Recyclable Cytokines on Short and Injectable Polylactic Acid Fibers for Enhancing T-Cell Function

Hyun Mu Shin, Youngjun Ju, Gwanghun Kim, Jae Won Lee, Myung Won Seo, Ji Hyun Sim, Jusang Yang, Sora Noh, Jungbae Kim, Hang Rae Kim

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

The current practice of cytokine-based immunotherapy relies on high doses and multiple injections of cytokine agents, which raises patients' inconvenience and economic burden. Here, sustainable and recyclable cytokine delivery based on short and injectable polymer fibers immobilized with interleukin (IL)-2 and IL-15 is demonstrated, which can be retained at the target tumor sites upon injection. In detail, electrospun polylactic acid (PLA) fibers are treated with aqueous ethanol solution for their dispersion, increasing the interfiber space for highly efficient biomolecule conjugation, and further immobilized with protein G via enzymatic dopamine coating. The protein G-immobilized PLA fibers are cut into short fibers using a microtome, and filtering is performed to collect injectable short PLA (sPLA) fibers with the lengths of 15–100 µm. These sPLA fibers are further loaded with cytokines via the interaction between protein G and Fc, and cytokine-loaded sPLA (Cyto-sPLA) fibers are injected near the tumor sites using a syringe. The administration of Cyto-sPLA fibers efficiently suppresses the tumor growth up to 70% by reinvigorating nonfunctional T cells to a functional state that can kill tumors in a sustainable and recyclable manner. The injectable sPLA-fiber platform can be employed as a carrier for the efficient delivery of various agents in vivo.

Original languageEnglish
Article number1808361
JournalAdvanced Functional Materials
Volume29
Issue number14
DOIs
Publication statusPublished - 2019 Apr 4

Bibliographical note

Funding Information:
H.M.S. and Y.J. contributed equally to this work. This work was supported in part by the Creative-Pioneering Researchers Program through SNU (to H.-R.K.), Nano-Material Technology Development Program (2014M3A7B4052192 to J.K. and H.-R.K.), and Global Research Laboratory Program (2014K1A1A2043032 to J.K.) through the National Research Foundation of Korea (NRF), and the NRF Grant funded by the Korean Government (MOE) (2017R1A4A1015745 to H.-R.K.). The authors acknowledge Young Hyeon Kwon and Bum Chul Park for their help in preparing nanofibers.

Publisher Copyright:
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

  • cancer immunotherapy
  • cytokine delivery
  • electrospun fibers
  • enzymatic polydopamine coating
  • injectable fibers

ASJC Scopus subject areas

  • General Chemistry
  • General Materials Science
  • Condensed Matter Physics

Fingerprint

Dive into the research topics of 'Recyclable Cytokines on Short and Injectable Polylactic Acid Fibers for Enhancing T-Cell Function'. Together they form a unique fingerprint.

Cite this