Tumor-Homing and Immune-Reprogramming Cellular Nanovesicles for Photoacoustic Imaging-Guided Phototriggered Precise Chemoimmunotherapy

Abstract

Many studies have focused on developing effective therapeutic strategies to selectively destroy primary tumors, eliminate metastatic lesions, and prevent tumor recurrence with minimal side effects on normal tissues. In this work, we synthesized engineered cellular nanovesicles (ECNVs) with tumor-homing and immune-reprogramming functions for photoacoustic (PA) imaging-guided precision chemoimmunotherapy. M1-macrophage-derived cellular nanovesicles (CNVs) were loaded with gold nanorods (GNRs), gemcitabine (GEM), CpG ODN, and PD-L1 aptamer. The good histocompatibility and tumor-homing effect of CNVs improved drug retention in the bloodstream and led to their enrichment in tumor tissues. Furthermore, the photothermal ability of GNRs enabled PA imaging-guided drug release. GEM induced tumor immunogenic cell death (ICD), and CpG ODN promoted an immune response to the antigens released by ICD, leading to long-term specific antitumor immunity. In addition, the PD-L1 aptamer relieved the inhibitory effect of the PD1/PD-L1 checkpoint on CD8+ T-cells and augmented the immunotherapeutic effect. The synergistic innate and adaptive immune responses enhanced the antitumor effect of ECNVs. In summary, this nanoplatform integrates local targeted photothermal therapy with extensive progressive chemotherapy and uses ICD to reshape the immune microenvironment for tumor ablation.

Biomimetic Active Materials Guided Immunogenic Cell Death for Enhanced Cancer Immunotherapy

“…[ 62 ] The unique advantages of M1‐macrophage derived CNVs have been used for delivery ICD‐inducer gemcitabine (GEM) for tumor ICD and transformation of TME from “cold” to “hot” (Figure 5B), guiding a long‐term specific antitumor immunity and realizing precise combination therapy of ICB and chemoimmunotherapy. [ 63 ] Thus, above mentioned studies has evidenced that cellular vesicles biomimetic nanoagents are able to guide ICD progress with long‐circulating, tumor‐targeting capability, and ability of regulating the TME.…”

Upconversion Nanoplatform Enables Multimodal Imaging and Combinatorial Immunotherapy for Synergistic Tumor Treatment and Monitoring

“…12 Currently, treatment with anti-PD-L1 antibody (αPD-L1), designed for immune checkpoint blockade (ICB) therapy, constitutes a promising antitumor immunotherapy. 13 Therefore, we hypothesized that PTT−chemotherapy combined with ICB therapy can afford vigorous OSCC curative potential.…”

“…Among them, programmed cell death 1 ligand 1 (PD-L1) interacts with programmed cell death receptor 1 (PD-1), inducing T-cell apoptosis and immune escape . Currently, treatment with anti-PD-L1 antibody (αPD-L1), designed for immune checkpoint blockade (ICB) therapy, constitutes a promising antitumor immunotherapy . Therefore, we hypothesized that PTT–chemotherapy combined with ICB therapy can afford vigorous OSCC curative potential.…”

Mild photothermal/radiation therapy potentiates ferroptosis effect for ablation of breast cancer via MRI/PA imaging guided all-in-one strategy

“…[ 24 ]. In past decade, ferroptosis, an iron- and reactive oxygen species (ROS)-dependent form of PCD [ 25 , 26 ], has attracted much attention and exploration in the cancer therapeutic mechanism of various nano-theranostics agents [ 27 ]. Among most of the reported nanomaterials, FePt and Fe 3 O 4 NPs can reach the tumor area via enhanced permeability and retention (EPR) targeting effect.…”