In vivo hitchhiking of immune cells by intracellular self-assembly of bacteria-mimetic nanomedicine for targeted therapy of melanoma

Abstract

Cell-based drug carriers are mostly prepared in vitro, which may negatively affect the physiological functions of cells, and induce possible immune rejections when applied to different individuals. In addition, the immunosuppressive tumor microenvironment limits immune cell–mediated delivery. Here, we report an in vivo strategy to construct cell-based nanomedicine carriers, where bacteria-mimetic gold nanoparticles (GNPs) are intravenously injected, selectively phagocytosed by phagocytic immune cells, and subsequently self-assemble into sizable intracellular aggregates via host-guest interactions. The intracellular aggregates minimize exocytosis of GNPs from immune cells and activate the photothermal property via plasmonic coupling effects. Phagocytic immune cells carry the intracellular GNP aggregates to melanoma tissue via inflammatory tropism. Moreover, an initial photothermal treatment (PTT) of the tumor induces tumor damage that subsequently provides positive feedback to recruit more immune cell–based carriers for enhanced targeting efficiency. The optimized secondary PTT notably improves antitumor immunotherapy, further strengthened by immune checkpoint blockade.

Tumor Acidic Microenvironment-Responsive Promodulator Iron Oxide Nanoparticles for Photothermal-Enhanced Chemodynamic Immunotherapy of Cancer

“…Due to the tumor-suppression effect, the therapeutic efficacy of sole therapeutic modality is often limited. Nanomedicines can be utilized to integrate various types of therapeutic modalities (such as photothermal therapy (PTT), chemotherapy, immunotherapy, and radiotherapy) into one single system to allow more effective antitumor therapy via combinational actions. − For example, PTT that uses photothermal agents and light conversion to generate heat has been widely combined with other therapeutic modalities for cancer therapy . To achieve complete tumor ablation via the PTT effect, high-power lasers are usually used to heat the tumor area to above 50 °C, but the painful treatment process and severe damage to healthy tissues during heating limit the practical applications of independent PTT .…”

Nanomaterials: small particles show huge possibilities for cancer immunotherapy

“…Moreover, OMVs enhance the infiltration of CTL and NK cells in tumor tissues, achieving a multifaceted anti-tumor effect [ 103 ]. Wang et al [ 104 ] proposed the use of OMVs to wrap β-CD and ADA-modified GNPs to obtain M-CD-GNPS and M-ADA-GNPs, respectively, which undergo degradation of OMVs under phagocytosis of immune cells and subsequently drive the self-assembly of GNPs under β-CD-ADA host–guest interactions. In vivo experiments, laser irradiation was administered for 5 min at 1 h and 4 h after tail vein injection of NPs, in concert with aPD-L1 treatment.…”

Cancer Stem Cells and the Tumor Microenvironment: Targeting the Critical Crosstalk through Nanocarrier Systems

“…Consequently, alternative means of targeting like TME modulation [232][233][234], and biological methods like cellular hitchhiking [235], extracellular vesicles [236][237][238], and even attenuated bacteria [239,240] are also prominently being considered as potential solutions to the above issue of NC delivery [241].…”