Oncolytic Impediment/Promotion Balance Disruption by Sonosensitizer-Free Nanoplatforms Unfreezes Autophagy-Induced Resistance to Sonocatalytic Therapy

Abstract

Autophagy as a double-edged sword features an oncolytic impediment/promotion balance, which manipulates tumor progression. From this perspective, a sonosensitizer-free targeting oncolytic nanoplatform (SFTON) consisting of chloroquine (CQ) and porphyrin-structured metal centers (PMCS) was engineered to break this balance for enhancing antitumor activity. Porphyrin structure retention in a ZIF-8-derived hydrophobic carbon skeleton retained high stability and high sonocatalytic activity, and the hydrophobic carbon skeleton capable of adsorbing air provided cavitation nuclei for further elevating sonocatalytic activity. More significantly, the encapsulated CQ as the autophagy inhibitor reprogrammed autophagy, terminated the autophagy-induced self-protection or self-detoxification, and unfroze the resistances to reactive oxygen species (ROS) therapy associated with ROS accumulation and ROS activity. Systematic experiments reveal the action principles and validate that the induced apoptosis and blockaded autophagosome escalation into the autolysosome were two activated pathways to magnify the antitumor sonocatalytic therapy. Contributed by these actions, the SFTON-unlocked oncolytic impediment/promotion balance disruption strategy acquired considerable antitumor outcomes in vivo and in vitro against liver tumor progression, especially after combining with AS1411-mediated active targeting. This impediment/promotion balance disruption enabled by the SFTON can serve as a general method to elevate ROS-based antitumor activity.

Truncated PD1 Engineered Gas‐Producing Extracellular Vesicles for Ultrasound Imaging and Subsequent Degradation of PDL1 in Tumor Cells

“…To this end, tumor tumor-targeting nanoscale ultrasound contrast agent called tnUCA was designed and played an indispensable role in ultrasound theranostic. [17] It should be noted that the nanoscale NPs cannot effectively respond to the US because of their poor echogenic sensitivity, resulting in a significant decrease in image contrast compared with MBs. [3a] Mechanistically, the sub-micrometer PFC droplets exhibited weak US-scattering performance because of their low impedance and compressibility, behaving as linear Rayleigh scatterers.…”

Breakthroughs in nanozyme-inspired application diversity

“…(4) To elevate the treatment efficiency, combined or synergistic therapy is usually encouraged. [139][140][141][142][143][144][145][146][147][148][149][150][151][152][153][154][155][156][157][158] Inspired by this, nanozymes can be integrated with immunotherapy, chemotherapy, and other ROS-highlighted therapy to magnify the treatment efficiency. This direction will also arouse more interests, propelling clinical translation especially when imparting these functions into one platform and realizing the all-in-one strategy.…”

Dual‐Functional Artificial Peroxidases with Ferriporphyrin Centers for Amplifying Tumor Immunotherapies via Immunogenic Cell Death

“…[38,39] Most currently established sonosensitizers are based on small molecules, for instance, porphyrin (Por), phthalocyanine (Pc), and its metal complex. [40][41][42][43][44] However, two major challenges still inhibit their tumor immunotherapies: 1) the insufficient US-energy conversion efficiency, instability, and self-quenching of these small molecules under physiological conditions, and 2) the poor TME sensitivity during ROS production. [45][46][47] Therefore, it is urgently necessary to engineer efficient sonosensitizers that integrate both TME-adaptive and US-controllable ROS production capabilities to amplify tumor immunotherapies.…”