Multifunctional Lipid Bilayer Nanocarriers for Cancer Immunotherapy in Heterogeneous Tumor Microenvironments, Combining Immunogenic Cell Death Stimuli with Immune Modulatory Drugs.
Multifunctional Lipid Bilayer Nanocarriers for Cancer Immunotherapy in Heterogeneous Tumor Microenvironments, Combining Immunogenic Cell Death Stimuli with Immune Modulatory Drugs.
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DOI：
10.1021/acsnano.2c01252
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发表时间：
2022-04-26
期刊：
影响因子：
17.1
通讯作者：
Liu, Xiangsheng
中科院分区：
文献类型：
--
作者：
Nel, Andre E.;Mei, Kuo-Ching;Liao, Yu-Pei;Liu, Xiangsheng
关键词：
除了癌细胞的贡献外，实体肿瘤微环境（TME）在决定肿瘤扩张、抗肿瘤免疫和对免疫治疗的反应方面也发挥着关键作用。了解癌细胞与TME组分之间复杂相互作用的细节，为探索干预免疫环境以改善免疫治疗结果的联合疗法提供了前所未有的机会。一种方法是引入多功能纳米载体，其能够递送提供免疫原性刺激以改善肿瘤抗原呈递的药物组合，同时递送提供免疫危险信号或干扰免疫逃逸、免疫抑制和T细胞排斥途径的共配制药物或合成分子。这一前瞻性的观点将讨论使用脂质双层封装的脂质体和介孔二氧化硅纳米粒子的异质性免疫景观在胰腺导管腺癌（PDAC）和三阴性乳腺癌（TNBC）的联合免疫治疗。我们描述了远程药物装载和脂质双层包封的组合如何用于合成协同药物组合，其诱导免疫原性细胞死亡，干扰PD-1/PD-L1轴，抑制吲哚胺-吡咯2，3-双加氧酶（IDO-1）免疫代谢途径，恢复活化T细胞对癌细胞的空间访问，或减少免疫抑制性基质组分的影响。我们展示了如何将现有知识和未来发现整合用于纳米癌症免疫治疗的合理方法。
In addition to the contribution of cancer cells, the solid tumor microenvironment (TME) has a critical role in determining tumor expansion, antitumor immunity and the response to immunotherapy. Understanding the details of the complex interplay between cancer cells and components of the TME provides an unprecedented opportunity to explore combination therapy for intervening into the immune landscape to improve immunotherapy outcome. One approach is the introduction of multifunctional nanocarriers, capable of delivering drug combinations that provide immunogenic stimuli for improvement of tumor antigen presentation, contemporaneous with the delivery of co-formulated drug or synthetic molecules that provide immune danger signals or interfere in immune escape, immune suppressive and T-cell exclusion pathways. This forward-looking perspective will discuss the use of lipid bilayer encapsulated liposomes and mesoporous silica nanoparticles for combination immunotherapy of the heterogeneous immune landscapes in pancreatic ductal adenocarcinoma (PDAC) and triple negative breast cancer (TNBC). We describe how the combination of remote drug loading and lipid bilayer encapsulation is used for the synthesis of synergistic drug combinations that induce immunogenic cell death, interfere in the PD-1/PD-L1 axis, inhibit the indoleamine-pyrrole 2,3-dioxygenase (IDO-1) immune metabolic pathway, restore spatial access to activated T-cells to the cancer cells, or reduce the impact of immunosuppressive stromal components. We show how an integration of current knowledge and future discovery can be used for a rational approach to nano-enabled cancer immunotherapy.
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