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一种具有可切换药物释放功能的可注射热纳米纤维网,以增强化疗效果。

An injectable hyperthermic nanofiber mesh with switchable drug release to stimulate chemotherapy potency.

作者信息

Chen Lili, Fujisawa Nanami, Takanohashi Masato, Ebara Mitsuhiro

机构信息

Research Center for Functional Materials, National Institute for Materials Science (NIMS), Tsukuba, Japan.

Graduate School of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Japan.

出版信息

Front Bioeng Biotechnol. 2022 Nov 3;10:1046147. doi: 10.3389/fbioe.2022.1046147. eCollection 2022.

Abstract

We developed a smart nanofiber mesh (SNM) with anticancer abilities as well as injectability and fast recovery from irregular to non-compressible shapes. The mesh can be injected at the tumor site to modulate and control anticancer effects by loading the chemotherapeutic drug, paclitaxel (PTX), as well as magnetic nanoparticles (MNPs). The storage modulus of the mesh decreases when applied with a certain shear strain, and the mesh can pass through a 14-gauge needle. Moreover, the fibrous morphology is maintained even after injection. In heat-generation measurements, the mesh achieved an effective temperature of mild hyperthermia (41-43°C) within 5 min of exposure to alternating magnetic field (AMF) irradiation. An electrospinning method was employed to fabricate the mesh using a copolymer of -isopropylacrylamide (NIPAAm) and N-hydroxyethyl acrylamide (HMAAm), whose phase transition temperature was adjusted to a mildly hyperthermic temperature range. Pplyvinyl alcohol (PVA) was also incorporated to add shear-thinning property to the interactions between polymer chains derived from hydrogen bonding, The "on-off" switchable release of PTX from the mesh was detected by the drug release test. Approximately 73% of loaded PTX was released from the mesh after eight cycles, whereas only a tiny amount of PTX was released during the cooling phase. Furthermore, hyperthermia combined with chemotherapy after exposure to an AMF showed significantly reduced cancer cell survival compared to the control group. Subsequent investigations have proven that a new injectable local hyperthermia chemotherapy platform could be developed for cancer treatment using this SNM.

摘要

我们开发了一种具有抗癌能力、可注射性且能从不规则形状快速恢复到不可压缩形状的智能纳米纤维网(SNM)。该网可注射到肿瘤部位,通过负载化疗药物紫杉醇(PTX)以及磁性纳米颗粒(MNP)来调节和控制抗癌效果。当施加一定的剪切应变时,该网的储能模量会降低,并且可以通过14号针。此外,即使在注射后,纤维形态也能保持。在发热测量中,该网在暴露于交变磁场(AMF)照射5分钟内达到了轻度热疗(41 - 43°C)的有效温度。采用静电纺丝法,使用N - 异丙基丙烯酰胺(NIPAAm)和N - 羟乙基丙烯酰胺(HMAAm)的共聚物制备该网,其相变温度被调节到轻度热疗温度范围。还加入了聚乙烯醇(PVA),以通过氢键在聚合物链之间的相互作用增加剪切变稀特性。通过药物释放测试检测到PTX从该网中“开 - 关”可切换释放。在八个循环后,约73%负载的PTX从该网中释放,而在冷却阶段仅释放少量PTX。此外,与对照组相比,暴露于AMF后热疗联合化疗显示癌细胞存活率显著降低。后续研究证明,使用这种SNM可以开发一种用于癌症治疗的新型可注射局部热化疗平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fe1/9669589/eb89fd1a0300/FBIOE_fbioe-2022-1046147_wc_sch1.jpg

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