Nanoengineering a Zeolitic Imidazolate Framework‐8 Capable of Manipulating Energy Metabolism against Cancer Chemo‐Phototherapy Resistance

Abstract

Chemo‐phototherapy has emerged as a promising approach to complement traditional cancer treatment and enhance therapeutic effects. However, it still faces the challenges of drug efflux transporter‐mediated chemoresistance and heat shock proteins (HSPs)‐mediated phototherapy tolerance, which both depend on an excessive supply of adenosine triphosphate. Therefore, manipulating energy metabolism to impair the expression or function of P‐glycoprotein (P‐gp) and HSPs may be a prospective strategy to reverse cancer therapeutic resistance. Herein, a chondroitin sulfate (CS)‐functionalized zeolitic imidazolate framework‐8 (ZIF‐8) chemo‐phototherapy nanoplatform (CS/ZIF‐8@A780/DOX NPs) is rationally designed that is capable of manipulating energy metabolism against cancer therapeutic resistance by integrating the photosensitizer IR780 iodide (IR780)‐conjugated atovaquone (ATO) (A780) and the chemotherapeutic agent doxorubicin (DOX). Mechanistically, ATO and zinc ions that are released in the acidic tumor microenvironment can lead to systematic energy exhaustion through disturbing mitochondrial electron transport and the glycolysis process, thus suppressing the activity of P‐gp and HSP70, respectively. In addition, CS is used on the surface of ZIF‐8@A780/DOX NPs to improve the targeting capability to tumor tissues. These data provide an efficient strategy for manipulating energy metabolism for cancer treatment, especially for overcoming cancer chemo‐phototherapy resistance.

Developing Single-Atomic Manganese Nanozymes for Synergistic Mild Photothermal/Multienzymatic Therapy

“…The increased cellular ROS level can typically destroy the mitochondrial membrane and induce mitochondrial dysfunction, thereby causing a significant decrease in adenosine triphosphate (ATP) production and severe cell damage. ,,, We investigated Mn-SAN-mediated mitochondrial dysfunction using a 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethyl-imidacarbocyanine iodide (JC-1) probe to indicate the loss of mitochondrial membrane potential (MMP) (Figure a). Compared to the PBS-only, NIR-II-only, or UCNs + NIR-II group, the increased disruption of the mitochondrial membrane was found in Saos-2 cells after treating with Mn-SANs, which decreased the red fluorescence and led to obvious green fluorescence.…”

Carrier-Free Nanoplatform via Evoking Pyroptosis and Immune Response against Breast Cancer

“…Tumor recurrence is one of the most fatal problems for patients with cancer. , Therefore, we adopted a tumor recurrence model to investigate the durable immune memory effect of A-C/NPs (Figure A). 4T1-Luc tumor-bearing mouse model was established and treated with PBS, Ara-C, Ce6 + Laser, or A-C/NPs + Laser, respectively.…”

Nanomedicine-based modulation of redox status for cancer therapy

“…[62] Metallic NPs have improved potential to take advantage of the oxidative radicals generated by the metals for selective destruction of diseased cells, thus emerging as valuable and efficient diagnostic and anticancer agents. [63] Generally, metallic elements function as charged vehicles and generate soluble cations to form complexes with natural cellular components. [64] Additionally, metal ions with a positive charge may regulate electron transport to help catalyze substrates and enzymes.…”