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DRUG CLASS:

Reactive oxygen species stimulant

2d
Enrollment closed • Enrollment change
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Opdivo (nivolumab) • Photofrin (porfimer sodium)
13d
Signaling Mechanism of Cuproptosis Activating cGAS-STING Immune Pathway. (PubMed, JACS Au)
With Cu-DPPZ-Py+ and Cu-Elesclomol, there is strong evidence that the triggering cuproptosis significantly drives mitochondrial DNA (mtDNA) release to activate innate immunity via cyclic GMP-AMP synthase-stimulation of interferon genes (cGAS-STING), which can improve T cell antitumor immunity in vivo. By contrast, it is observed that Cu-DPPZ-Ph treated tumor cells could release intracellular caspase-3, resulting in apoptosis-associated immunosuppression. This study supports insights into how cuproptosis bridges cGAS-STING immune pathways, contributing to the development of cuproptosis-based antitumor immunotherapy.
Journal
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STING (stimulator of interferon response cGAMP interactor 1) • CASP3 (Caspase 3) • CGAS (Cyclic GMP-AMP Synthase)
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elesclomol (STA-4783)
24d
Panax Notoginseng Saponins promotes the meningeal lymphatic system-mediated hematoma absorption in intracerebral hemorrhage. (PubMed, Phytomedicine)
PNS might be effective for ICH treatment by enhancing lymphangiogenesis and the meningeal lymphatic drainage function, thereby attenuating inflammation and promoting neurological recovery. The role of PNS in regulation of MLVs was investigated for the first time. This study provides a novel insight for PNS in the medical therapy of ICH.
Journal
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TNFA (Tumor Necrosis Factor-Alpha)
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Visudyne (verteporfin)
29d
New P2 trial
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belzupacap sarotalocan (AU-011)
1m
Screening of photosensitizers-ATP binding cassette (ABC) transporter interactions in vitro. (PubMed, Cancer Drug Resist)
The ABCG2 inhibitor (fumitremorgin C) and P-gp inhibitor (valspodar) effectively blocked the transport mediated by ABCG2 and P-gp of rose bengal and BPD... In summary, our study provided new knowledge that temoporfin, talaporfin sodium, methylene blue, and indocyanine green are not substrates of ABCG2, P-gp, or MRP1...Rose bengal is a substrate of ABCG2, P-gp, and MRP1. The results presented here indicate ABC transporter substrate status as a possible cause for cellular resistance to photodynamic therapy with rose bengal, redaporfin, and BPD.
Preclinical • Journal
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ABCB1 (ATP Binding Cassette Subfamily B Member 1) • ABCG2 (ATP Binding Cassette Subfamily G Member 2) • ABCC1 (ATP Binding Cassette Subfamily C Member 1)
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Foscan (temoporfin) • Litx (talaporfin)
1m
Statins, Cholesterol and Cognitive Decline in Alzheimer's (clinicaltrials.gov)
P=N/A, N=1000, Not yet recruiting, Karolinska Institutet
New trial
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elesclomol (STA-4783)
1m
Drug repositioning identifies potential autophagy inhibitors for the LIR motif p62/SQSTM1 protein. (PubMed, Comput Biol Chem)
The results revealed that the kanamycin, velpatasvir, verteporfin, and temoporfin significantly decreased the binding of LIR to the p62 protein. Finally, we experimentally confirmed that Kanamycin can inhibit autophagy-associated acidic vesicular formation in breast cancer MCF-7 and MDA-MB 231 cells. These repositioned drugs may represent novel autophagy modulators in clinical management, warranting further investigation.
Journal
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SQSTM1 (Sequestosome 1)
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Visudyne (verteporfin) • Foscan (temoporfin)
2ms
RNA sequencing identifies lung cancer lineage and facilitates drug repositioning. (PubMed, PeerJ)
Our results indicated that dinaciclib and alvocidib exhibited similar activity and sensitivity in the neuroendocrine cluster. Also, a lineage factor named KLF5 recognized by inferred transcriptional factors activity could be suppressed by verteporfin.
