RGD modified albumin nanospheres for tumour vasculature targeting

Abstract Cancer therapies result in the killing of cancer cells but remain largely ineffective, with most patients dying of their disease. The methodology described here is a new image-guided cancer treatment under development that relies on physical methods to alter tumour biology. It enhances tumour responses to radiation significantly by synergistically destroying tumour blood vessels using microbubbles. It achieves tumour specificity by confining the ultrasonic fields that stimulate microbubbles to tumour location only. By perturbing tumour vasculature and activating specific genetic pathways in endothelial cells, the technique has been demonstrated to sensitise the targeted tissues to subsequent therapeutic application of radiation, resulting in significantly enhanced cell killing through a ceramide-dependent pathway initiated at the cell membrane. The treatment reviewed here destroys blood vessels, significantly enhancing the anti-vascular effect of radiation and improving tumour cure. The significant enhancement of localised tumour cell kill observed with this method means that radiation-based treatments can be potentially made more potent and lower doses of radiation utilised. The technique has the potential to have a profound impact on the practice of radiation oncology by offering a novel and safe means of reducing normal tissue toxicity while at the same time significantly increasing treatment effectiveness.

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In vivo efficacy of HSV-TK transcriptionally targeted to the tumour vasculature is augmented by combination with cytotoxic chemotherapy

The Journal of Gene Medicine ◽

10.1002/jgm.662 ◽

2005 ◽

Vol 7 (3) ◽

pp. 263-275 ◽

Cited By ~ 15

Author(s):

Georgia Mavria ◽

Kevin J. Harrington ◽

Christopher J. Marshall ◽

Colin D. Porter

Keyword(s):

Cytotoxic Chemotherapy ◽

In Vivo Efficacy ◽

Tumour Vasculature

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Targeting Microenvironment of Melanoma and Head and Neck Cancers in Photodynamic Therapy

Current Medicinal Chemistry ◽

10.2174/0929867328666210709113032 ◽

2021 ◽

Vol 28 ◽

Author(s):

Ivana Ratkaj ◽

Martina Mušković ◽

Nela Malatesti

Keyword(s):

Photodynamic Therapy ◽

Head And Neck ◽

Tumour Progression ◽

Neck Region ◽

Angiogenesis Inhibitors ◽

Tumour Microenvironment ◽

Head And Neck Cancers ◽

Skin Cancers ◽

Tumour Vasculature ◽

Optimal Drug

Background: Photodynamic therapy (PDT), in comparison to other skin cancers, is still far less effective for melanoma, due to the strong absorbance and the role of melanin in cytoprotection. The tumour microenvironment (TME) has a significant role in tumour progression, and the hypoxic TME is one of the main reasons for melanoma progression to metastasis and its resistance to PDT. Hypoxia is also a feature of solid tumours in the head and neck region that indicates a negative prognosis. Objective: The aim of this study was to individuate and describe systematically the main strategiesthe main strategies systematically in targeting the TME, especially hypoxia, in PDT against melanoma and head and neck cancers (HNC), and assess the current success in their application. Methods: PubMed, was used for searching, in MEDLINE and other databases were used for searching, for the most recent publications on PDT against melanoma and HNC in combination with the TME targeting and hypoxia. Results: In PDT for melanoma and HNC, it is very important to control hypoxia levels, and, amongst the different approaches, oxygen self-supply systems are often applied. Vascular targeting is promising, but to improve it, optimal drug-light interval, and formulation to increase the accumulation of the photosensitiser in the tumour vasculature, have to be established. On the other side, the use of angiogenesis inhibitors, such as those interfering with VEGF signalling are somewhat less successful than expected and need to be further investigated. Conclusion: Combination The combination of PDT with immunotherapy by using multifunctional nanoparticles continues to develop and seems to be the most promising for achieving a complete and lasting antitumour effect.

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Tumour-vasculature development via endothelial-to-mesenchymal transition after radiotherapy controls CD44v6+ cancer cell and macrophage polarization

Nature Communications ◽

10.1038/s41467-018-07470-w ◽

2018 ◽

Vol 9 (1) ◽

Cited By ~ 25

Author(s):

Seo-Hyun Choi ◽

A-Ram Kim ◽

Jae-Kyung Nam ◽

Jin-Mo Kim ◽

Jee-Youn Kim ◽

...

Keyword(s):

Cancer Cell ◽

Macrophage Polarization ◽

Mesenchymal Transition ◽

Tumour Vasculature ◽

Endothelial To Mesenchymal Transition

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Abnormal morphology biases haematocrit distribution in tumour vasculature and contributes to heterogeneity in tissue oxygenation

10.1101/640060 ◽

2019 ◽

Cited By ~ 1

Author(s):

Miguel O. Bernabeu ◽

Jakub Köry ◽

James A. Grogan ◽

Bostjan Markelc ◽

Albert Beardo ◽

...

Keyword(s):

Therapeutic Efficacy ◽

Tissue Oxygenation ◽

Solid Tumours ◽

Tumour Tissue ◽

Limiting Factor ◽

Antiangiogenic Agents ◽

Vascular Structure ◽

Vascular Networks ◽

Tumour Vasculature ◽

Proxy Measure

AbstractOxygen heterogeneity in solid tumours is recognised as a limiting factor for therapeutic efficacy. This heterogeneity arises from the abnormal vascular structure of the tumour, but the precise mechanisms linking abnormal structure and compromised oxygen transport are only partially understood. In this paper, we investigate the role that RBC transport plays in establishing oxygen heterogeneity in tumour tissue. We focus on heterogeneity driven by network effects, which are challenging to observe experimentally due to the reduced fields of view typically considered. Motivated by our findings of abnormal vascular patterns linked to deviations from current RBC transport theory, we calculate average vessel lengths and diameters from tumour allografts of three cancer cell lines and observe a substantial reduction in the ratio compared to physiological conditions. Mathematical modelling reveals that small values of the ratio λ (i.e. λ < 6) can bias haematocrit distribution in tumour vascular networks and drive heterogeneous oxygenation of tumour tissue. Finally, we show an increase in the value of λ in tumour vascular networks following treatment with the anti-angiogenic cancer agent DC101. Based on our findings, we propose λ as an effective way of monitoring the efficacy of antiangiogenic agents and as a proxy measure of perfusion and oxygenation in tumour tissue undergoing anti-angiogenic treatment.Significance statementOxygen heterogeneity in solid tumours is recognised as a limiting factor for therapeutic efficacy. This heterogeneity arises from the abnormal tumour vascular structure. We investigate the role that anomalies in RBC transport play in establishing oxygen heterogeneity in tumour tissue. We introduce a metric to characterise tumour vasculature (mean vessel length-to-diameter ratio, λ) and demonstrate how it predicts tissue oxygen heterogeneity. We also report an increase in λ following treatment with the antiangiogenic agent DC101. Together, we propose λ as an effective way of monitoring the action of anti-angiogenic agents and a proxy measure of oxygen heterogeneity in tumour tissue. Unravelling the causal relationship between tumour vascular structure and tissue oxygenation will pave the way for new personalised therapeutic approaches.

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