Overcoming Cytosolic Delivery Barriers of Proteins Using Denatured Protein-Conjugated Mesoporous Silica Nanoparticles

Julien Dembélé, Jou Hsuan Liao, Tsang Pai Liu, Yi Ping Chen

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Intracellular delivery of therapeutic proteins has increased advantages over current small-molecule drugs and gene therapies, especially in therapeutic efficacies for a broad spectrum of diseases. Hence, developing the protein therapeutics approach provides a needed alternative. Here, we designed a mesoporous silica nanoparticle (MSN)-mediated protein delivery approach and demonstrated effective intracellular delivery of the denatured superoxide dismutase (SOD) protein, overcoming the delivery challenges and achieving higher enzymatic activity than native SOD-conjugated MSNs. The denatured SOD-conjugated MSN delivery strategy provides benefits of reduced size and steric hindrance, increased protein flexibility without distorting its secondary structure, exposure of the cell-penetrating peptide transactivator of transcription for enhanced efficient delivery, and a change in the corona protein composition, enabling cytosolic delivery. After delivery, SOD displayed a specific activity around threefold higher than in our previous reports. Furthermore, the in vivo biosafety and therapeutic potential for neuron therapy were evaluated, demonstrating the biocompatibility and the effective antioxidant effect in Neuro-2a cells that protected neurite outgrowth from paraquat-induced reactive oxygen species attack. This study offers an opportunity to realize the druggable possibility of cytosolic proteins using MSNs.

Original languageEnglish
Pages (from-to)432-451
Number of pages20
JournalACS Applied Materials and Interfaces
Volume15
Issue number1
DOIs
Publication statusPublished - Jan 2023

Keywords

  • mesoporous silica nanoparticles
  • protein corona
  • protein delivery
  • size/steric hindrance
  • surface functionalization
  • TAT peptide

ASJC Scopus subject areas

  • General Materials Science

Fingerprint

Dive into the research topics of 'Overcoming Cytosolic Delivery Barriers of Proteins Using Denatured Protein-Conjugated Mesoporous Silica Nanoparticles'. Together they form a unique fingerprint.

Cite this