Journal • IO biomarker
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STK11 (Serine/threonine kinase 11)
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STK11 mutation
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Visudyne (verteporfin) • alvocidib (DSP-2033) • dinaciclib (MK-7965)
2ms
Cuproptosis in microsatellite stable colon cancer cells affects the cytotoxicity of CD8+T through the WNT signaling pathway. (PubMed, Chem Biol Interact)
The study developed an MSS CC cuproptosis model using 50 nM elesclomol and 1 μM CuCl2...Cuproptosis in MSS CC cells enhances the cytotoxicity of CD8+ T cells, which may be achieved through downregulation of the WNT signaling pathway and decreased expression of PD-L1. In the future, drugs that can induce cuproptosis may be a promising approach to improve MSS CC immunotherapy.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8)
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PD-L1 expression
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elesclomol (STA-4783)
2ms
AB017. NFκB1 regulates FDX1 to facilitate elesclomol-induced cuproptosis against glioblastoma. (PubMed, Chin Clin Oncol)
Elesclomol inhibits glioblastoma development via inducing cuproptosis, regulated by NFκB1/FDX1 axis.
Journal • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • SLC7A11 (Solute Carrier Family 7 Member 11) • ATP7A (ATPase Copper Transporting Alpha) • DLAT (Dihydrolipoamide S-Acetyltransferase) • FDX1 (Ferredoxin 1)
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elesclomol (STA-4783)
2ms
Enrollment open • Enrollment change
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Visudyne (verteporfin)
2ms
Photodynamic Therapy to Amplify the Response to Immunotherapy in Patients With Non-small Cell Lung Cancer With Pleural Disease (clinicaltrials.gov)
P1, N=5, Active, not recruiting, Roswell Park Cancer Institute | Suspended --> Active, not recruiting | N=16 --> 5 | Trial completion date: Mar 2025 --> Jan 2026 | Trial primary completion date: Mar 2025 --> Feb 2024
Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date
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PD-L1 (Programmed death ligand 1)
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PD-L1 expression
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Photofrin (porfimer sodium)
2ms
Exploring the prognosis value, immune correlation, and drug responsiveness prediction of homeobox C6 (HOXC6) in lung adenocarcinoma. (PubMed, Discov Oncol)
Taken together, there is a great potential for HOXC6 to become a prognosis biomarker and contribute to develop treatment strategies for LUAD patients. Further mechanism exploration and drug development for HOXC6 are needed.
Journal
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HOXC6 (Homeobox C6)
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docetaxel • cytarabine • Torisel (temsirolimus) • sirolimus • Zolinza (vorinostat) • elesclomol (STA-4783)
2ms
The signature genes of cuproptosis associates with tumor immune microenvironment and predicts prognosis in kidney renal clear cell carcinoma. (PubMed, Front Oncol)
Cell experiments were conducted to verify whether FDX1 was involved in cuproptosis of Caki-1 cells induced by Elesclomol...This study provides compelling evidence that cuproptosis is closely linked to the prognosis of KIRC. FDX1 holds promise as a viable biomarker and therapeutic target for assessing the effectiveness of tumor immunotherapy in KIRC.
Journal • IO biomarker
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FDX1 (Ferredoxin 1)
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elesclomol (STA-4783)
3ms
IL-32 aggravates metabolic disturbance in human nucleus pulposus cells by activating FAT4-mediated Hippo/YAP signaling. (PubMed, Int Immunopharmacol)
Lentivirus overexpressing IL-32 or knocking down Fat atypical cadherin 4 (FAT4), yes-associated protein (YAP) inhibitor-Verteporfin (VP) were used to treat human NP cells, to explore the pathogenesis of IL-32...Mechanistically, the elevation of IL-32 in the inflammatory microenvironment enhanced its interactions with FAT4 and mammalian sterile 20-like kinase1/2 (MST1/2) proteins, prompting MST1/2 phosphorylation, and activating the Hippo/YAP signaling pathway, causing matrix metabolism disorder in NP cells. Our results suggest that IL-32 mediates matrix metabolism disorders in NP cells in the inflammatory micro-environment via the FAT4/MST/YAP axis, providing a theoretical basis for the precise treatment of IDD.
