PEI-Based Nanoparticles for Tumor Immunotherapy via In Situ Antigen-Capture Triggered by Photothermal Therapy

Abstract

Activating a tumor antigen-specific immune response is key to the success of tumor immunotherapy and the development of personalized antitumor therapy. Nanocarriers can capture, enrich, and protect in situ produced tumor antigens due to immunogenic cell death (ICD), thus enhancing the tumor-specific immune response. Developing multifunctional nanocarriers that combine multiple antigen capturing mechanisms is crucial to the activation of tumor-specific immune responses. In this study, polyethylenimine (PEI) was employed as a main building block to construct a series of multifunctional indocyanine green (ICG)-loaded nanoparticles to capture antigens via multiple mechanisms: electrostatic interactions with PEI, hydrophobic interactions with the thermosensitive segment (POEGMA300), and covalent bonding with the pyridyl disulfide (PDS) groups, respectively. Their capacity of ICD induction, tumor antigen-capture, and antitumor immune responses were evaluated. Both the intrinsic toxicity of PEI and the ICG-mediated photothermal effect were responsible for inducing ICD. The positively charged PEI segment exhibited the best antigen-capturing ability via electrostatic interactions, promoted bone marrow-derived dendritic cell maturation and CD8+ T cell proliferation, and elicited antitumor immune responses in vivo. PDS groups bonded antigens covalently and significantly contributed to the suppression of distant tumor growth. Although the thermosensitive hydrophobic polymer segment did not contribute positively to antigen capture or tumor growth inhibition, NPs containing all of the functional modules prolonged the survival of tumor-bearing mice more than other treatments. This study provides more chemical insights into the design of polymer-based in situ nanovaccines against cancer.

Nanoparticles in tumor microenvironment remodeling and cancer immunotherapy

“…Then, T cells are activated and improve the potential PD-L1 blockade in cancer immunotherapy [ 404 ]. For stimulation of ICD, various kinds of nanoparticles including polymeric nanostructures [ 405 , 406 ], liposome-modified polysopamine structures [ 407 ], cRGD-functionalized TPGS nanoparticles [ 408 ], iron (II)-cytosine-phosphate-guanine nanoparticles [ 297 ] and iron oxide nanostructures [ 409 ] have been introduced to enhance cancer immunotherapy. Therefore, nanoparticle-mediated ICD can cause stimulation of dendritic cells to activate T cells in lymph nodes for increasing cancer immunotherapy.…”

Advanced Strategies for Strengthening the Immune Activation Effect of Traditional Antitumor Therapies

“…With the ingenious combination of ICB therapy and PTT-mediated immune activation, AZ-P@P exhibited excellent inhibition of both orthotopic and metastatic tumors. Additionally, apart from the Au-based nanoparticles, other nanomaterials carrying specific chemical groups or positive charge can also be employed to capture the tumor antigens during TTS-involved immune regulation, since antigen proteins are easy to bind with these nanoparticles via chemical or physical interactions. , Therefore, Chen et al selected the cationic polymer polyethylenimine (PEI) and the temperature-sensitive polymer poly[oligo (ethylene glycol) methacrylate] (POEGMA300) containing active pyridyl disulfide groups (PSD) to build an excellent antigen-capture nanodevice (ICG@PEI/LCST/PDS NPs) to magnify the immune activation effect of antitumor PTT (Figure B) . For this purpose, the cyclodextrin-modified PEI was assembled with the adamantane-conjugated POEGMA300 and PTT agent (indocyanine green, ICG) through a supramolecular interaction.…”

“…(B) The construction of ICG@PEI/LCST/PDS NPs for inducing tumor ICD effect via PTT and capturing tumor antigens to achieve significant immune activation for tumor. Reproduced from ref . Copyright 2023 American Chemical Society.…”