Combination of fucoidan-based magnetic nanoparticles and immunomodulators enhances tumour-localized immunotherapy

Abstract

Checkpoint immunotherapy that inhibits tumour immune evasion has demonstrated significant clinical success. However, the therapeutic response is limited to certain patient populations, and immunotoxicity as well as autoimmunity have compromised the therapeutic benefits. Here, we report on an inherently therapeutic fucoidan-dextran-based magnetic nanomedicine (IO@FuDex) conjugated with a checkpoint inhibitor (anti-PD-L1) and T-cell activators (anti-CD3 and anti-CD28). IO@FuDex can repair the immunosuppressive tumour microenvironment by reinvigorating tumour-infiltrating lymphocytes, while targeting the nanomedicine via magnetic navigation to the tumour to minimize off-target effects. Treatment that combines IO@FuDex and magnetic navigation reduces the occurrence of adverse events and extends the median survival from 32 to 63 days with less than 1 per cent dose compared with soluble anti-PD-L1. Thus, we demonstrate the potential of integrating anti-PD-L1 and T-cell activators as a form of inherently therapeutic nanomedicine to augment the therapeutic index of combination checkpoint immunotherapy.

Fucoidan-Based Theranostic Nanogel for Enhancing Imaging and Photodynamic Therapy of Cancer

“…Fucoidan is a natural biopolymer with a highly negative charge on a sulfated polysaccharide backbone. In recent years, fucoidan has attracted considerable interest due to its anticancer potential through various mechanisms such as the modulation of a scavenger receptor, metastasis blockade and immune system activation [9][10][11]. Fucoidan is also known to target the P-selectin, which is overexpressed on the surface of tumor neovascular endothelial cells as well as many other cancer cells [12][13][14].…”

Recent Advancements of Magnetic Nanomaterials in Cancer Therapy

“…Cancer immunotherapy covers the range of therapies that utilize the patient's own immune system to identify cancer cells, inhibit their proliferation, and even directly attack solid tumors. Multiple approaches have been taken to elicit immune responses for therapeutic effect, such as introducing inhibitory check point molecules (anti-CTLA-4 or anti-PD1/anti-PD-L1) [81], dendritic cell vaccines [82][83][84], adoptive cell transfer methods [85], or a combination of these approaches [86][87][88]. Combining cancer immunotherapy approaches with nanoparticles provides benefits such as a targeted delivery vehicle that can be precisely tuned to have the requisite size, shape, charge, and surface modifications to maximize delivery efficiency.…”

Immunomodulating Nanomedicine for Cancer Therapy

“…24 The magnetic core of the nanocomplex allowed in vivo magnetic navigation to improve tumor targeting and minimize off-target effect, while the simultaneous integration of PD-L1 inhibitor and T cell activator further augmented antitumor immune responses. 24 …”