X-ray induced photodynamic therapy (PDT) with a mitochondria-targeted liposome delivery system

Gu, Xue-Fan; Shen, Chao; Li, Hua; Goldys, Ewa M.; Deng, Wei

doi:10.1186/s12951-020-00644-z

Cited by 39 publications

(33 citation statements)

References 44 publications

(49 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It can be speculated that the conjugation of cationic TPP may induce the “ponton sponge effect” in the acidic lysosomal matrix to cause destructive osmotic swelling, which may account for the probable escape of MLipRIR NPs from endocytosis by lysosomes and their subsequent enrichment in mitochondria. Such a lysosomal escape mechanism has also been validated in previous well-established TPP-modified liposomal systems 52 , 53 .…”

Section: Resultsmentioning

confidence: 59%

Ultrasound (US)-activated redox dyshomeostasis therapy reinforced by immunogenic cell death (ICD) through a mitochondrial targeting liposomal nanosystem

et al. 2021

View full text Add to dashboard Cite

Introduction: An imbalance in redox homeostasis consistently inhibits tumor cell proliferation and further causes tumor regression. Thus, synchronous glutaminolysis inhibition and intracellular reactive oxygen (ROS) accumulation cause severe redox dyshomeostasis, which may potentially become a new therapeutic strategy to effectively combat cancer. Methods: Mitochondrial-targeting liposomal nanoparticles (abbreviated MLipRIR NPs) are synthesized by the encapsulation of R162 (inhibitor of glutamate dehydrogenase 1 [GDH1]) and IR780 (a hydrophobic sonosensitizer) within the lipid bilayer, which are exploited for ultrasound (US)-activated tumor dyshomeostasis therapy reinforced by immunogenic cell death (ICD). Results: R162 released from MLipRIR NPs disrupts the glutaminolysis pathway in mitochondria, resulting in downregulated enzymatic activity of glutathione peroxidase (GPx). In addition, loaded IR780 can generate high levels of ROS under US irradiation, which not only interrupts mitochondrial respiration to induce apoptosis but also consumes local glutathione (GSH). GSH depletion accompanied by GPx deactivation causes severe ferroptosis of tumor cells through the accumulation of lipid peroxides. Such intracellular redox dyshomeostasis effectively triggers immunogenic cell death (ICD), which can activate antitumor immunity for the suppression of both primary and distant tumors with the aid of immune checkpoint blockade. Conclusions: Taking advantage of multimodal imaging for therapy guidance, this nanoplatform may potentiate systemic tumor eradication with high certainty. Taken together, this state-of-the-art paradigm may provide useful insights for cancer management by disrupting redox homeostasis.

show abstract

Section: Resultsmentioning

confidence: 59%

Ultrasound (US)-activated redox dyshomeostasis therapy reinforced by immunogenic cell death (ICD) through a mitochondrial targeting liposomal nanosystem

et al. 2021

View full text Add to dashboard Cite

show abstract

“…[ 126 ] The system was also modified by triphenylphosphine (TPP) for mitochondria‐targeted delivery. [ 128 ]…”

Section: Construction Of Liposomal Systems For Pdtmentioning

confidence: 99%

“…[126] The system was also modified by triphenylphosphine (TPP) for mitochondriatargeted delivery. [128] Thermo-sensitive liposomes are activated by photothermal effects, where liposomes are self-assembled by lipids and other additives depending on the stability of lipids under the lipid phase transition temperature. This means that liposomes will be destabilized and release cargoes at the desired site once the actual temperature is higher than the phase transition temperature by controlled heating.…”

Section: Activatable Liposomes For Cargos Releasementioning

confidence: 99%

“…[139] Unlike the typical PDT working with three essential elements (light, PS, and oxygen), X-ray-induced PDT has overcome the reliance on light, which has excellent tissue penetration ability compared with only up to 3 mm penetration of red light (620-750 nm) required by verteporfin activation. [128] The mitochondria-targeted liposomes (TPP-Lipo-VP-10Au) encapsulated PS verteporfin and gold nanoparticles. The results indicated that 1 O 2 generation was enhanced by ≈129% and 186% by gold nanoparticles with diameters of 5 and 10 nm, respectively, in the presence of X-rays (4 Gy).…”

