Nanoplatform‐Based In Vivo Gene Delivery Systems for Cancer Therapy

Small, Journal Year: 2024, Volume and Issue: 20(30)

Published: March 5, 2024

Abstract Gene therapy uses modern molecular biology methods to repair disease‐causing genes. As a burgeoning therapeutic, it has been widely applied for cancer therapy. Since 1989, there have numerous clinical gene cases worldwide. However, few are successful. The main challenge of is the lack efficient and safe vectors. Although viral vectors show high transfection efficiency, their application still limited by immune rejection packaging capacity. Therefore, development non‐viral overwhelming. Nanoplatform‐based become hotspot in reasons mainly as follows. 1) Non‐viral can be engineered uptaken specific types cells or tissues, providing effective targeting capability. 2) protect goods that need delivered from degradation. 3) Nanoparticles transport large‐sized cargo such CRISPR/Cas9 plasmids nucleoprotein complexes. 4) highly biosafe, they not mutagenic themselves compared 5) easy scale preparation, which conducive conversion application. Here, an overview categories nanoplatform‐based vectors, limitations on development, applications

Language: Английский

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In vivo imaging of mitochondrial DNA mutations using an integrated nano Cas12a sensor

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Nov. 24, 2023

Mutations in mitochondrial DNA (mtDNA) play critical roles many human diseases. In vivo visualization of cells bearing mtDNA mutations is important for resolving the complexity these diseases, which remains challenging. Here we develop an integrated nano Cas12a sensor (InCasor) and show its utility efficient imaging live tumor-bearing mouse models. We co-deliver Cas12a/crRNA, fluorophore-quencher reporters Mg2+ into mitochondria. This process enables activation Cas12a's trans-cleavage by targeting mtDNA, efficiently cleave to generate fluorescent signals robustly sensing reporting single-nucleotide variations (SNVs) cells. Since engineered crRNA significantly increase sensitivity mismatches can identify tumor tissue metastases visualizing with mutant mtDNAs using InCasor. CRISPR nanoprobe holds potential applications mutation-related basic research, diagnostics gene therapies.

Language: Английский

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DNA Nanotechnology Targeting Mitochondria: From Subcellular Molecular Imaging to Tailor‐Made Therapeutics

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(36)

Published: June 14, 2024

Mitochondria, one of the most important organelles, represent a crucial subcellular target for fundamental research and biomedical applications. Despite significant advances in design DNA nanotechnologies variety bio-applications, dearth strategies that enable mitochondria targeting molecular imaging therapy remains an outstanding challenge this field. In Minireview, we summarize recent progresses on emerging application nanotechnology mitochondria-targeted tumor treatment. We first highlight engineering mitochondria-localized nanosensors situ detection diverse key molecules are essential to maintain mitochondrial functions, including microRNA, enzymes, small molecules, metal ions. Then, compile developments anti-tumor therapy, modularly designed nanodevices delivery therapeutic agents, programmed assembly interference. will place emphasis clarification chemical principles how nanobiotechnology can be various Finally, remaining challenges future directions field discussed, hoping inspire further development advanced toolkits both academic clinical regarding mitochondria.

Language: Английский

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Mitochondrial endogenous substance transport-inspired nanomaterials for mitochondria-targeted gene delivery

Advanced Drug Delivery Reviews, Journal Year: 2024, Volume and Issue: 211, P. 115355 - 115355

Published: June 5, 2024

Language: Английский

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Mitochondria-Targeted Photothermal-Chemodynamic Therapy Enhances Checkpoint Blockade Immunotherapy on Colon Cancer

Materials Today Bio, Journal Year: 2025, Volume and Issue: 31, P. 101542 - 101542

Published: Feb. 4, 2025

Immunotherapy has emerged as a hotspot for cancer treatment. However, the response rate of monotherapy remains relatively low in clinical settings. Photothermal therapy (PTT), which employs light energy to ablate tumors, can also activate tumor-specific immune responses. This effect been attributed several studies release damage-associated molecular patterns (DAMPs) triggered by mitochondrial injury. We propose that mitochondria-targeted PTT may better synergize with immunotherapy. Herein, we constructed multifunctional nanoplatform enables photothermal-chemodynamic combination conjugating indocyanine green-thiol (ICG-SH) and mercaptoethyl-triphenylphosphonium (TPP-SH) onto polyvinyl pyrrolidone (PVP)-coated gold-copper nanoparticles (AIT). Upon near-infrared (NIR) irradiation, AIT ablates cells amplifies chemodynamic (CDT), thereby inducing apoptosis tumor. The CDT promotes immunogenic cell death, could checkpoint blockade In bilateral mouse colon model, observed complete eradication light-irradiated primary tumors significant inhibition distant untreated group treated plus anti-PD-1 (αPD-1). found increase serum levels pro-inflammatory factors, including interleukin-6 (IL-6), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), following PTT/CDT/immunotherapy treatment, suggesting effective activation response. enhanced immunogenicity caused αPD-1 treatment resulted efficient antigen presentation, indicated increased infiltration dendritic (DCs) into tumor-draining lymph nodes (LNs). CD8+ T compared alone. Hence, mitochondria-targeting represents an strategy potentiate photothermal, chemodynamic, therapies metastatic cancer.

