Advancing immune checkpoint blockade in colorectal cancer therapy with nanotechnology

Abstract

Immune checkpoint blockade (ICB) has gained unparalleled success in the treatment of colorectal cancer (CRC). However, undesired side effects, unsatisfactory response rates, tumor metastasis, and drug resistance still hinder the further application of ICB therapy against CRC. Advancing ICB with nanotechnology can be game-changing. With the development of immuno-oncology and nanomaterials, various nanoplatforms have been fabricated to enhance the efficacy of ICB in CRC treatment. Herein, this review systematically summarizes these recent nano-strategies according to their mechanisms. Despite their diverse and complex designs, these nanoplatforms have four main mechanisms in enhancing ICB: 1) targeting immune checkpoint inhibitors (ICIs) to tumor foci, 2) increasing tumor immunogenicity, 3) remodeling tumor microenvironment, and 4) pre-sensitizing immune systems. Importantly, advantages of nanotechnology in CRC, such as innovating the mode-of-actions of ICB, modulating intestinal microbiome, and integrating the whole process of antigen presentation, are highlighted in this review. In general, this review describes the latest applications of nanotechnology for CRC immunotherapy, and may shed light on the future design of ICB platforms.

In-situ formed thermosensitive hydrogel amplifies statin-mediated immune checkpoint blockade for coordinated tumor chemo-immunotherapy

“…The expression level of PD-L1 on CT26 cell surface upon ATO treatment was about 40% of untreated group ( Figure 2A ), indicating that ATO suppressed PD-L1 expression on colon cancers. It should be noted that CTX upregulated PD-L1 on CT26 cells ( Figure 2A ), which was in line with other chemotherapeutic drugs ( Liu et al, 2022a ; Liu et al, 2022b ). Compared with single treatment of CTX, treatment of CTX + ATO had a lower PD-L1 expression ( Figure 2A ), indicating that chemotherapy-induced PD-L1 upregulation could be reversed by statins.…”

“…Although many small molecule drugs and their combination with immune checkpoint blockade antibodies have proved clinical efficacy against solid tumors, one of the major limitations of these therapies is their rapid diffusion from the target tissue ( Zhuang et al, 2019 ; Liu et al, 2022a ; Liu et al, 2022b ). The incorporation of ICD-inducing chemotherapeutics and PD-L1-inhibiting drugs into a hydrogel drug delivery system is sufficient to overcome this difficulty and realize satisfactory tumor inhibition.…”

Noble Metal Nanoparticle-Based Photothermal Therapy: Development and Application in Effective Cancer Therapy

“…In recent years, immune checkpoint blockade therapy has solidified its position as a pivotal strategy in tumor immunotherapy. Monoclonal antibodies targeting checkpoint molecules, including programmed death receptor 1 (PD-1)/programmed death ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4), have received FDA approval and demonstrated success in clinical applications [ 69 , 70 ]. The emergence of these therapies marks a significant milestone in the field.…”