Independent of tumor type and non‐invasive or minimally‐invasive feature, current physical treatments including ultrasound therapy, microwave ablation (MWA), and radiofrequency ablation (RFA) are widely used as the local treatment methods in clinics for directly killing tumors and activating systematic immune responses. However, the activated immune responses are inadequate and incompetent for tumor recession, and the incomplete thermal ablation even aggravates the immunosuppressive tumor microenvironment (ITM), resulting in the intractable tumor recurrence and metastasis. Intriguingly, nanomedicine provides a powerful platform as they can elevate energy utilization efficiency and augment oncolytic effects for mitigating ITM and potentiating the systematic immune responses. Especially after combining with clinical immunotherapy, the anti‐tumor killing effect by activating or enhancing the human anti‐tumor immune system is reached, enabling the effective prevention against tumor recurrence and metastasis. This review systematically introduces the cutting‐edge progress and direction of nanobiotechnologies and their corresponding nanomaterials. Moreover, the enhanced physical treatment efficiency against tumor progression, relapse, and metastasis via activating or potentiating the autologous immunity or combining with exogenous immunotherapeutic agents is exemplified, and their rationales are analyzed. This review offers general guidance or directions to enhance clinical physical treatment from the perspectives of immunity activation or magnification.
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.
Objective. The off-target effects and severe side effects of PPARα and LXRα agonists greatly limit their application in atherosclerosis (AS). Therefore, this study intended to use mesoporous silica nanoparticles as carriers to generate MnO nanoparticles in situ with T1WI-MRI in mesoporous pores and simultaneously load PPARα and LXRα agonists. Afterward, cRGD-chelated platelet membranes can be used for coating to construct a new nanotheranostic agent. Methods. cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles were synthesized by a chemical method. Dynamic light scattering (DLS) was utilized to detect the size distribution and polydispersity index (PDI) of the nanoparticles. The safety of the nanoparticles was detected by CCK8 in vitro and HE staining and kidney function in vivo. Cell apoptosis was detected by flow cytometry detection and TUNEL staining. Oxidative stress responses (ROS, SOD, MDA, and NOX levels) were tested via a DCFH-DA assay and commercial kits. Immunofluorescence and phagocytosis experiments were used to detect the targeting of nanoparticles. Magnetic resonance imaging (MRI) was used to detect the imaging performance of cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles. Using western blotting, the expression changes in LXRα and ABCA1 were identified. Results. cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles were successfully established, with a particle size of approximately 150 nm and PDI less than 0.3, and showed high safety both in vitro and in vivo. cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles showed good targeting properties and better MRI imaging performance in AS. cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles showed better antioxidative capacities, MRI imaging performance, and diagnostic and therapeutic effects on AS by regulating the expression of LXRα and ABCA1. Conclusion. In the present study, cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles with high safety and the capacity to target vulnerable plaques of AS were successfully established. They showed better performance on MRI images and treatment effects on AS by promoting cholesterol efflux through the regulation of ABCA1. These findings might address the problems of off-target effects and side effects of nanoparticle-mediated drug delivery, which will enhance the efficiency of AS treatment and provide new ideas for the clinical treatment of AS.
Aim: To design a new treatment based AKT inhibitor (MLF), as a therapeutic target, and doxorubicin, as a chemotherapy agent, co-loaded on Modern metal organic frameworks (MFOs) by using ZIF-8 nanomaterials. Methods: We synthesized a MOFs (ZIF-8) as a drug carrier, and
achieved simultaneous loading of the chemotherapeutic drug DOX and AKT inhibitor MFL (ZIF-8/DOX/MFL), as a drug carrier. In addition, we used MTT assay, evaluation the expression of collagen-1, and tumor drug uptake to evaluate the efficacy of our treatment. We further used ultrasound to modify
the red blood cell membrane on the surface of ZIF-8/DOX/MLF to improve the biological safety and stability of the drug-carrying system, and finally obtained ZIF-8/DOX/MLF/RBCM. Results: Our results showed that the tumor enrichment in the ZIF-8/MLF/RBCM group was about 3 times that of
the ZIF-8/RBCM group; and both in vivo and in vitro imaging of mouse organs showed that MLF has the function of assisting drug delivery and enhancing drug tumor enrichment, according to fluorescence quantification. Conclusion: The research results show that the ZIF-8/DOX/MLF/RBCM
can achieve the purpose of sensitizing new tumor chemotherapy in breast cancer.
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