Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan, 430022, China.
J Nanobiotechnology. 2023 Sep 26;21(1):347. doi: 10.1186/s12951-023-02106-8.
Cancer therapeutic vaccine can induce antigen-specific immune response, which has shown great potential in cancer immunotherapy. As the key factor of vaccine, antigen plays a central role in eliciting antitumor immunity. However, the insufficient antigen delivery and low efficiency of antigen presentation by dendritic cells (DCs) have greatly restricted the therapeutic efficiency of vaccine. Here we developed a kind of DC hybrid zinc phosphate nanoparticles to co-deliver antigenic peptide and photosensitive melanin. Owing to the chelating ability of Zn, the nanoparticles can co-encapsulate antigenic peptide and melanin with high efficiency. The nanovaccine showed good physiological stability with the hydration particle size was approximately 30 nm, and zeta potential was around - 10 mV. The nanovaccine showed homologous targeting effect to DCs in vivo and in vitro, efficiently delivering antigen to DCs. Meanwhile, the nanovaccine could effectively reflux to the tumor-draining lymph nodes. When combined with near-infrared irradiation, the nanovaccine induced effective mild heat in vitro and in vivo to promote antigen presentation. After administrating to MC38 tumor-bearing mice, the hybrid nanovaccine effectively promoted the maturation of DCs, the expansion of cytotoxic T lymphocytes and helper T cells, and the secretion of immunostimulatory cytokines, thereby significantly inhibiting tumor growth.
癌症治疗性疫苗可以诱导抗原特异性免疫反应,在癌症免疫治疗中显示出巨大的潜力。作为疫苗的关键因素,抗原在引发抗肿瘤免疫中起着核心作用。然而,树突状细胞(DCs)中抗原的递呈效率不足和抗原提呈效率低下极大地限制了疫苗的治疗效果。在这里,我们开发了一种 DC 混合磷酸锌纳米粒子来共递呈抗原肽和光敏黑色素。由于 Zn 的螯合能力,纳米粒子可以高效地共包封抗原肽和黑色素。纳米疫苗具有良好的生理稳定性,水合粒径约为 30nm,zeta 电位约为-10mV。纳米疫苗在体内和体外均表现出对 DCs 的同源靶向作用,将抗原有效地递送至 DCs。同时,纳米疫苗可以有效地回流到肿瘤引流淋巴结。当与近红外辐射结合时,纳米疫苗在体外和体内诱导有效的温和热以促进抗原呈递。将混合纳米疫苗给予 MC38 荷瘤小鼠后,有效促进了 DCs 的成熟、细胞毒性 T 淋巴细胞和辅助性 T 细胞的扩增以及免疫刺激性细胞因子的分泌,从而显著抑制肿瘤生长。
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