Self-carried nanodrug (SCND-SIS3) : A targeted therapy for lung cancer with superior biocompatibility and immune boosting effects

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

  • Guang-Yu Lian
  • Thomas Shiu-Kwong Mak
  • Qing-Ming Wang
  • Jiaoyi Chen
  • Zi-Ying Wang
  • Min Li
  • Patrick Ming-Kuen Tang
  • Xiao-Ru Huang
  • Xue-Qing Yu
  • Hui-Yao Lan

Detail(s)

Original languageEnglish
Article number121730
Journal / PublicationBiomaterials
Volume288
Online published12 Aug 2022
Publication statusPublished - Sep 2022

Link(s)

Abstract

Transforming growth factor β (TGF-β) is a well-known key mediator for the progression and metastasis of lung carcinoma. However, cost-effective anti-TGF-β therapeutics for lung cancer remain to be explored. Specifically, the low efficacy in drug delivery greatly limits the clinical application of small molecular inhibitors of TGF-β. In the present study, specific inhibitor of Smad3 (SIS3) is developed into a self-carried nanodrug (SCND-SIS3) using the reprecipitation method, which largely improves its solubility and bioavailability while reduces its nephrotoxicity. Compared to unmodified-SIS3, SCND-SIS3 demonstrates better anti-cancer effects through inducing tumor cell apoptosis, inhibiting angiogenesis, and boosting NK cell-mediated immune responses in syngeneic Lewis Lung Cancer (LLC) mouse model. Better still, it could achieve comparable anti-cancer effect with just one-fifth the dose of unmodified-SIS3. Mechanistically, RNA-sequencing analysis and cytokine array results unveil a TGF-β/Smad3-dependent immunoregulatory landscape in NK cells. In particular, SCND-SIS3 promotes NK cell cytotoxicity by ameliorating Smad3-mediated transcriptional inhibition of Ndrg1. Furthermore, improved NK cell cytotoxicity by SCND-SIS3 is associated with higher expression of activation receptor Nkp46, and suppressed levels of Trib3 and TSP1 as compared with unmodified-SIS3. Taken together, SCND-SIS3 possesses superior anti-cancer effects with enhanced bioavailability and biocompatibility, therefore representing as a novel therapeutic strategy for lung carcinoma with promising clinical potential.

Research Area(s)

  • Lung carcinoma, NK-mediated immune responses, Self-carried nanodrug, SIS3, TGF-β/Smad3 signaling, Tumor-targeting therapy

Citation Format(s)

Self-carried nanodrug (SCND-SIS3) : A targeted therapy for lung cancer with superior biocompatibility and immune boosting effects. / Lian, Guang-Yu; Wan, Yingpeng; Mak, Thomas Shiu-Kwong; Wang, Qing-Ming; Zhang, Jinfeng; Chen, Jiaoyi; Wang, Zi-Ying; Li, Min; Tang, Patrick Ming-Kuen; Huang, Xiao-Ru; Lee, Chun-Sing; Yu, Xue-Qing; Lan, Hui-Yao.

In: Biomaterials, Vol. 288, 121730, 09.2022.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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