A Supramolecular, Triple Negative Breast Cancer‐Targeting Avidin‐Photosensitizer DOI Creative Commons

Bingjie Gao,

Christoph Schäfers, Seah Ling Kuan

et al.

Macromolecular Bioscience, Journal Year: 2025, Volume and Issue: unknown

Published: March 25, 2025

The potential of photodynamic therapy (PDT) in combination with chemotherapy to improve treatment outcomes for triple-negative breast cancer (TNBC), which no targeted is available, the subject considerable investigation. In PDT, photosensitizers (PSs) are frequently administered directly but do not selectively target cells. To address delivery a PS TNBC and enhance cellular uptake, Ru-NH2-modified avidin bioconjugate (RuAvi) via Tyr-specific modification using Mannich reaction prepared. RuAvi further assembled cinnamoyl peptide-F(D)LF(D)LFK-NH2 (FK), binds formyl peptide receptor 1, overexpressed TNBC. Notably, modified Avi still possesses ability efficiently bind biotin assembly up four copies FK peptides. resultant FK4-RuAvi exhibited an IC50 value 0.36 ± 0.08 µM, ≈3.5-fold lower than that (1.25 0.09 µM), upon irradiation MDA-MB-231 also shows efficient uptake tumor spheroids significant toxicity after compared control RuAvi. presented strategy has efficacy PDT meet high demand therapies treat TNBC, such as adjuvant surgery.

Language: Английский

A NIR‐II‐Emissive Organic Nanomedicine with Biomimetic Engineering for High‐Contrast Targeted Bioimaging and Multiple Phototherapies of Pancreatic Tumors DOI
Yiwei Wang, Jie Zhang, Yu Wang

et al.

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

Published: July 2, 2024

Abstract Recent advances are achieved in the design and development of efficient organic photosensitizers (PSs), especially with fluorescence imaging navigation second near‐infrared (NIR‐II, 1000–1700 nm) region. However, there simply a handful NIR‐II emissive PSs oxygen‐independent capability due to scarcity high‐performance NIR‐responsive materials targeted delivery. Herein, NIR‐II‐emissive nanomedicine biomimetic engineering for multiple phototherapies pancreatic tumors is reported. An A‐D‐A‐type conjugated small‐molecule TPC designed used prepare water‐dispersive nanoparticles, which demonstrated high efficiency type I II photodynamic performances, good photothermal conversion 57%, bright emission quantum yield 9.8% under 808 nm light irradiation. With cancer cell membrane camouflage, high‐resolution bioimaging whole‐body blood vessels tumors. Antitumor experiments tumor elimination biosafety This work versatile enhanced tumor‐targeting superior phototheranostics, providing feasible idea evolution theranostics.

Language: Английский

Citations

7
Ru(II) Complexes with Absorption in the Photodynamic Therapy Window: 1O2 Sensitization, DNA Binding, and Plasmid DNA Photocleavage DOI

Sean J. Steinke,

Marilyn N. Dunbar,

M. Agustina Amalfi Suarez

et al.

Inorganic Chemistry, Journal Year: 2024, Volume and Issue: 63(24), P. 11450 - 11458

Published: June 1, 2024

Two Ru(II) complexes, [Ru(pydppn)(bim)(py)]2+ [2; pydppn = 3-(pyrid-2′-yl)-4,5,9,16-tetraaza-dibenzo[a,c]naphthacene; bim 2,2′-bisimidazole; py pyridine] and [Ru(pydppn)(Me4bim)(py)]2+ [3; Me4bim 2,2′-bis(4,5-dimethylimidazole)], were synthesized characterized, their photophysical properties, DNA binding, photocleavage evaluated compared to [Ru(pydppn)(bpy)(py)]2+ (1; bpy 2,2′-bipyridine). Complexes 2 3 exhibit broad 1MLCT (metal-to-ligand charge transfer) transitions with maxima at ∼470 nm shoulders ∼525 ∼600 that extend ∼800 nm. These bands are red-shifted relative those of 1, attributed the π-donating ability ligands. A strong signal 550 is observed in transient absorption spectra 1–3, previously assigned as arising from a pydppn-centered 3ππ* state, lifetimes ∼19 μs for 1 ∼270 ns 3. number methods used characterize mode binding 1–3 DNA, including titrations, thermal denaturation, viscosity changes, circular dichroism, all which point intercalation pydpppn ligand between nucleobases. The plasmid pUC19 was upon irradiation visible red light, sensitized generation 1O2 by complexes. findings indicate ligand, together pydppn, serves shift complexes photodynamic therapy window, 600–900 nm, also excited state efficient production cytotoxic singlet oxygen.