Journal
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TNFA (Tumor Necrosis Factor-Alpha) • FAT4 (FAT Atypical Cadherin 4) • IL32 (Interleukin 32)
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Visudyne (verteporfin)
3ms
Trial completion • Trial completion date
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belzupacap sarotalocan (AU-011)
3ms
BOLD-100-001: BOLD-100 in Combination With FOLFOX for the Treatment of Advanced Solid Tumours (clinicaltrials.gov)
P1/2, N=220, Recruiting, Bold Therapeutics, Inc. | Active, not recruiting --> Recruiting | Phase classification: P1b/2a --> P1/2 | N=117 --> 220 | Trial completion date: Sep 2024 --> Sep 2026 | Trial primary completion date: Dec 2023 --> Jun 2026
Enrollment open • Phase classification • Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • Metastases
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5-fluorouracil • leucovorin calcium • BOLD-100
3ms
Mechanism and rational combinations with GP-2250, a novel oxathiazine derivative, in ovarian cancer. (PubMed, Cancer Med)
Taken together, our data indicate that GP-2250 exerts profound effects on tumor metabolism and, in combination with PARP inhibitors or bevacizumab, showed promising anti-tumor efficacy. These findings could have implications for the clinical development of GP-2250.
Journal • PARP Biomarker
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HIF1A (Hypoxia inducible factor 1, alpha subunit) • HK2 (Hexokinase 2) • ANXA5 (Annexin A5)
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Avastin (bevacizumab) • cisplatin • paclitaxel • topotecan • misetionamide (GP-2250)
3ms
Phase II Trial of Radical Pleurectomy With or Without Intraoperative PDT for Malignant Pleural Mesothelioma (clinicaltrials.gov)
P2, N=102, Recruiting, Abramson Cancer Center at Penn Medicine | Trial completion date: Dec 2024 --> Jun 2025 | Trial primary completion date: May 2024 --> Dec 2024
Trial completion date • Trial primary completion date
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Photofrin (porfimer sodium)
3ms
Photoradiation With Verteporfin to Facilitate Immunologic Activity of Pembrolizumab in Unresectable, Locally Advanced or Metastatic Pancreatic Cancer (clinicaltrials.gov)
P2, N=25, Not yet recruiting, Mayo Clinic | Trial completion date: Jul 2029 --> Oct 2029 | Initiation date: Jun 2024 --> Oct 2024 | Trial primary completion date: Jul 2029 --> Oct 2029
Trial completion date • Trial initiation date • Trial primary completion date • Metastases
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Keytruda (pembrolizumab) • oxaliplatin • irinotecan • leucovorin calcium • Visudyne (verteporfin) • fluorouracil topical
3ms
Endobronchial Ultrasound Guided Interstitial Photodynamic Therapy in Treating Patients With Locally Advanced Lung Cancer (clinicaltrials.gov)
P1/2, N=19, Active, not recruiting, Roswell Park Cancer Institute | Recruiting --> Active, not recruiting | N=65 --> 19 | Trial primary completion date: Feb 2030 --> Nov 2023
Enrollment closed • Enrollment change • Trial primary completion date • Endobronchial ultrasound • Metastases
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Photofrin (porfimer sodium)
4ms
Ruthenium drug BOLD-100 regulates BRAFMT colorectal cancer cell apoptosis through AhR/ROS/ATR signaling axis modulation. (PubMed, Mol Cancer Res)
These results unveil possible novel therapeutic opportunity for BRAFMT CRC. Implications: BOLD-100 induces BRAFMT-dependent replication stress, and targeted strategies against replication stress (eg. by using ATR inhibitors) in combination with BOLD-100 may serve as a potential novel therapeutic strategy for clinically aggressive BRAFMT CRC.
Journal
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CHEK1 (Checkpoint kinase 1) • CYP1A1 (Cytochrome P450 Family 1 Subfamily A Member 1)
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BOLD-100
4ms
Adaptor protein CEMIP reduces the chemosensitivity of small cell lung cancer via activation of an SRC-YAP oncogenic module. (PubMed, Acta Pharmacol Sin)
Through the GDSC database, we found that CEMIP expression levels were positively correlated with the IC50 values of several commonly used chemotherapeutic drugs in SCLC cells (cisplatin, gemcitabine, 5-fluorouracil and cyclophosphamide). The combination of the SRC inhibitor dasatinib or the YAP inhibitor verteporfin and cisplatin/etoposide (EP regimen) displayed excellent synergistic antitumor effects on SCLC both in vitro and in vivo. This study demonstrated that targeted therapy against the CEMIP/SRC/YAP complex is a potential strategy for SCLC and provides a rationale for the development of future clinical trials with translational prospects.
