Immunotherapy has unprecedentedly opened up a series of neoteric tactics for cancer treatment. As a burgeoning approach, chemo-immunotherapy has innovatively expanded the accomplishments of conventional chemotherapeutic agents for cancer governing. An efficacious chemo-immunotherapy leveraging minimalist electrostatic complex nanoparticle (NP) integrated tumor immunogenic cell death (ICD) and immunoagonist was developed as a watertight “” vaccine for cancer therapy through convenient intratumoral administration with minimized systemic toxicity. Chemical-modified pH-sensitive -aconityl-doxorubicin (CAD) and immunoadjuvant unmethylated cytosine-phosphate-guanine (CpG) were co-packaged by polycationic polyethylenimine (PEI) though electrostatic-interaction to construct PEI/CpG/CAD NP. By intratumoral injection, this positively charged NP could be detained at tumor site and endocytosed by tumor cells effortlessly. Then, doxorubicin was released through -aconityl cleavage induced by endosomal-acidity and further triggered tumor ICD, the moribund tumor cells could release damage-associated molecular patterns (DAMPs) to recruit dendritic cells (DCs). Meanwhile, the entire tumor debris derived into diversified antigens and cooperated with immunostimulatory CpG to excite DC maturation and activated comprehensive antitumor immunity. Prominent tumor suppression was achieved in aggressive mouse melanoma tumor model, which verified the feasibility and effectiveness of this minimalist CAD/CpG-codelivered NP. This study has provided a convenient and promising paradigm for potent cancer chemo-immunotherapy.

中文翻译：

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利用极简静电复合纳米颗粒作为集成肿瘤 ICD 和免疫激动剂的“原位”疫苗进行高效化学免疫治疗

免疫疗法前所未有地开辟了一系列新的癌症治疗策略。作为一种新兴的方法，化学免疫疗法创新性地扩展了传统化疗药物在癌症治疗方面的成就。一种有效的化学免疫疗法，利用最小化的静电复合纳米粒子（NP）集成肿瘤免疫原性细胞死亡（ICD）和免疫激动剂，通过方便的肿瘤内给药和最小化的全身毒性，开发出一种用于癌症治疗的防水“疫苗”。将化学修饰的pH敏感的乌头酰阿霉素（CAD）和免疫佐剂非甲基化磷酸胞嘧啶鸟嘌呤（CpG）通过聚阳离子聚乙烯亚胺（PEI）通过静电相互作用共包装，构建PEI/CpG/CAD NP。通过瘤内注射，这种带正电荷的纳米粒子可以被滞留在肿瘤部位并毫不费力地被肿瘤细胞内吞。然后，内体酸性诱导的α-乌头基裂解释放阿霉素，并进一步触发肿瘤ICD，垂死的肿瘤细胞可以释放损伤相关分子模式（DAMPs）来招募树突状细胞（DCs）。同时，整个肿瘤碎片衍生出多种抗原，与免疫刺激性CpG配合，刺激DC成熟，激活综合抗肿瘤免疫。在侵袭性小鼠黑色素瘤肿瘤模型中实现了显着的肿瘤抑制，验证了这种简约的 CAD/CpG 共传递 NP 的可行性和有效性。这项研究为有效的癌症化学免疫疗法提供了一种方便且有前景的范例。