Language: Английский

Citations

6
Photoresponsive Drug Delivery Systems: Challenges and Progress DOI Creative Commons
Yang Yang, Kaiqi Long,

Yuxiu Chu

et al.

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(38)

Published: June 12, 2024

Abstract Photoresponsive drug delivery systems (PDDSs) have emerged as a promising toolbox for delivery, offering precise control over the site, duration, and dosage of light‐triggered medication. It allows controlled release, photo‐triggered targeting, diagnosis, treatment, improving precision efficacy therapies various diseases. Despite progress in designing different PDDSs, clinical translation has been limited due to obstacles. Herein, this review article focuses on three critical challenges PDDSs: 1) accumulation at diseased lesions, 2) light irradiation, 3) penetration tissues. Also, summarizes discusses current advancements strategies address these challenges. Overall, it emphasizes need clarify from bench bedside develop enhance therapeutic outcomes, increase compatibility patient compliance, unlock possibilities therapies.

Language: Английский

Citations

6
Leveraging the Photofunctions of Transition Metal Complexes for the Design of Innovative Phototherapeutics DOI Creative Commons
Lawrence Cho‐Cheung Lee, Kenneth Kam‐Wing Lo

Small Methods, Journal Year: 2024, Volume and Issue: 8(11)

Published: Sept. 25, 2024

Abstract Despite the advent of various medical interventions for cancer treatment, disease continues to pose a formidable global health challenge, necessitating development new therapeutic approaches more effective treatment outcomes. Photodynamic therapy (PDT), which utilizes light activate photosensitizer produce cytotoxic reactive oxygen species (ROS) eradicating cells, has emerged as promising approach due its high spatiotemporal precision and minimal invasiveness. However, widespread clinical use PDT faces several challenges, including inefficient production ROS in hypoxic tumor microenvironment, limited penetration depth biological tissues, inadequate accumulation photosensitizers at site. Over past decade, there been increasing interest utilization photofunctional transition metal complexes applications their intriguing photophysical photochemical properties. This review provides an overview current design strategies used innovative phototherapeutics, aiming address limitations associated with achieve The challenges future perspectives on translation are also discussed.

Language: Английский

Citations

6
A Bioactive Photosensitizer for Hypoxia‐Tolerant Molecular Targeting‐Photo‐Immunotherapy of Malignant Tumor DOI

Lianfeng Fan,

Chuanjiang Jian,

Ling Li

et al.

Advanced Functional Materials, Journal Year: 2023, Volume and Issue: 34(12)

Published: Dec. 15, 2023

Abstract Photosensitizers (PSs) with effective reactive oxygen species generation ability against hypoxia are of great potential for clinical treatment malignant tumors. However, complex tumor microenvironment, such as antioxidative responses and immunosuppression, would ineluctably limit the efficiency photodynamic therapy (PDT). Herein, a molecular‐targeting photosensitizer QTANHOH is rationally designed histone deacetylases (HDACs‐targeting photo‐immunotherapy application. The PS displays excellent type‐I/II PDT performance, exhibiting significant phototoxicity toward cancer cells half maximal inhibitory concentration (IC 50 ) less than 10 n m in both normoxia conditions under blue laser irradiation. Moreover, bioactive compound could inhibit HDACs activate immune microenvironment to boost efficacy on immunocompetent BALB/c mice breast cancer, leading eradication solid inhibition metastasis. Notably, introduces an alternative strategy achieve superior phototherapy therapy.

Language: Английский

Citations

15
Synergization of an endoplasmic reticulum-targeted iridium(III) photosensitizer with PD-L1 inhibitor for oral squamous cell carcinoma immunotherapy DOI Creative Commons
Jiaying Zhou,

Qing-Hua Shen,

Xiao-Jing Hong

et al.

