Engineering nanoparticles to reprogram radiotherapy and immunotherapy: recent advances and future challenges

Abstract

Nanoparticles (NPs) have been increasingly studied for radiosensitization. The principle of NPs radio-enhancement is to use high-atomic number NPs (e.g. gold, hafnium, bismuth and gadolinium) or deliver radiosensitizing substances, such as cisplatin and selenium. Nowadays, cancer immunotherapy is emerged as a promising treatment and immune checkpoint regulation has a potential property to improve clinical outcomes in cancer immunotherapy. Furthermore, NPs have been served as an ideal platform for immunomodulator system delivery. Owing to enhanced permeability and retention (EPR) effect, modified-NPs increase the targeting and retention of antibodies in target cells. The purpose of this review is to highlight the latest progress of nanotechnology in radiotherapy (RT) and immunotherapy, as well as combining these three strategies in cancer treatment. Overall, nanomedicine as an effective strategy for RT can significantly enhance the outcome of immunotherapy response and might be beneficial for clinical transformation.

Keywords: Immune checkpoint blockade therapy; Immunotherapy; Nanoparticles; Radiotherapy.

Fig. 1

Schematic of nanoparticle functional mechanisms in radiotherapy. Combing ionizing radiation (IR) with nanoparticles (NPs) can boost radiosensitization, cell apoptosis and cytotoxicity. Upper: Metallic NPs (Au, Hf, Gd and Bi) deposit the IR dose through interactions, such as electron secretion (Compton, Auger and photoelectric), ROS generation and energy amplification. Down: Non-metallic NPs-encapsulated combined with radiotherapy further induced DNA damage and prevented rapid DNA repair, which will cause more cell apoptosis

Fig. 2

Targeting immunomodulators to immune cells in tumor microenvironment (TME). a Strategies for the application of NPs in immune checkpoint blockade therapy: NP-encapsulated immune checkpoint inhibitors and PD-L1 siRNA (Node 1 and 2), NP-encapsulated different drugs combined with immune checkpoint inhibitors (Node 3 and 4). The particles carried the target modulator, which further targeted the epitopes on immune cells, and direct or indirect antitumor action. b NPs extravasate into the tumor stroma through the fenestrations of the angiogenic vasculature, which can be enhanced by the EPR effect. c NPs have ability to carry one or more therapeutic agent to modulate T cells activation. Upper: Category of NP assembly; Lower: Different therapeutic payload

Fig. 3

Representation of the nanoparticle and radiotherapy in systemic antitumor immunity. Three types of NPs (BNP, ANPs and PLGA-R837/Cat) combined with radiotherapy can promote the tumor associated antigen secretion, anti-tumor cytokines secretion and systemic immunity. The function of NPs not only stimulated the DCs and T cells activation, but also suppressed the tumor malignant immune cells such as Tregs and macrophages