Current cell processing technologies for gene and cell therapies are often slow, expensive, labor... more Current cell processing technologies for gene and cell therapies are often slow, expensive, labor intensive and are compromised by high cell losses and poor selectivity thus limiting the efficacy and availability of clinical cell therapies. We employ cell-specific on-demand mechanical intracellular impact from laser pulse-activated plasmonic nanobubbles (PNB) to process heterogeneous human cell grafts ex vivo with dual simultaneous functionality, the high cell type specificity, efficacy and processing rate for transfection of target CD3+ cells and elimination of subsets of unwanted CD25+ cells. The developed bulk flow PNB system selectively processed human cells at a rate of up to 100 million cell/minute, providing simultaneous transfection of CD3+ cells with the therapeutic gene (FKBP12(V36)-p30Caspase9) with the efficacy of 77% and viability 95% (versus 12 and 60%, respectively, for standard electroporation) and elimination of CD25+ cells with 99% efficacy. PNB flow technology can...
Chemoradiation is the strongest anti-tumor therapy but in resistant unresectable cancers it often... more Chemoradiation is the strongest anti-tumor therapy but in resistant unresectable cancers it often lacks safety and efficacy. We compared our recently developed cell-level combination approach, quadrapeutics, to chemoradiation therapy to establish pre-clinical data for its biodistribution, safety and efficacy in head and neck squamous cell carcinoma (HNSCC), as a clinically challenging aggressive and resistant cancer. In vitro and in vivo models of four carcinomas were treated with standard chemoradiation and quadrapeutics using identical drug and radiation doses. We applied liposomal cisplatin or doxorubicin, colloidal gold, near-infrared laser pulses and radiation, all at low safe doses. The final evaluation used a xenograft model of HNSCC. Quadrapeutics enhanced standard chemoradiation in vitro by reducing head and neck cancer cell proliferation by 1000-fold, inhibiting tumor growth in vivo by 34-fold and improving animal survival by 5-fold, and reducing the side effects to a negl...
Proceedings of the National Academy of Sciences, 2013
Significance We report a noninvasive rapid transdermal detection of malaria infection without dra... more Significance We report a noninvasive rapid transdermal detection of malaria infection without drawing blood or using any reagents. Our method uses harmless laser pulses to generate and detect through the skin tiny vapor nanobubbles specifically in malaria parasites in a patient’s body. This method is distinct from all previous diagnostic approaches, which all rely upon using a needle to obtain blood, require reagents to detect the infection, and are time- and labor-consuming. This nanobubble transdermal detection adds a new dimension to malaria diagnostics and can in the future support the rapid, high-throughput, and high-sensitive diagnosis and screening by nonmedical personnel under field conditions, including the detection of early and asymptomatic disease.
Current cell processing technologies for gene and cell therapies are often slow, expensive, labor... more Current cell processing technologies for gene and cell therapies are often slow, expensive, labor intensive and are compromised by high cell losses and poor selectivity thus limiting the efficacy and availability of clinical cell therapies. We employ cell-specific on-demand mechanical intracellular impact from laser pulse-activated plasmonic nanobubbles (PNB) to process heterogeneous human cell grafts ex vivo with dual simultaneous functionality, the high cell type specificity, efficacy and processing rate for transfection of target CD3+ cells and elimination of subsets of unwanted CD25+ cells. The developed bulk flow PNB system selectively processed human cells at a rate of up to 100 million cell/minute, providing simultaneous transfection of CD3+ cells with the therapeutic gene (FKBP12(V36)-p30Caspase9) with the efficacy of 77% and viability 95% (versus 12 and 60%, respectively, for standard electroporation) and elimination of CD25+ cells with 99% efficacy. PNB flow technology can...
Chemoradiation is the strongest anti-tumor therapy but in resistant unresectable cancers it often... more Chemoradiation is the strongest anti-tumor therapy but in resistant unresectable cancers it often lacks safety and efficacy. We compared our recently developed cell-level combination approach, quadrapeutics, to chemoradiation therapy to establish pre-clinical data for its biodistribution, safety and efficacy in head and neck squamous cell carcinoma (HNSCC), as a clinically challenging aggressive and resistant cancer. In vitro and in vivo models of four carcinomas were treated with standard chemoradiation and quadrapeutics using identical drug and radiation doses. We applied liposomal cisplatin or doxorubicin, colloidal gold, near-infrared laser pulses and radiation, all at low safe doses. The final evaluation used a xenograft model of HNSCC. Quadrapeutics enhanced standard chemoradiation in vitro by reducing head and neck cancer cell proliferation by 1000-fold, inhibiting tumor growth in vivo by 34-fold and improving animal survival by 5-fold, and reducing the side effects to a negl...
Proceedings of the National Academy of Sciences, 2013
Significance We report a noninvasive rapid transdermal detection of malaria infection without dra... more Significance We report a noninvasive rapid transdermal detection of malaria infection without drawing blood or using any reagents. Our method uses harmless laser pulses to generate and detect through the skin tiny vapor nanobubbles specifically in malaria parasites in a patient’s body. This method is distinct from all previous diagnostic approaches, which all rely upon using a needle to obtain blood, require reagents to detect the infection, and are time- and labor-consuming. This nanobubble transdermal detection adds a new dimension to malaria diagnostics and can in the future support the rapid, high-throughput, and high-sensitive diagnosis and screening by nonmedical personnel under field conditions, including the detection of early and asymptomatic disease.
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Papers by Dmitri Lapotko