Intratumoral immunotherapy using platelet-cloaked nanoparticles enhances antitumor immunity in solid tumors

Abstract

Intratumoral immunotherapy is an emerging modality for the treatment of solid tumors. Toll-like receptor (TLR) agonists have shown promise for eliciting immune responses, but systemic administration often results in the development of adverse side effects. Herein, we investigate whether localized delivery of the TLR agonist, resiquimod (R848), via platelet membrane-coated nanoparticles (PNP-R848) elicits antitumor responses. The membrane coating provides a means of enhancing interactions with the tumor microenvironment, thereby maximizing the activity of R848. Intratumoral administration of PNP-R848 strongly enhances local immune activation and leads to complete tumor regression in a colorectal tumor model, while providing protection against repeated tumor re-challenges. Moreover, treatment of an aggressive breast cancer model with intratumoral PNP-R848 delays tumor growth and inhibits lung metastasis. Our findings highlight the promise of locally delivering immunostimulatory payloads using biomimetic nanocarriers, which possess advantages such as enhanced biocompatibility and natural targeting affinities.

Development and Delivery Systems of mRNA Vaccines

“…The vaccine can induce strong and persistent anti PreS1 response and effectively eliminate the virus in mice with hepatitis B. Bahmani et al (2021) investigated the antitumor effect of resiquimod (R848), a delivery of TLR agonist, mediated by platelet membrane-coated nanoparticles (PNP). PNP can enhance the interaction between R848 and tumor, and maximize the activity of R848.…”

Macrophage polarization synergizes with oxaliplatin in lung cancer immunotherapy via enhanced tumor cell phagocytosis

“…Recently Bahmani B et al. emphasized that the local delivery of R848 loaded in nanoparticles resulted in total tumor regression via activating local immune responses in a colorectal tumor model [35] . Koh J et al.…”

TLR7/8-Agonist-Loaded M1-Macrophage-Derived Nanovesicles Promote the Polarization of Macrophages to Enhance Bladder Cancer Immunotherapy

“…The colloidal stability of M1 NV-R848 was investigated in PBS and serum at 37 °C by measuring their mean diameter with DLS. The amount of R848 loaded in M1 NV was determined by the reverse-phase ultrahigh-performance liquid chromatography (UHPLC) method according previous report [22] . The percentages of release of R848 were calculated according to a formula, release percentage (%) = Mr/Mt, where Mr is the amount of released R848, and Mt is the total amount of loaded R848.…”