Journal
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CEMIP (Cell Migration Inducing Hyaluronidase 1)
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cisplatin • dasatinib • gemcitabine • 5-fluorouracil • cyclophosphamide • etoposide IV • Visudyne (verteporfin)
4ms
A novel signature constructed by cuproptosis-related RNA methylation regulators suggesting downregulation of YTHDC2 may induce cuproptosis resistance in colorectal cancer. (PubMed, Int Immunopharmacol)
We developed a prognostic model constructed by 6 CRRMRs to assess overall survival and immune microenvironment of CRC patients. YTHDC2 might regulate cuproptosis in multiple ways.
Journal • Tumor mutational burden
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TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • YTHDC2 (YTH N6-Methyladenosine RNA Binding Protein C2)
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elesclomol (STA-4783)
4ms
Dysregulated Wnt/β-catenin signaling confers resistance to cuproptosis in cancer cells. (PubMed, Cell Death Differ)
Knockdown of TCF4 or pharmacological Wnt/β-catenin blockade increased the sensitivity of CSCs to elesclomol-Cu-induced cuproptosis. These findings reveal a link between copper homeostasis regulated by the Wnt/β-catenin pathway and cuproptosis sensitivity, and suggest a precision medicine strategy for cancer treatment through selective cuproptosis induction.
Journal
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TCF4 (Transcription Factor 4)
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elesclomol (STA-4783)
5ms
Copper(II)-Based Nano-Regulator Correlates Cuproptosis Burst and Sequential Immunogenic Cell Death for Synergistic Cancer Immunotherapy. (PubMed, Biomater Res)
To trigger cuproptosis, copper-ionophore elesclomol (ES) had to be employed for the copper-transporting-mediated process...This enabled an increased infiltration of cytotoxic CD8+ T cells and consequently enhanced antitumor immune responses for successfully suppressing fibrosarcoma growth. Thus, the copper(II)-based metal-organic framework nano-regulator offered a promising approach for inducing cuproptosis and cuproptosis-stimulated ICD for cancer immunotherapy.
Journal
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CD8 (cluster of differentiation 8)
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elesclomol (STA-4783)
5ms
A Physiochemical, In Vitro, and In Vivo Comparative Analysis of Verteporfin-Lipid Conjugate Formulations: Solid Lipid Nanoparticles and Liposomes. (PubMed, ACS Appl Bio Mater)
In this study, we prepared 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)-based solid lipid nanoparticles (LNPs) that stably entrap BPD-PC, which resemble the composition of the SpikevaxⓇ Moderna COVID-19 vaccine, and compared them to a DPPC based liposomal formulation (Lipo BPD-PC). In vivo studies revealed that CT1BA5 tumor fluorescence signals from BPD-PC were 2.41-fold higher with Lipo BPD-PC than with LNP BPD-PC; however, no significant difference was observed in tumor tissue selectivity or tumor penetration. As such, we present LNP BPD-PC as a unique and more stable nanoplatform to carry BPD lipid conjugates, such as BPD-PC, with a potential for future photodynamic immune priming studies and multiagent drug delivery.
Preclinical • Journal • Lipid Nanoparticle
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CALR (Calreticulin)
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Visudyne (verteporfin)
5ms
Long non-coding RNAs in ferroptosis and cuproptosis impact on prognosis and treatment in hepatocellular carcinoma. (PubMed, Clin Exp Med)
Finally, we validated the accuracy of FCRLs in hepatocellular carcinoma cell lines using induction agents (elesclomol and erastin). Cellular assays revealed significant changes in the expression of AC019080.5, AC145207.5, MIR210HG, and LINC01063 in HCC cell lines following the addition of ferroptosis and cuproptosis inducers. We created a signature of four FCRLs that accurately predicted survival in HCC patients, laid the foundation for basic research related to ferroptosis and cuproptosis in hepatocellular carcinoma, and provided therapeutic recommendations for HCC patients.
