Baculovirus Expressing Tumor Growth Factor-β1 (TGFβ1) Nanoshuttle Augments Therapeutic Effects for Vascular Wound Healing: Design and In Vitro Analysis.

IF 4.9 Q1 CHEMISTRY, MEDICINAL ACS Pharmacology and Translational Science Pub Date : 2024-10-25 eCollection Date: 2024-11-08 DOI:10.1021/acsptsci.4c00509

Paromita Islam, Ahmed Abosalha, Sabrina Schaly, Jacqueline L Boyajian, Madison Santos, Stephanie Makhlouf, Editha Renesteen, Amal Kassab, Cedrique Shum-Tim, Dominique Shum-Tim, Satya Prakash

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Abstract

One of the major challenges in vascular tissue regeneration is effective wound healing that can be resolved by an innovative targeted nanoshuttle that delivers growth factors to blood vessels. This study investigates the production and efficacy of transforming growth factor-β1 (TGFβ1) gene delivery using poly(lactic-co-glycolic acid) (PLGA) baculovirus (BV) nanoshuttles (NSs). They exhibited an encapsulation efficiency of 86.23% ± 0.65% and a negative zeta potential of -29.57 ± 1.27 mV. In vitro studies in human umbilical vein endothelial cells (HUVECs) revealed that a 12 h incubation period optimized virus transduction. The safety and superior intracellular uptake of NSs and BVs in HUVECs were observed. The NSs carrying 100 and 400 MOI exhibited the highest cell proliferation rates in HUVECs. These sustained-release NSs significantly improved vascular cell migration and wound closure compared to free TGFβ1 carrying BV and can be a groundbreaking find in regenerative medicine, cardiovascular diseases, and chronic ulcer conditions.

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表达肿瘤生长因子-β1（TGFβ1）的纳米树突状芽孢杆菌病毒增强了血管伤口愈合的治疗效果：设计与体外分析。

血管组织再生的主要挑战之一是有效的伤口愈合，而将生长因子输送到血管的创新型靶向纳米梭可以解决这一问题。本研究探讨了使用聚乳酸-共聚乙醇酸（PLGA）杆状病毒（BV）纳米套管（NSs）生产转化生长因子-β1（TGFβ1）基因递送产品及其功效。它们的封装效率为 86.23% ± 0.65%，负 zeta 电位为 -29.57 ± 1.27 mV。在人脐静脉内皮细胞（HUVECs）中进行的体外研究表明，12 小时的孵育期可优化病毒转导。在 HUVECs 中观察到了 NSs 和 BVs 的安全性和优异的细胞内吸收能力。100 和 400 MOI 的 NSs 在 HUVECs 中的细胞增殖率最高。与携带游离 TGFβ1 的 BV 相比，这些缓释 NSs 能明显改善血管细胞迁移和伤口闭合，是再生医学、心血管疾病和慢性溃疡领域的一项突破性发现。

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来源期刊

ACS Pharmacology and Translational Science Medicine-Pharmacology (medical)

CiteScore

10.00

自引率

3.30%

发文量

133

期刊介绍： ACS Pharmacology & Translational Science publishes high quality, innovative, and impactful research across the broad spectrum of biological sciences, covering basic and molecular sciences through to translational preclinical studies. Clinical studies that address novel mechanisms of action, and methodological papers that provide innovation, and advance translation, will also be considered. We give priority to studies that fully integrate basic pharmacological and/or biochemical findings into physiological processes that have translational potential in a broad range of biomedical disciplines. Therefore, studies that employ a complementary blend of in vitro and in vivo systems are of particular interest to the journal. Nonetheless, all innovative and impactful research that has an articulated translational relevance will be considered. ACS Pharmacology & Translational Science does not publish research on biological extracts that have unknown concentration or unknown chemical composition. Authors are encouraged to use the pre-submission inquiry mechanism to ensure relevance and appropriateness of research.