NIR-II Responsive Molybdenum Dioxide Nanosystem Manipulating Cellular Immunogenicity for Enhanced Tumor Photoimmunotherapy

Abstract

Photothermal therapy (PTT) in the second nearinfrared (NIR-II) window has emerged as a better candidate for deep-tissue tumor elimination. More interestingly, the photothermal ablated tumor cells also manifest somewhat immunostimulation potency to elicit antitumor immunity, although most dying cells are undergoing apoptosis that is commonly considered as immunologically silent. Here, a NIR-II responsive nanosystem is established for tumor photoimmunotherapy using molybdenum dioxide (MoO 2 ) nanodumbbells as the nanoconverter. Meanwhile, an apoptosis-blocking strategy is proposed to regulate the cell death pattern under NIR-II laser irradiation in order to improve the immunogenic cell death. The nanoformulation can efficiently block caspase 8-dependent apoptotic pathway in photothermal ablated tumor cells and transform into more immunogenic death patterns, thereby activating systemic immunity to inhibit tumor growth and metastasis. In addition, this strategy also helps enhance the body's responses to α-PD-1 immune checkpoint inhibitor, which implies a potential optimal combination for cancer immunotherapy.

Interrelation between Programmed Cell Death and Immunogenic Cell Death: Take Antitumor Nanodrug as an Example

“…[79][80][81][82] Moreover, PTT can increase the temperature at the tumor site to induce ERS. [83] CT can lead to ROS production or chemical toxicity, etc. [84] Other regulation modes such as calcium ions overload and gas therapy can also induce ICD.…”

“…Mechanisms Designs PDT Photosensitizers produce ROS under light irradiation Relieve tumor hypoxia [87,88] Increase tumor uptake [79] Combine immunotherapy [89,90] SDT Sonosensitizer produce ROS under ultrasonic irradiation Increase the degree of inertial cavitation [80] Increased targeting [91][92][93][94] Disrupting the redox balance in the cell [95] CDT Fenton reaction produce ROS Metal based nanomaterials [81] CT Anthracyclines induce CRT exposure and ROS production: DOX, Oxp, mitoxantrone, and so on Responsive nanoplatforms as drug carriers [82,84,[96][97][98][99] PTT Photothermal effect Photothermal nanomaterials [83,[100][101][102] Other regulation modes Gas therapy: hydrogen (H 2 ), nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H 2 S), sulfur dioxide (SO 2 ), and so on induce ERS Gas nanogenerator [103][104][105][106][107] Calcium ion regulation Calcium ions overload [85] cells including myeloid-derived suppressor cells (MDSCs) and regulatory cells (Tregs), whereas it increased cytotoxic T lymphocytes to enhance ICD.…”

Nanomaterials for photothermal cancer therapy

“…8A ). 130 Compared with the NIR I region, NIR II PTT has stronger tissue penetration ability, enabling better photothermal ablation of deep tumors. 131 Interestingly, researchers found that MoO 2 -mediated PTT also induced an immune response in the body, increasing the immune stimulation of tumor tissue and releasing a large number of damage-associated molecular patterns (DAMPs) through the process of immunogenic cell death (ICD) in the tumor tissue.…”

Multifunctional Nano‐Biomaterials for Cancer Therapy via Inducing Enhanced Immunogenic Cell Death

“…constructed NIR‐II responsive nano system using molybdenum dioxide (MoO 2 ) nano dumbbells as the nanoconverter. [ 63 ] An apoptosis‐blocking strategy is proposed by blocking the caspase 8‐dependent apoptotic pathway to improve the ICD. A metal‐coordinated micelle was designed by the self‐assembly of manganese (Mn), a stimulator of interferon genes (STING) agonist (ABZI) and naphthalocyanine (ONc, a photosensitizer) coordinated nanoparticles in maleimide‐modified Pluronic F127 (malF127) micelles to enhance antigen presentation and antitumor immunity.…”