Journal • IO biomarker
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MIR210HG (MIR210 Host Gene)
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elesclomol (STA-4783) • erastin
5ms
Coumarin-modified ruthenium complexes: Synthesis, characterization, and antiproliferative activity against human cancer cells. (PubMed, Arch Pharm (Weinheim))
Among ruthenium complexes studied as anticancer metallodrugs, NKP-1339, NAMI-A, RM175, and RAPTA-C have already entered clinical trials due to their potent antitumor activity demonstrated in preclinical studies and reduced toxicity in comparison with platinum drugs...Coumarin derivative 2a positively regulated the expression and activity of c-Myc and NPM1 in RKO colon carcinoma cells, while the Ru(II) half-sandwich complex 2cRu induced downregulation of AKT and ERK signaling in PANC-1 cells concomitant with reduced intracellular levels of reactive oxygen species. Altogether, our findings indicated that coumarin-modified half-sandwich Ru(II) complexes held potential as anticancer agents against gastrointestinal malignancies.
Journal
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • NPM1 (Nucleophosmin 1)
|
BOLD-100
5ms
Trial suspension
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PD-L1 (Programmed death ligand 1)
|
Photofrin (porfimer sodium)
6ms
The role of yes activated protein (YAP) in melanoma metastasis. (PubMed, iScience)
YAP activates the expression of the matricellular proteins CCN1 (cyr61) and CCN2 (ctgf), themselves mediators of fibrogenesis and oncogenesis, and coordination of matrix deposition and angiogenesis. This review discusses how therapeutically targeting YAP through YAP inhibitors verteporfin and celastrol and its downstream mediators CCN1 and CCN2 might be useful in treating melanoma.
Review • Journal
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CCN1 (Cellular Communication Network Factor 1) • CTGF (Connective tissue growth factor)
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Visudyne (verteporfin)
6ms
Ferritinophagy mediates adaptive resistance to EGFR tyrosine kinase inhibitors in non-small cell lung cancer. (PubMed, Nat Commun)
Osimertinib (Osi) is a widely used epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). Combining Osi with elesclomol, a copper ion ionophore, significantly increases the efficacy of Osi, with no additional toxicity. Altogether, this study reveals the mechanisms of NCOA4-mediated ferritinophagy in Osi adaptive resistance and introduces a promising new therapy of combining copper ionophores to improve its initial efficacy.
Journal
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EGFR (Epidermal growth factor receptor) • NCOA4 (Nuclear Receptor Coactivator 4)
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Tagrisso (osimertinib) • elesclomol (STA-4783)
6ms
Dysfunctional adipocytes promote tumor progression through YAP/TAZ-dependent cancer-associated adipocyte transformation. (PubMed, Nat Commun)
Treatment with the YAP/TAZ inhibitor, verteporfin, suppresses tumor progression in BaKO and HFD-fed mice, highlighting its efficacy against mice with metabolic dysregulation. Overall, our findings provide insights into the key mediators of CAA and their significance in developing a TME, thereby suggesting a viable approach targeting adipocyte homeostasis to suppress cancer growth.
Journal
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BECN1 (Beclin 1) • TAFAZZIN (Tafazzin)
|
Visudyne (verteporfin)
6ms
Elesclomol-copper synergizes with imidazole ketone erastin by promoting cuproptosis and ferroptosis in myelodysplastic syndromes. (PubMed, Biomed Pharmacother)
Cell viability assays showed that the glutathione and its precursor N-acetylcysteine could significantly rescue the cell death under either mono or combination treatment, demonstrating that GSH acts at the crossing point in the regulation network of cuproptosis and ferroptosis. Significantly, the reconstitution of xCT expression and knockdown of FDX1 cells have been found to contribute to the tolerance of mono treatment but have little recovery impact on the combined treatment. Collectively, these findings suggest that a synergistic interaction leading to the induction of multiple programmed cell death pathways could be a promising approach to enhance the effectiveness of therapy for MDS.
