Prostate-specific membrane antigen (PSMA)-targeted photodynamic therapy enhances the delivery of PSMA-targeted magnetic nanoparticles to PSMA-expressing prostate tumors

Ngen, Ethel J.; Chen, Ying; Azad, Babak Behnam; Boinapally, Srikanth; Jacob, Desmond; Lisok, Ala; Shen, Ce; Hossain, Mir Shanaz; Jin, Jiefu; Bhujwalla, Zaver M.; Pomper, Martin G.; Banerjee, Sangeeta Ray

doi:10.7150/ntno.52361

Cited by 14 publications

(17 citation statements)

References 57 publications

(61 reference statements)

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“…However, PC-3 PIP cells were inoculated to mice in medium in the study by Tschan et al [ 25 ], whereas PC-3 PIP cells were inoculated in medium:Matrigel matrix (1:1) in the present study (like for C4-2 cells; [ 16 ]), resulting in a very rapid PC-3 PIP tumor growth ( Figure S12 ). This may influence tumor stroma and vascular density, and, thus, radioligand uptake because vascular density tends to decrease with tumor growth [ 41 , 42 ]. Ngen et al found that higher vascular density enhanced delivery of their PSMA-targeted nanoparticles in the PC-3 PIP tumor peripheries compared to reduced delivery in the low vascularized areas in the centers of the tumor [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

“…This may influence tumor stroma and vascular density, and, thus, radioligand uptake because vascular density tends to decrease with tumor growth [ 41 , 42 ]. Ngen et al found that higher vascular density enhanced delivery of their PSMA-targeted nanoparticles in the PC-3 PIP tumor peripheries compared to reduced delivery in the low vascularized areas in the centers of the tumor [ 41 ]. In the present study, a less blood-rich stroma was observed throughout the whole cross-section of the PC-3 PIP tumor ( Figure 5 ).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, PSMA is a regulator of new blood vessel formation (i.e., angiogenesis) [ 39 , 40 ]. Ngen et al detected higher vascular densities and blood vessels of larger diameters at the tumor peripheries compared to the tumor centers of PC-3 PIP tumors, and found that the intratumoral vascular density and distribution pattern influenced the delivery and distribution of their PSMA-targeted nanoparticles [ 41 ]. In addition, rapid tumor growth may influence radioligand uptake because vascular density tends to decrease as the tumor grows, leading to zones of hypoxia and eventually necrosis as tumors “outgrow” their blood supply [ 42 ].…”

Section: Introductionmentioning

confidence: 99%

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Factors Influencing the Therapeutic Efficacy of the PSMA Targeting Radioligand 212Pb-NG001

Stenberg

Tornes

Nilsen

et al. 2022

Cancers

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This study aimed to determine the influence of cellular PSMA expression, radioligand binding and internalization, and repeated administrations on the therapeutic effects of the PSMA-targeting radioligand 212Pb-NG001. Cellular binding and internalization, cytotoxicity, biodistribution, and the therapeutic efficacy of 212Pb-NG001 were investigated in two human prostate cancer cell lines with different PSMA levels: C4-2 (PSMA+) and PC-3 PIP (PSMA+++). Despite 10-fold higher PSMA expression on PC-3 PIP cells, cytotoxicity and therapeutic efficacy of the radioligand was only 1.8-fold better than for the C4-2 model, possibly explained by lower cellular internalization and less blood-rich stroma in PC-3 PIP xenografts. Mice bearing subcutaneous PC-3 PIP xenografts were treated with 0.2, 0.4, and 0.8 MBq of 212Pb-NG001 that resulted in therapeutic indexes of 2.7, 3.0, and 3.5, respectively. A significant increase in treatment response was observed in mice that received repeated injections compared to the corresponding single dose (therapeutic indexes of 3.6 for 2 × 0.2 MBq and 4.4 for 2 × 0.4 MBq). The results indicate that 212Pb-NG001 can induce therapeutic effects at clinically transferrable doses, both in the C4-2 model that resembles solid tumors and micrometastases with natural PSMA expression and in the PC-3 PIP model that mimics poorly vascularized metastases.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Factors Influencing the Therapeutic Efficacy of the PSMA Targeting Radioligand 212Pb-NG001