Language: Английский

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Organelle-oriented nanomedicines in tumor therapy: Targeting, escaping, or collaborating?

Bioactive Materials, Journal Year: 2025, Volume and Issue: 49, P. 291 - 339

Published: March 13, 2025

Language: Английский

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DNA Nanostructures for Rational Regulation of Cellular Organelles

JACS Au, Journal Year: 2025, Volume and Issue: unknown

Published: March 25, 2025

DNA nanotechnology has revolutionized materials science and biomedicine by enabling precise manipulation of matter at the nanoscale. nanostructures (DNs) in particular represent a promising frontier for targeted therapeutics. Engineered DNs offer unprecedented molecular programmability, biocompatibility, structural versatility, making them ideal candidates advanced drug delivery, organelle regulation, cellular function modulation. This Perspective explores emerging role modulating behavior through organelle-targeted interventions. We highlight current advances nuclear, mitochondrial, lysosomal targeting, showcasing applications ranging from gene delivery to cancer For instance, have enabled precision mitochondrial disruption cells, pH modulation enhance silencing, nuclear gene-editing templates. While hold immense promise advancing nanomedicine, outstanding challenges include optimizing biological interactions addressing safety concerns. highlights potential rational control organelles, which could lead novel therapeutic strategies advancement nanomedicines future.

Language: Английский

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DNA Nanotechnology Targeting Mitochondria: From Subcellular Molecular Imaging to Tailor‐Made Therapeutics

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(36)

Published: June 14, 2024

Abstract Mitochondria, one of the most important organelles, represent a crucial subcellular target for fundamental research and biomedical applications. Despite significant advances in design DNA nanotechnologies variety bio‐applications, dearth strategies that enable mitochondria targeting molecular imaging therapy remains an outstanding challenge this field. In Minireview, we summarize recent progresses on emerging application nanotechnology mitochondria‐targeted tumor treatment. We first highlight engineering mitochondria‐localized nanosensors situ detection diverse key molecules are essential to maintain mitochondrial functions, including microRNA, enzymes, small molecules, metal ions. Then, compile developments anti‐tumor therapy, modularly designed nanodevices delivery therapeutic agents, programmed assembly interference. will place emphasis clarification chemical principles how nanobiotechnology can be various Finally, remaining challenges future directions field discussed, hoping inspire further development advanced toolkits both academic clinical regarding mitochondria.

Language: Английский

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Tyrosinase‐Woven Melanin Nets for Melanoma Therapy through Targeted Mitochondrial Tethering and Enhanced Photothermal Treatment

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(44)

Published: Sept. 17, 2024

Abstract Manipulating intracellular biological processes and organelles has emerged as a pivotal strategy to influence cellular physiological functions. Mitochondria, recognized the powerhouse of cells, play crucial role in tumorigenesis progression. Inspired by Nature's tyrosinase‐catalyzed melanin formation within melanoma here an approach is developed using polysaccharide dually‐functionalized with tyrosine triphenylphosphine (TPP) for targeted mitochondria cross‐linking cells. This technique intricately weaves nets serving tether effectively decelerating tumor metabolism through nanoparticle‐net transformation. Tyrosinase acts “needle”, while functionalized serves “string” successfully constructing cell. Furthermore, not only facilitates production artificial but also enhances photothermal conversion efficiency leading decrease growth. study unveils non‐drug method regulating organelle activity introduces treatment. work sheds light on manipulation functions holds promise advancing cancer therapeutic strategies.

Language: Английский

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Modified Oxygen Metabolism Toward “Sunlight‐Friendly” Photodynamic Therapy

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 4, 2024

Abstract Phototoxicity poses a substantial challenge in photodynamic therapy, resulting intolerable skin damage, visual impairment, and reduced quality of life. Current coping strategies, primarily focus on avoiding inappropriate photoactivation developing targeted photosensitizers, have not effectively addressed this problem. Hence, study aims to develop “sunlight‐friendly” therapy strategy. Here, 1‐methoxyphenazine methosulfate (MPMS) is innovatively identified as key substance achieving modified oxygen metabolism. MPMS demonstrates efficient catalytic shuttling under abnormal intracellular H 2 O levels, introducing novel protective approach for metabolism numerous life processes. By controlling administration, the switch photosensitizer states between “ON” (killing tumor cells) “OFF” (safeguarding normal can be achieved. This mitigated phototoxicity holds potential widespread clinical application.

Language: Английский

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