Department of Biomedical Engineering, Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, PO Box 513, 5600 MB, Eindhoven, The Netherlands.
Department of Medical BioScience, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, Geert Grooteplein 28, 6525 GA, Nijmegen, The Netherlands.
Angew Chem Int Ed Engl. 2023 Jun 12;62(24):e202300511. doi: 10.1002/anie.202300511. Epub 2023 May 8.
We describe here a near infrared light-responsive elastin-like peptide (ELP)-based targeted nanoparticle (NP) that can rapidly switch its size from 120 to 25 nm upon photo-irradiation. Interestingly, the targeting function, which is crucial for effective cargo delivery, is preserved after transformation. The NPs are assembled from (targeted) diblock ELP micelles encapsulating photosensitizer TT1-monoblock ELP conjugates. Methionine residues in this monoblock are photo-oxidized by singlet oxygen generated from TT1, turning the ELPs hydrophilic and thus trigger NP dissociation. Phenylalanine residues from the diblocks then interact with TT1 via π-π stacking, inducing the re-formation of smaller NPs. Due to their small size and targeting function, the NPs penetrate deeper in spheroids and kill cancer cells more efficiently compared to the larger ones. This work could contribute to the design of "smart" nanomedicines with deeper penetration capacity for effective anticancer therapies.
我们在这里描述了一种近红外光响应的弹性蛋白样肽（ELP）为基础的靶向纳米粒子（NP），它可以在光照射下迅速将其尺寸从 120nm 切换到 25nm。有趣的是，在转变后，靶向功能（这对有效货物输送至关重要）得以保留。这些 NP 由（靶向）二嵌段 ELP 胶束组装而成，其中封装了光敏剂 TT1-单嵌段 ELP 缀合物。该单嵌段中的蛋氨酸残基被 TT1 产生的单线态氧氧化，使 ELPs 亲水，从而触发 NP 解离。然后，二嵌段中的苯丙氨酸残基通过π-π 堆积与 TT1 相互作用，诱导更小 NP 的重新形成。由于其较小的尺寸和靶向功能，与较大的 NP 相比，NP 可以更深地穿透球体并更有效地杀死癌细胞。这项工作可能有助于设计具有更深穿透能力的“智能”纳米药物，以实现有效的抗癌治疗。
