Natural discoidal lipoproteins with tiny modification for tumor extracellular dissociation in antitumor chemoimmunotherapy

Huaqing Zhang, Hao Cheng, Yue Han, Yi Jin, Gang Wang, Chenhua Sun, Wenxin Jiang, Guochen Han, Bo Sun, Zijun Jiang, Zhou Yuan, Jianping Zhou, Yang Ding

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Appealing cancer immunotherapy requires synchronous presentation of tumor antigens and immunoadjuvant. Herein, a “one-step” modification strategy is proposed to tinily remould endogenous discoidal high density lipoprotein (dHDL) for tumor-homing and site-specific chemoimmunotherapy. For molecular targeting therapy, lipophilic immunoadjuvant CpG oligodeoxynucleotides is conjugated to facilitate HDL-surface anchoring; and GC nucleotides provide enough reservoir for completion of doxorubicin (Dox) “sandwich”. After administration, the tiny size (~30 nm) of disc nanodrug can maneuver deeply into tumors for receptor binding and in situ structural collapse. The intracellular concentrated CpG-Dox induce potent immunogenic cell death from burst Dox liberation at acidic pH. In turn, the released antigens and CpG motifs are simultaneously recognized by dendritic cells for antigen presentation and antitumor T cell responses. Combination chemoimmunotherapy with discoidal nanodrugs performed highest tumor weight inhibitory of 93.2% and extend the median survival time at a safe level. Collectively, this study suggests that the minimalist revolution of natural dHDL particulates may provide a biomimicry nanoplatform for site-specific amplified chemoimmunotherapy.

Original languageEnglish (US)
Article number120859
JournalBiomaterials
Volume275
DOIs
StatePublished - Aug 2021
Externally publishedYes

Keywords

  • Chemoimmunotherapy
  • CpG oligodeoxynucleotides
  • Natural discoidal lipoprotein
  • Site-specific collapse
  • “One step” modification strategy

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Ceramics and Composites
  • Biomaterials
  • Mechanics of Materials

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