Protein-nanoparticle co-assembly supraparticles for drug delivery: Ultrahigh drug loading and colloidal stability, and instant and complete lysosomal drug release

Zixing Xu, Huoyue Lin, Jie Dai, Xiaowei Wen, Xiaoya Yu, Can Xu*, Gang Ruan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Two frequent problems hindering clinical translation of nanomedicine are low drug loading and low colloidal stability. Previous efforts to achieve ultrahigh drug loading (>30 %) introduce new hurdles, including lower colloidal stability and others, for clinical translation. Herein, we report a new class of drug nano-carriers based on our recent finding in protein-nanoparticle co-assembly supraparticle (PNCAS), with both ultrahigh drug loading (58 % for doxorubicin, i.e., DOX) and ultrahigh colloidal stability (no significant change in hydrodynamic size after one year). We further show that our PNCAS-based drug nano-carrier possesses a built-in environment-responsive drug release feature: once in lysosomes, the loaded drug molecules are released instantly (<1 min) and completely (∼100 %). Our PNCAS-based drug delivery system is spontaneously formed by simple mixing of hydrophobic nanoparticles, albumin and drugs. Several issues related to industrial production are studied. The ultrahigh drug loading and stability of DOX-loaded PNCAS enabled the delivery of an exceptionally high dose of DOX into a mouse model of breast cancer, yielding high efficacy and no observed toxicity. With further developments, our PNCAS-based delivery systems could serve as a platform technology to meet the multiple requirements of clinical translation of nanomedicines.

Original languageEnglish
Article number124231
JournalInternational Journal of Pharmaceutics
Volume658
DOIs
Publication statusPublished - 10 Jun 2024
Externally publishedYes

Keywords

  • Assembly
  • Cancer
  • Environment-responsive release
  • Nanomedicine
  • Production
  • Translation

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