Oxygen-carrying semiconducting polymer nanoprodrugs induce sono-pyroptosis for deep-tissue tumor treatment

Fengshuo Wang, Yongliang Fan, Yue Liu, Xiangxin Lou, Linawati Sutrisno, Shaojun Peng, Jingchao Li
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Abstract

Sonodynamic therapy (SDT) has been explored for cancer therapy, especially for deep tumors due to its low tissue penetration restriction. The therapeutic efficacy of SDT is limited due to the complicated tumor microenvironment. This study reports the construction of oxygen-carrying semiconducting polymer nanoprodrugs (OSPNpro) for deep tumor treatment via combining amplified SDT with pyroptosis. An oxygen carrier perfluorohexane, sonodynamic semiconducting polymer as the sonosensitizer, and reactive oxygen species (ROS)-responsive prodrug are co-loaded into a nanoparticle system, leading to the formation of these polymer nanoprodrugs. Such OSPNpro show an effective accumulation in tumor tissues after systemic administration, in which they deliver oxygen to relieve tumor hypoxia microenvironment and thus mediate amplified SDT via producing ROS under ultrasound (US) irradiation, even when the tumors are covered with a 2-cm chicken breast tissue. In addition, the ROS-responsive prodrugs are activated by the generated ROS to trigger pyroptosis of tumor cells. Such a sono-pyroptosis induces a strong antitumor immunity with obviously higher level infiltrations of effector immune cells into tumors. Therefore, OSPNpro-based combinational therapy can greatly inhibit the growth of 2-cm chicken breast tissue-covered deep tumors and suppress tumor metastasis. This study offers a prodrug nanoplatform for treatment of deep tumor via sono-pyroptosis strategy.

Abstract Image

载氧半导体聚合物纳米药物诱导声突变,用于深层组织肿瘤治疗
声动力疗法(SDT)一直被探索用于癌症治疗,尤其是对深部肿瘤的治疗,因为其组织穿透限制较低。由于肿瘤微环境复杂,声动力疗法的疗效有限。本研究报告了通过将放大 SDT 与热渗透相结合,构建用于深部肿瘤治疗的载氧半导体聚合物纳米药物(OSPNpro)。氧载体全氟己烷、声动力学半导体聚合物作为声敏化剂,以及活性氧(ROS)响应原药被共同负载到一个纳米粒子系统中,从而形成了这种聚合物纳米药物。这种 OSPNpro 在全身给药后可在肿瘤组织中有效积累,即使肿瘤被 2 厘米厚的鸡胸组织覆盖,它们也能在超声(US)照射下产生 ROS,为缓解肿瘤缺氧微环境提供氧气,从而介导 SDT 放大。此外,ROS 反应原药会被产生的 ROS 激活,引发肿瘤细胞的热凋亡。这种超氧化物酶诱导了强大的抗肿瘤免疫力,效应免疫细胞对肿瘤的浸润水平明显提高。因此,基于 OSPNpro 的联合疗法可以极大地抑制 2 厘米鸡乳腺组织覆盖的深部肿瘤的生长,并抑制肿瘤转移。这项研究为通过声波-突变策略治疗深部肿瘤提供了一个原药纳米平台。
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CiteScore
17.20
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