Section: Enhancing Tissue-penetration Of Pdtmentioning

confidence: 99%

See 1 more Smart Citation

Multi‐Functional Liposome: A Powerful Theranostic Nano‐Platform Enhancing Photodynamic Therapy

et al. 2021

View full text Add to dashboard Cite

Although photodynamic therapy (PDT) has promising advantages in almost non‐invasion, low drug resistance, and low dark toxicity, it still suffers from limitations in the lipophilic nature of most photosensitizers (PSs), short half‐life of PS in plasma, poor tissue penetration, and low tumor specificity. To overcome these limitations and enhance PDT, liposomes, as excellent multi‐functional nano‐carriers for drug delivery, have been extensively studied in multi‐functional theranostics, including liposomal PS, targeted drug delivery, controllable drug release, image‐guided therapy, and combined therapy. This review provides researchers with a useful reference in liposome‐based drug delivery.

show abstract

“…The organelle mitochondria have been reported to be the most effective subcellular targets in PDT because ROS-induced mitochondrial DNA damage results in cytotoxicity in the PDT treatment [22]. Therefore, the desirable photosensitizers or their delivery carriers are usually expected to be accumulated within or stay close to mitochondria [23].…”

Section: Cellular Localization Of Drugsmentioning

confidence: 99%

Self-assembled Camptothecin derivatives – Curcuminoids conjugate for combinatorial chemo-photodynamic therapy to enhance anti-tumor efficacy

Guo

Xiao

et al. 2021

Journal of Photochemistry and Photobiology B: Biology

View full text Add to dashboard Cite

Camptothecin (CPT), an alkaloid, was first discovered from plants and has potent anti-tumor activity. Since then, CPT analogs (namely Irinotecan and Topotecan) have been approved by the FDA for cancer treatments. Curcumin, on the other hand, is a widely used photosensitizer in photodynamic therapy (PDT) treatment. In our previous work, we have reported a straightforward strategy to construct a drug self-delivery system in which two-molecular species Irinotecan and Curcumin can self-assembly into a complex of ion pairs, namely ICN, through intermolecular noncovalent interactions. We found that ICN has slightly better chemotherapy efficacy than its individual components with much fewer side effects. In this paper, we aim to combine the chemotherapy and the PDT of ICN to further improve its anti-tumor performance. The efficient cellular uptake of ICNs was observed by confocal microscopy. Dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay was used to detect the generation of singlet oxygen species. We found that the cell viability was 9% with both chemotherapy and PDT, and 31% with chemotherapy alone for the case with an ICN concentration of 10 μM, which demonstrated that the anti-tumor efficacy against the HT-29 cancer cell line was enhanced substantially with the combination therapy strategy. The study with an in vivo mouse model has further verified that the chemo-PDT dual therapy can inhibit tumor growth by 84% and 18.8% comparing with the control group and the chemotherapy group, respectively. Our results demonstrated that the new strategy using selfassembly and carrier-free nanoparticles with their chemo-PDT dual therapy may provide new opportunities to develop future combinatorial therapy methods in treating cancer.

show abstract

X-ray induced photodynamic therapy (PDT) with a mitochondria-targeted liposome delivery system

Cited by 39 publications

References 44 publications

Ultrasound (US)-activated redox dyshomeostasis therapy reinforced by immunogenic cell death (ICD) through a mitochondrial targeting liposomal nanosystem

Ultrasound (US)-activated redox dyshomeostasis therapy reinforced by immunogenic cell death (ICD) through a mitochondrial targeting liposomal nanosystem

Multi‐Functional Liposome: A Powerful Theranostic Nano‐Platform Enhancing Photodynamic Therapy

Self-assembled Camptothecin derivatives – Curcuminoids conjugate for combinatorial chemo-photodynamic therapy to enhance anti-tumor efficacy

Contact Info

Product

Resources

About