Protein corona (PC) formation confers novel biological properties to the original nanomaterial, impeding its uptake and targeting efficacy in cells and tissues. Although many studies discussing PC formation have focused on inert proteins that may inhibit the function of nanomaterials, some functional plasma proteins with intrinsic targeting capabilities can also be adsorbed to the surface of nanomaterials, with active ligand properties to improve the targeting ability. In this approach, nanomaterials are surface-engineered to promote the adsorption of specific functional plasma proteins that are directly targeted to transport nanomaterials to the target site. In this study, T₁₀ peptide-modified liposomes were employed to construct an in situ transferrin (Tf) PC-mediated liposome carrying a hypoxia-sensitive chemotherapy drug (tirapazamine, TPZ) and a photosensitizer (indocyanine green, IR820). The water-soluble drug TPZ was encapsulated in mesoporous silica nanoparticles (MSNs) and coated with IR820 (IR)-loaded liposome. Lipid-coated MSNs can inhibit aggregation in the body and significantly reduce the rapid release of water-soluble drugs, resulting in improved system stability and sustained release. Upon entering the in vivo circulation, T₁₀ bound specifically to Tf in plasma to form an in situ Tf liposome–PC complex with enhanced targeting efficacy compared to traditional ligand-modified active-targeting strategies. However, large-sized PC particles faced challenges in penetrating deep into tumor tissues. IR could kill tumors through photodynamic therapy (PDT) and elicit complementary antitumor effects with the hypoxia-sensitive drug TPZ. This study demonstrates the novel design of in situ PC-mediated multifunctional liposomes for hypoxia-activated chemotherapy combined with PDT, a promising approach to cancer therapy.

中文翻译：

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转铁蛋白 Corona 靶向替拉帕扎明和 IR820 的共同递送有助于 PDT 诱导的 4T1 乳腺癌高效低氧化疗


蛋白质电晕 （PC） 的形成赋予原始纳米材料新的生物学特性，阻碍其在细胞和组织中的摄取和靶向功效。尽管许多讨论 PC 形成的研究都集中在可能抑制纳米材料功能的惰性蛋白质上，但一些具有内在靶向能力的功能性等离子体蛋白也可以吸附到纳米材料表面，具有活性配体特性，以提高靶向能力。在这种方法中，纳米材料经过表面工程改造，以促进特定功能等离子体蛋白的吸附，这些等离子体蛋白直接靶向将纳米材料运输到目标位点。在这项研究中，采用 T₁₀ 肽修饰的脂质体构建原位转铁蛋白 （Tf） PC 介导的脂质体，该脂质体携带缺氧敏感的化疗药物 （tirapazamine， TPZ） 和光敏剂 （吲哚菁绿， IR820）。将水溶性药物 TPZ 封装在介孔二氧化硅纳米颗粒 （MSN） 中，并涂有载有 IR820 （IR） 脂质体。脂质包被的 MSNs 可以抑制体内的聚集，并显着减少水溶性药物的快速释放，从而提高系统稳定性和持续释放。进入体内循环后，T₁₀ 与血浆中的 Tf 特异性结合，形成原位 Tf 脂质体-PC 复合物，与传统的配体修饰的主动靶向策略相比，具有增强的靶向效力。然而，大尺寸 PC 颗粒在深入肿瘤组织方面面临挑战。IR 可以通过光动力疗法 （PDT） 杀死肿瘤，并与缺氧敏感药物 TPZ 产生互补的抗肿瘤作用。 本研究展示了原位 PC 介导的多功能脂质体用于缺氧激活化疗联合 PDT 的新设计，这是一种很有前途的癌症治疗方法。