many aspects. However, the low loading efficiency and complicated synthesis process of these nanomaterials need to be improved. Here, we utilized hexahistidine (His6)–metal assembly (HmA) particles as carriers to codeliver ovalbumin peptides and cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs). We found that antigen/adjuvant-carrying HmA can efficiently enter into antigen-presenting cells and help the antigens escape from lysosomes to induce the maturation of these cells in vitro, characterized by increasing expression levels of costimulatory molecules and cytokines. More importantly, the vaccines with high biocompatibility can elicit strong humoral and cellular immunities by improving secretion of specific antibodies and cytokines, enhancing activation of DCs and T cells in vivo. Our results suggest that HmA provides a new approach for subunit vaccines by codelivery of antigens and adjuvants.

研究领域: 疫苗学 · 免疫学 · 纳米技术 · 生物医学工程
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ACS Biomaterials Science & Engineering · 2021 · IF 4.749

Sodium Alginate Hydrogel-Mediated Cancer Immunotherapy for Postoperative In Situ Recurrence and Metastasis

Yingying Zhang,Tiange Wang,Yinping Zhuang,Tiandi He,Xiaoli Wu,Lin Su,Jun Kang,Jin Chang,Hanjie Wang

With the development of technology, adjuvant immunotherapy has become a promising strategy for prevention of postoperative tumor regression and metastasis by stimulating the host immune response. However, the therapeutic effects are still unsatisfactory due to the lack of synergy between different methods. In this study, an efficient synergistic immunotherapy system based on injectable sodium alginate hydrogels was designed to inhibit in situ recurrence and metastasis at the same time. On the one hand, an injectable sodium alginate (SA) hydrogel microsystem loaded with toll-like receptor (TLR) agonists (CpG ODNs) was synthesized for inhibiting in situ recurrence, and then carcinoembryonic antigen (CEA) probe was also added to detect CEA based on fluorescence resonance energy transfer (FRET) technology to monitor the occurrence and development of tumor recurrence. On the other hand, an anti-programmed cell death 1 ligand 1 antibody (anti-PD-L1)-modified SA nanogel loaded with indocyanine green (ICG@SA-anti-PD-L1 nanogel) was prepared for diagnosing and inhibiting lung metastasis by assisting orthotopic tumor therapy. In vitro and in vivo results demonstrated that this SA micro/nanosystem could monitor and inhibit postoperative recurrence and metastasis. We hope that this micro/nano-synergistic system will become an effective strategy for postoperative adjuvant immunotherapy.

研究领域: 肿瘤学 · 免疫学 · 生物材料 · 纳米技术 · 生物医学工程
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