Stenberg

Tornes

Nilsen

et al. 2022

Cancers

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“…Zimmer 1995, 40 Wu 2019, 41 Ngen 2021, 42 Glover 2020, 43 Mathiasen 2019, 44 Schilham 2021, 45 Toth 2017, 46 Barajas 2019 47 Kelly 2020, 52 Rowe 2015, 53 Gorin 2016, 54 Rowe 2017, 55 Wilson 2020 56 PET Specific molecular targets; metabolism (glucose/glutamine) High sensitivity and potential for high specificity/complex infrastructure; costly agents (translational, clinical)…”

Section: Optical Techniquesmentioning

confidence: 99%

Molecular imaging in oncology: Current impact and future directions

Rowe

Pomper

2021

CA A Cancer J Clinicians

Self Cite

150

111

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The authors define molecular imaging, according to the Society of Nuclear Medicine and Molecular Imaging, as the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in humans and other living systems. Although practiced for many years clinically in nuclear medicine, expansion to other imaging modalities began roughly 25 years ago and has accelerated since. That acceleration derives from the continual appearance of new and highly relevant animal models of human disease, increasingly sensitive imaging devices, high-throughput methods to discover and optimize affinity agents to key cellular targets, new ways to manipulate genetic material, and expanded use of cloud computing. Greater interest by scientists in allied fields, such as chemistry, biomedical engineering, and immunology, as well as increased attention by the pharmaceutical industry, have likewise contributed to the boom in activity in recent years. Whereas researchers and clinicians have applied molecular imaging to a variety of physiologic processes and disease states, here, the authors focus on oncology, arguably where it has made its greatest impact. The main purpose of imaging in oncology is early detection to enable interception if not prevention of full-blown disease, such as the appearance of metastases. Because biochemical changes occur before changes in anatomy, molecular imaging-particularly when combined with liquid biopsy for screening purposes-promises especially early localization of disease for optimum management. Here, the authors introduce the ways and indications in which molecular imaging can be undertaken, the tools used and under development, and near-term challenges and opportunities in oncology.

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“…IRDye700DX is a hydrophilic phthalocyanine that readily forms conjugates with primary and secondary amino groups in targeting moieties, e.g., Cet [15][16][17][18]. An IRDye700DX-Cetconjugate has been given fast-track recognition by regulators in the USA and Japan [19].…”

Section: Introductionmentioning

confidence: 99%

Photosensitive EGFR-Targeted Nanocarriers for Combined Photodynamic and Local Chemotherapy

et al. 2022

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The major limitation of any cancer therapy lies in the difficulty of precisely controlling the localization of the drug in the tumor cells. To improve this drawback, our study explores the use of actively-targeted chemo-photo-nanocarriers that recognize and bind to epidermal growth factor receptor-overexpressing cells and promote the local on-demand release of the chemotherapeutic agent doxorubicin triggered by light. Our results show that the attachment of high concentrations of doxorubicin to cetuximab-IRDye700DX-mesoporous silica nanoparticles yields efficient and selective photokilling of EGFR-expressing cells mainly through singlet oxygen-induced release of the doxorubicin from the nanocarrier and without any dark toxicity. Therefore, this novel triply functionalized nanosystem is an effective and safe nanodevice for light-triggered on-demand doxorubicin release.

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Prostate-specific membrane antigen (PSMA)-targeted photodynamic therapy enhances the delivery of PSMA-targeted magnetic nanoparticles to PSMA-expressing prostate tumors

Cited by 14 publications

References 57 publications

Factors Influencing the Therapeutic Efficacy of the PSMA Targeting Radioligand 212Pb-NG001

Factors Influencing the Therapeutic Efficacy of the PSMA Targeting Radioligand 212Pb-NG001

Molecular imaging in oncology: Current impact and future directions

Photosensitive EGFR-Targeted Nanocarriers for Combined Photodynamic and Local Chemotherapy

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