Acid-Unlocked Two-Layer Ca-Loaded Nanoplatform to Interfere With Mitochondria for Synergistic Tumor Therapy

International Journal of Nanomedicine, Год журнала: 2025, Номер Volume 20, С. 1899 - 1920

Опубликована: Фев. 1, 2025

Background: The development of selective formulations able to target and kill tumor cells without the application external energy has shown great promise for anti-tumor therapy. Methods: Here, we report a "nanobomb" that explosively increases Ca content within cells. It can selectively release 2+ generate H 2 O in microenvironment (TME) by acid-triggered degradation two-layer protective shell (ie, unlocking "double-lock"). This material, termed CaO @ZIF8:CUR@PAA, comprises core coated with ZIF-8 framework, which was then loaded curcumin (CUR) again polyacrylic acid (PAA). Results: Under slightly acidic conditions TME, PAA (first lock) breaks down first exposing @ZIF8 CUR inside cell. Then, ZIF8 (second is degraded response deposit , . promote from endoplasmic reticulum cytoplasm, inhibit outflow accumulates large amount intracellularly together exogenous (calcium storms). powerful calcium storm causes mitochondrial dysfunction. presence further oxidative damage cell membranes mitochondria where intracellular ROS production far exceeds clearance. @ZIF8:CUR@PAA NPs induce S cycle arrest apoptosis multiplication growth. Oxidative damage-triggered immunogenic death (ICD) turn leads polarization macrophages M1 phenotype, inducing inhibiting proliferation metastasis. Discussion: two-step nanoplatform therapeutic modality combines damage. mode triggers leading ICD material induces blockade during treatment proliferation. Robust vitro vivo data demonstrate efficacy this approach as an anticancer platform, paving way nanomaterials immune-triggered cancer Highlights: - A new accumulation plays role activate antitumor immunity.- Double-locked structure slows premature decomposition .- platform allows accumulate cells.- dysfunction, apoptosis, macrophage polarization.- Potent effects are seen both vivo. Keywords: Calcium ion load, controlled-release nanomaterials, shell, pH responsive drug release, reactive oxygen species, anti-cancer

Язык: Английский

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Advances and prospects of RNA delivery nanoplatforms for cancer therapy

Acta Pharmaceutica Sinica B, Год журнала: 2024, Номер 15(1), С. 52 - 96

Опубликована: Сен. 14, 2024

Modern oncology is rapidly evolving, driven by recent advances in RNA-based therapeutics. As new emerging cutting-edge technology, mRNA vaccines hold excellent promise for encoding immunostimulatory molecules, tumor-associated antigens, neoantigens, and chimeric antigen receptors T-cell reprogramming. RNA interference tools enable highly effective post-transcriptional gene silencing that has progressed towards more tailored antitumor treatments targeting key molecular players tumor progression drug resistance. The inherent challenges limitations of tools, such as size, low stability surface charges hindering direct cell entry, along with the short circulatory half-life rapid clearance, call improved delivery systems enabling enhanced delivery. Nanoplatforms, particularly certain types lipid, polymeric nanoparticles inorganic nanoparticles, provide designed means to address cellular uptake. This paper explores barriers while giving insight into future perspective cancer therapeutics context nanoplatforms during development.

Язык: Английский

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Nanocarrier-mediated modulation of cGAS-STING signaling pathway to disrupt tumor microenvironment

Naunyn-Schmiedeberg s Archives of Pharmacology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 5, 2025

Язык: Английский

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Nano-Delivery of STING Agonists: Unraveling the Potential of Immunotherapy

Acta Biomaterialia, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

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