Nanotechnology-enabled immunogenic cell death for improved cancer immunotherapy

Abstract

Tumor immunotherapy has revolutionized the field of oncology treatments in recent years. As one of the promising strategies of cancer immunotherapy, tumor immunogenic cell death (ICD) has shown significant potential for tumor therapy. Nanoparticles are widely used for drug delivery due to their versatile characteristics, such as stability, slow blood elimination, and tumor-targeting ability. To increase the specificity of ICD inducers and improve the efficiency of ICD induction, functionally specific nanoparticles, such as liposomes, nanostructured lipid carriers, micelles, nanodiscs, biomembrane-coated nanoparticles and inorganic nanoparticles have been widely reported as the vehicles to deliver ICD inducers in vivo. In this review, we summarized the strategies of different nanoparticles for ICD-induced cancer immunotherapy, and systematically discussed their advantages and disadvantages as well as provided feasible strategies for solving these problems. We believe that this review will offer some insights into the design of effective nanoparticulate systems for the therapeutic delivery of ICD inducers, thus, promoting the development of ICD-mediated cancer immunotherapy.

Keywords: Drug delivery; Nanoparticles; Tumor immunogenic cell death; Tumor immunotherapy.

Fig. 1

Schematic illustration of targeted ICD inducer (DOX) and IDO1 siRNA co-delivery system via anti-CD44/PD-L1 aptamer-conjugated liposome for synergistic chemoimmunotherapy. Adapted with permission from ref [97].

Fig. 2

A nanostructured lipid carrier (NLC) containing the immunogenic cell death inducer pirarubicin (THP) combined with tumor penetrating peptide(iRGD) can significantly inhibit tumor growth and increase immunogenic cell death. Adapted with permission from ref [107].

Fig. 3

The illustration of ATN-MPTX preparation (A) and chemo-immunotherapy of triple-negative breast cancer-bearing mice using α5β1 targeting ATN-MPTX and nano-STING agonist CPs-CDN (B). Adapted with permission from ref [82].

Fig. 4

Schematic of doxorubicin-loaded sHDL (sHDL-DOX) for chemo-immunotherapy. (A) sHDL-DOX is formulated by incubation of lipid-DOX with preformed sHDL. (B) The immune mechanism of sHDL-DOX in vivo. Adapted with permission from ref [125].

Fig. 5

Preparation procedure of cancer cell membrane–biomimetic nanoparticles. Extracting cancer MCF-7 cell membrane hybridized with PEGylated phospholipids (DSPE-PEG) and then coated onto ICG-loaded polymeric cores by extrusion. Adapted with permission from ref [131].

Fig. 6

The Schematic of serum albumin (SA) -coated boehmite (“ B “; Aluminum hydroxide) organic-inorganic scaffold (Ce6/MLT@SAB) loaded with dihydroporphyrin e6 (Ce6), photosensitizers and bee venom (MLT) peptide. Adapted with permission from ref [86].

Fig. 7

Schematic of the combination therapy AuNR/DOX gel under mild laser irradiation combined with antigen-capturing liposomes and anti-PD- PD-L1. Adapted with permission from ref [154].

Fig. 8

A schematic of the synthetic procedure of Se-MSN-PEG with cascading drug release and amplifying ICD manners and their application for efficient and safe cancer chemo-photo-immunotherapy. Adapted with permission from ref [164].

Fig. 9

Schematic depiction of NIR-mediated photothermal-immunotherapy with FNPs/rGO-PEG nanocomposites for destruction of primary tumors and eliciting an anti-metastatic effect [172].