Journal
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DLAT (Dihydrolipoamide S-Acetyltransferase) • FDX1 (Ferredoxin 1)
|
elesclomol (STA-4783) • erastin
6ms
Verteporfin suppressed mitophagy via PINK1/parkin pathway in endometrial cancer. (PubMed, Am J Cancer Res)
This suggests that verteporfin may inhibit mitophagy by elevating ROS levels, thereby inhibiting EC cell viability. The effect of verteporfin on mitophagy supports further investigation as a potential therapeutic option for EC.
Journal
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PINK1 (PTEN Induced Kinase 1)
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Visudyne (verteporfin)
6ms
Interstitial Photodynamic Therapy Following Palliative Radiotherapy in Treating Patients With Inoperable Malignant Central Airway Obstruction (clinicaltrials.gov)
P1/2, N=39, Not yet recruiting, Roswell Park Cancer Institute | Trial completion date: Apr 2029 --> Jul 2029 | Initiation date: Apr 2024 --> Jul 2024 | Trial primary completion date: Apr 2029 --> Jul 2029
Trial completion date • Trial initiation date • Trial primary completion date
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Visudyne (verteporfin)
7ms
Verteporfin inhibits TGF-β signaling by disrupting the Smad2/3-Smad4 interaction. (PubMed, Mol Biol Cell)
Furthermore, VP exhibited inhibitory effects on TGF-β-induced epithelial-mesenchymal transition and cell migration. Our findings indicate a novel approach to develop protein-protein interaction inhibitors of the canonical TGF-β signaling pathway for treatments of related diseases.
Journal
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SMAD4 (SMAD family member 4) • TGFB1 (Transforming Growth Factor Beta 1) • SMAD2 (SMAD Family Member 2)
|
Visudyne (verteporfin)
7ms
A cuproptosis-related signature predicts prognosis and indicates cross-talk with immunocyte in ovarian cancer. (PubMed, Discov Oncol)
This study constructed a new cuproptosis-related gene signature that has a good prognostic capacity in assessing the outcome of OC patients. This study enhances our understanding of cuproptosis associated with ovarian cancer aggressiveness, cross-talk with immunocytes, and serves as a novel chemotherapy strategy.
Journal
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KIF26B (Kinesin Family Member 26B)
|
cisplatin • elesclomol (STA-4783)
7ms
Elesclomol-Cu Induces Cuproptosis in Human Acute Myeloid Leukemia Cells (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)
ES-Cu can induce cuproptosis in AML cells, which provides a new idea for the treatment of AML.
Journal
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DLAT (Dihydrolipoamide S-Acetyltransferase) • DPYD (Dihydropyrimidine Dehydrogenase) • FDX1 (Ferredoxin 1)
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elesclomol (STA-4783)
7ms
New P2 trial • Metastases
|
Keytruda (pembrolizumab) • oxaliplatin • irinotecan • leucovorin calcium • Visudyne (verteporfin) • fluorouracil topical
7ms
Amelioration of NAFLD by sleeve gastrectomy-triggered hepatocyte regeneration in mice - experimental research. (PubMed, Int J Surg)
SG can enhance hepatic regenerative capacity and improve liver metabolism. This study provides a better understanding of the mechanisms underlying SG-induced metabolic improvements.
Preclinical • Journal
|
YES1 (YES Proto-Oncogene 1, Src Family Tyrosine Kinase)
|
Visudyne (verteporfin)
8ms
Modulated Electro-Hyperthermia Accelerates Tumor Delivery and Improves Anticancer Activity of Doxorubicin Encapsulated in Lyso-Thermosensitive Liposomes in 4T1-Tumor-Bearing Mice. (PubMed, Int J Mol Sci)
In this study, we investigated whether mEHT accelerates the tumor-specific delivery of doxorubicin (DOX) from lyso-thermosensitive liposomal doxorubicin (LTLD) and improves its anticancer efficacy in mice bearing a triple-negative breast cancer cell line (4T1)...The body weight loss was similar in all mice treated with any DOX formulation, suggesting no difference in toxicity. In conclusion, LTLD combined with mEHT represents a novel approach for DOX delivery into cancer tissue.
Preclinical • Journal
|
CASP3 (Caspase 3)
|
pegylated liposomal doxorubicin • ThermoDox (lyso-thermosensitive liposomal doxorubicin)