<br>介孔聚多巴胺靶向CDK4/6抑制剂对乳腺癌的协同免疫治疗,Small

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介孔聚多巴胺靶向CDK4/6抑制剂对乳腺癌的协同免疫治疗
Small ( IF 13.0 ) Pub Date : 2024-02-23 , DOI: 10.1002/smll.202310565
Conglei Zhou ₁ , Shuang Zhao ₁ , Yongbo Zhang ₁ , Jianjun Cheng _{1,

2} , Jiahua Shi _{1,

2} , Guanhua Du _{1,

2,

3}

Affiliation

利用抗 PD-L1 阻断的免疫疗法在临床乳腺癌治疗中取得了巨大成功，但常常受到有限的免疫反应的阻碍。越来越多的证据表明，免疫原性细胞死亡（ICD）最近成为一种有前途的策略，可以有效地扩大肿瘤免疫原性并引发全身抗肿瘤免疫。然而，开发简单但通用、高效但低毒、生物安全且临床可用的转化ICD诱导剂仍然是一个巨大的需求，并且是非常可取的。在此，通过以简单的方式集成光热疗法（PTT）纳米平台介孔聚多巴胺（MPDA）、CDK4/6抑制剂palbociclib（PAL）和CD44特异性靶向A6肽，有目的地开发了多功能ICD诱导剂A6-MPDA@PAL，以增强抗PD-L1疗法的免疫抗肿瘤功效。值得注意的是，光诱导纳米平台表现出多种有利的治疗特性，确保了卓越且生物安全的 PTT/化疗功效。与更强的累积 ICD 诱导相结合，单次给药 A6-MPDA@PAL 可以在抗 PD-L1 阻断的帮助下，通过吸引 T 淋巴细胞的瘤内浸润并同时逆转免疫抑制的肿瘤微环境，从而触发强大的全身抗肿瘤免疫和远隔效应。疗法实现了出色的协同免疫治疗和有效的肿瘤消融。这项研究提出了一种简单而智能的 ICD 诱导剂，为加强乳腺癌的抗 PD-L1 治疗开辟了有吸引力的临床可能性。

"点击查看英文标题和摘要"

Mesoporous polydopamine Targeting CDK4/6 Inhibitor toward Brilliant Synergistic Immunotherapy of Breast Cancer

Immunotherapy utilizing anti-PD-L1 blockade has achieved dramatic success in clinical breast cancer management but is often hampered by the limited immune response. Increasing evidence shows that immunogenic cell death (ICD) recently arises as a promising strategy for enlarging tumor immunogenicity and eliciting systemic anti-tumor immunity effectively. However, developing simple but versatile, highly efficient but low-toxic, biosafe, and clinically available transformed ICD inducers remains a huge demand and is highly desirable. Herein, a multifunctional ICD inducer is purposefully developed A6-MPDA@PAL by integrating photothermal therapy (PTT) nanoplatforms mesoporous polydopamine (MPDA), CDK4/6 inhibitor palbociclib (PAL), and CD44-specific targeting A6 peptide in a simple way for augmenting the immune antitumor efficacy of anti-PD-L1 therapy. Remarkably, the light-inducible nanoplatforms exhibit multiple favorable therapeutic features ensuring a superior and biosafe PTT/chemotherapy efficacy. Together with stronger accumulative ICD induction, single administration of A6-MPDA@PAL can trigger robust systemic antitumor immunity and abscopal effect with the assistance of anti-PD-L1 blockade by fascinating the intratumoral infiltration of T lymphocytes and reversing the immunosuppressive tumor microenvironment simultaneously, therapy achieving brilliant synergistic immunotherapy with effective tumor ablation. This study presents a simple and smart ICD inducer opening up attractive clinical possibilities for reinforcing the anti-PD-L1 therapy against breast cancer.

更新日期：2024-02-23

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