NIR Light and GSH Dual-Responsive Upconversion Nanoparticles Loaded with Multifunctional Platinum(IV) Prodrug and RGD Peptide for Precise Cancer Therapy,ACS Applied Materials & Interfaces

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NIR Light and GSH Dual-Responsive Upconversion Nanoparticles Loaded with Multifunctional Platinum(IV) Prodrug and RGD Peptide for Precise Cancer Therapy
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2024-07-24 , DOI: 10.1021/acsami.4c08899
Xiao-Meng Liu ₁ , Zhen-Zhen Zhu ₁ , Xin-Rui He ₁ , Yun-Hong Zou ₁ , Qian Chen ₁ , Xiao-Ya Wang ₁ , Hui-Mei Liu ₁ , Xin Qiao ₁ , Xu Wang ₁ , Jing-Yuan Xu _{1,

2}

Affiliation

Platinum(II) drugs as a first-line anticancer reagent are limited by side effects and drug resistance. Stimuli-responsive nanosystems hold promise for precise spatiotemporal manipulation of drug delivery, with the aim to promote bioavailability and minimize side effects. Herein, a multitargeting octahedral platinum(IV) prodrug with octadecyl aliphatic chain and histone deacetylase inhibitor (phenylbutyric acid, PHB) at axial positions to improve the therapeutic effect of cisplatin was loaded on the upconversion nanoparticles (UCNPs) through hydrophobic interaction. Followed attachment of DSPE-PEG₂₀₀₀ and arginine-glycine-aspartic (RGD) peptide endowed the nanovehicles with high biocompatibility and tumor specificity. The fabricated nanoparticles (UCNP/Pt(IV)-RGD) can be triggered by upconversion luminescence (UCL) irradiation and glutathione (GSH) reduction to controllably release Pt(II) species and PHB, inducing profound cytotoxicity. Both in vitro and in vivo experiments demonstrated that UCNP/Pt(IV)-RGD exhibited remarkable antitumor efficiency, high tumor-targeting specificity, and real-time UCL imaging capacity, presenting an intelligent platinum(IV) prodrug-loaded nanovehicle for UCL-guided dual-stimuli-responsive combination therapy.

中文翻译：

载有多功能铂 (IV) 前药和 RGD 肽的近红外光和谷胱甘肽双响应上转换纳米粒子，用于精准癌症治疗

铂(II)药物作为一线抗癌试剂受到副作用和耐药性的限制。刺激响应纳米系统有望实现药物输送的精确时空操纵，旨在提高生物利用度并最大限度地减少副作用。在此，通过疏水相互作用将具有十八烷基脂肪链和组蛋白脱乙酰酶抑制剂（苯基丁酸，PHB）的多靶点八面体铂（IV）前药负载在上转换纳米颗粒（UCNP）上，以提高顺铂的治疗效果。随后附着 DSPE-PEG ₂₀₀₀和精氨酸-甘氨酸-天冬氨酸 (RGD) 肽，赋予纳米载体高生物相容性和肿瘤特异性。所制造的纳米粒子（UCNP/Pt(IV)-RGD）可以通过上转换发光（UCL）照射和谷胱甘肽（GSH）还原来触发，以可控地释放Pt（II）物质和PHB，从而诱导严重的细胞毒性。体外和体内实验表明，UCNP/Pt(IV)-RGD具有显着的抗肿瘤效率、高肿瘤靶向特异性和实时UCL成像能力，为UCL提供了一种智能的铂(IV)前药负载纳米载体。引导双刺激响应联合治疗。

更新日期：2024-07-24

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