Chemical Engineering Journal, Journal Year: 2023, Volume and Issue: 474, P. 145516 - 145516

Published: Aug. 17, 2023

Inefficient activation of tumor immunogenicity and sustained immunosuppressive microenvironments severely impede the clinical application photodynamic therapy (PDT) in oral squamous cell carcinoma (OSCC). Herein, two type I/II iridium(III) photosensitizers (Ir1 Ir2) targeting endoplasmic reticulum (ER) are designed as immunogenic death (ICD) inducers. Ir1-meidated PDT treatment adaptively upregulates programmed death-ligand 1 (PD-L1) expression vitro. Moreover, Ir1-mediated stimulates dendritic maturation, T lymphocyte infiltration antitumor cytokine secretion, synergizes with PD-L1 inhibitor to transform immune-suppressive "cold tumor" immune-responsive "hot vivo. Our study firstly paves way for combination metal-based photosensitizing ICD inducer enhanced immunotherapy.

Language: Английский

Citations

14
Ruthenium-Cathepsin Inhibitor Conjugates for Green Light-Activated Photodynamic Therapy and Photochemotherapy DOI
Madeline Denison, Santana P. Garcia, Alexander Ullrich

et al.

Inorganic Chemistry, Journal Year: 2024, Volume and Issue: 63(17), P. 7973 - 7983

Published: April 15, 2024

Dysregulated cathepsin activity is linked to various human diseases including metabolic disorders, autoimmune conditions, and cancer. Given the overexpression of in tumor microenvironment, inhibitors are promising pharmacological agents drug delivery vehicles for cancer treatment. In this study, we describe synthesis photochemical biological assessment a dual-action agent based on ruthenium that conjugated with inhibitor, designed both photodynamic therapy (PDT) photochemotherapy (PCT). The ruthenium-cathepsin inhibitor conjugate was synthesized through an oxime click reaction, combining pan-cathepsin E64d Ru(II) PCT/PDT fragment [Ru(dqpy)(dppn)], where dqpy = 2,6-di(quinoline-2-yl)pyridine dppn benzo[i]dipyrido[3,2-a:2',3'-c]phenazine. Photochemical investigations validated conjugate's ability release triazole-containing PCT generate singlet oxygen PDT upon exposure green light. Inhibition studies demonstrated potent irreversible inactivation purified intracellular cysteine cathepsins. Two [Ru(dqpy)(dppn)] moiety were evaluated photoinduced cytotoxicity 4T1 murine triple-negative breast cells, L929 fibroblasts, M0, M1, M2 macrophages. displayed notable selectivity inducing cell death under irradiation compared dark mitigating toxicity observed triazole control complex [Ru(dqpy)(dppn)(MeTz)]

Language: Английский

Citations

5
Designing macrophage membrane-engineered ruthenium/selenium nanoparticles to block bone metastasis of breast cancer DOI

Meijin Yang,

Zhiying Tang,

M Kellis

et al.

Nano Research, Journal Year: 2024, Volume and Issue: 17(8), P. 7504 - 7512

Published: June 14, 2024

Language: Английский

Citations

5
Revolutionizing anticancer treatment: Ruthenium-based nanoplatforms pave new paths DOI
Dipanjan Karati,

Shreyasi Meur,

Swarupananda Mukherjee

et al.

Coordination Chemistry Reviews, Journal Year: 2024, Volume and Issue: 519, P. 216118 - 216118

Published: July 30, 2024

Language: Английский

Citations

5
Immunogenic Cell Death Induction and Oxygenation by Multifunctional Hollow Silica/Copper-Doped Carbon Dots DOI

Mingyang Liu,

Hui Zhang,

Yujun Bao

et al.

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: 16(15), P. 18534 - 18550

Published: April 4, 2024

The metastasis and recurrence of cancer are related to immunosuppression hypoxia in the tumor microenvironment. Activating immune activity improving hypoxic environment face essential challenges. This paper reports on a multifunctional nanomaterial, HSCCMBC, that induces immunogenic cell death through powerful photodynamic therapy/chemodynamic therapy synergistic antitumor effects. microenvironment changed from immunosuppressive type type, activated system, decomposed hydrogen peroxide generate oxygen based Fenton-like reaction, effectively increased level intracellular O2 with assistance 3-bromopyruvate, respiratory inhibitor. structure composition HSCCMBC were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, diffraction, infrared etc. Oxygen probe RDPP was used investigate inside outside cell, hydroxyl radical tetramethylbenzidine reaction ability. immunofluorescence method investigated expression various markers hypoxia-inducing factors vitro vivo after treatment. In experiments indicate is an excellent agent expected be candidate drug for immunotherapy.

Language: Английский

Citations

4