Cancer immune therapy using engineered ‛tail-flipping’ nanoliposomes targeting alternatively activated macrophages

Abstract

Alternatively-activated, M2-like tumor-associated macrophages (TAM) strongly contribute to tumor growth, invasiveness and metastasis. Technologies to disable the pro-tumorigenic function of these TAMs are of high interest to immunotherapy research. Here we show that by designing engineered nanoliposomes bio-mimicking peroxidated phospholipids that are recognised and internalised by scavenger receptors, TAMs can be targeted. Incorporation of phospholipids possessing a terminal carboxylate group at the sn-2 position into nanoliposome bilayers drives their uptake by M2 macrophages with high specificity. Molecular dynamics simulation of the lipid bilayer predicts flipping of the sn-2 tail towards the aqueous phase, while molecular docking data indicates interaction of the tail with Scavenger Receptor Class B type 1 (SR-B1). In vivo, the engineered nanoliposomes are distributed specifically to M2-like macrophages and, upon delivery of the STAT6 inhibitor (AS1517499), zoledronic acid or muramyl tripeptide, these cells promote reduction of the premetastatic niche and/or tumor growth. Altogether, we demonstrate the efficiency and versatility of our engineered “tail-flipping” nanoliposomes in a pre-clinical model, which paves the way to their development as cancer immunotherapeutics in humans.

Microwave-Responsive Edge-Oxidized Graphene for Imaging-Guided Neoadjuvant Thermal Immunotherapy via Promoting Immunogenic Cell Death and Redressing Hypoxia

“…Current nanotherapy increasingly focuses on targeting or reprogramming the tumor microenvironment. 55−58 However, existing studies often concentrate on specific cellular components like TAMs, 59 or physiological characteristics such as pH and hypoxia, 60,61 not aligning with the complexity, diversity, and variability of the tumor microenvironment. Our results demonstrate that EOG contributes to alleviating tumor hypoxia and enhances ICD when combined with microwaves.…”

“…30,64 Additionally, TAMs undergo polarization into the M1 phenotype, and the cytokine secretion profile shifts toward an antitumor response, ultimately resulting in the reprogramming of tumor microenvironments. 59,65 Interestingly, microwave-based thermal immunotherapy also leads to the upregulation of humoral immunityrelated immune cells and cytokines, indicating the involvement of humoral immunity. However, the role of humoral immunity in thermal immunotherapy is still unknown and deserves further investigation and attention.…”

“…Compared to normal tissues, the tumor microenvironment undergoes significant changes, such as hypoxia, immune infiltration, and acidic pH. − Especially in untreated tumors, this harsh microenvironment limits the effectiveness of neoadjuvant immunotherapy. Current nanotherapy increasingly focuses on targeting or reprogramming the tumor microenvironment. − However, existing studies often concentrate on specific cellular components like TAMs, or physiological characteristics such as pH and hypoxia, , not aligning with the complexity, diversity, and variability of the tumor microenvironment. Our results demonstrate that EOG contributes to alleviating tumor hypoxia and enhances ICD when combined with microwaves.…”

Prognostic roles of a novel basement membranes-related gene signature in lung adenocarcinoma

“…Tumor infiltrating lymphocytes (TIL) were indispensable for the occurrence and development of tumors ( Kuninty et al, 2022 ). Although the monotherapy of PD-1 or PD-L1 was generally well tolerated and the efficacy is limited, combination therapy increased the risk of immune-related adverse events.…”

Black Phosphorus Nanosheets Grafted with Gold Nanorods and Carbon Nanodots for Synergistic Antitumor Therapy

“…To increase the number of cancer survivors, novel strategies for early cancer diagnosis and treatment are highly desired. The goal of cancer therapy is focused on the effective killing of cancer cells, while normal cells are not harmed. , Despite rapid progress in the understanding of conventional surgical procedures, chemotherapy, radiotherapy, and immunotherapy, great challenges still exist including severe toxic effects, high cost, drug resistance, and low response rates. − Phototherapy is also a powerful treatment pattern, which has attracted tremendous interest with the advantages like noninvasive treatments and limited side effects and drug resistance . Photodynamic therapy (PDT) and photothermal therapy (PTT) are two main strategies applied for phototherapy of cancer. , PDT mainly utilizes reactive oxygen species (ROS) generated from photosensitizers for the destruction of cancer cells and the disruption of microvascular, which has already been sanctioned by the Food and Drug Administration of America (FDA). , ROS molecules ( e.g.…”