MGMR is well-tolerated by cells

Human stem cells cultured with a range of MGMR™ concentrations do not show reduced viability relative to growth media.

MGMR™ is non-genotoxic

Cells treated with a range of concentrations of MGMR™ do not show evidence of chromosomal aberration relative to positive control.

MGMR™ is non-carcinogenic

In neoplastic transformation analysis, MGMR™ was not shown to significantly transform cells to soft-agar proliferating colonies relative to positive control.

MGMR™ Intracellular Trafficking

PTK2 cells (kidney epithelium)

Intracellular distribution

  • In eukaryotic cells, MGMR™ localizes within the nucleus and actin cytoskeleton

Cellular uptake produces no evidence of cytotoxicity

Potential for delivery of:

  • Genetic materials
  • Antibodies
  • Proteins
  • Enzymes
  • Other membrane-impermeable molecules

MGMR™ is internalized into cells by active transport

MGMR™ is internalized within intercellular vesicles that traffic into the interior of the cell.

Active transport of MGMR™ offers the potential for intercellular delivery of diverse types biomolecules which does not damage plasma membrane integrity and reduces cytotoxicity.

Mechanism of MGMR™ (CNT) Internalization:

  1. MGMR™ Vehicles dispersed in the extracellular space are encapsulated within intracellular vesicles,
  2. Vesicular trafficking into cellular interior,
  3. Vesicular plasma membrane breakdown and release of vehicles into cytosol.

Intracellular peptide transport with MGMR™

In this peptide delivery study, MGMR™ binds a pro-apoptotic peptide with high affinity, transports it across the plasma membrane, and releases it within the cytoplasm, triggering apoptosis. Critically, unloaded MGMR™ does not reduce cellular viability and the peptide alone demonstrates no significant effect.

MGMR™ enables efficient intracellular transport of siRNA

In this siRNA delivery study, siRNA-loaded MGMR™ is readily internalized by cells, ferrying siRNA across the plasma membrane and delivering the payload into the cytosol. Efficiency of siRNA delivery is evaluated by mRNA-level expression of the gene of interest.

MGMR™ Nuclease-loading and Plasmind Digestion

Concurrent Plasmid Digestion

Free Nucleases: Hincll & Scal supplied together Nucleases+MGMR™: Hincll & Scal loaded together on MGMR™ and supplied together

Serial Plasmid Digestion

Free Nucleases: 1st; 2nd Hincll
Nucleases+MGMR™: 1st Scal+MGMR; 2nd Hincll+MGMR™

MGMR™ Nuclease-loading for Serial Plasmid Cleavage

Protocol

  • Scal + MGMR™ incubated with 1ug plasmid for 15 min at 37°C, followed by Hincll + MGMR™ for additional 15 min at 37°C
  • Electrophoresis (70 min) – 1% agarose

Results

  • Individual nucleases loaded on MGMR™ can cleave pDNA in series
  • MGMR™ preserves nuclease activity and demonstrates loading density-depending pDNA cleavage
  • Sequential addition of “free” nucleases without MGMR™ produces very low-efficiency pDNA cleavage
  • Formulation 2 demonstrated greatest efficiency for serial plasmid cleavage relative to Formulation 1 and sequentially added free nucleases

MGMR™ Nuclease-loading for Concurrent Plasmid Cleavage

Protocol

  • Nucleases + MGMR™ incubated with 1ug plasmid for 15 min. at 37°C
  • Electrophoresis (70 min) – 1% agarose

Results

  • Enzyme loading on MGMR™ preserves activity of nucleases
  • Cutting efficiency of nucleases + MGMR™ relates to loading density (unites/ug)
  • Formulations 1 and 2 demonstrate most efficient pDNA cleavage at 2000 units/ug MGMR™

Publications

Read more about MGMR™ in the featured publications below

...
Development of medical-grade, discrete, multi-walled carbon nanotubes as drug delivery molecules to enhance the treatment of hematological malignancies

Carolyne R. Falank1,2,3, Aaron W. Tasset4, Sophie Harris1,2,3, Mariah Farrell1,2,3, Milos Marinkovic4, Michaela R. Reagan1,2,3

1Maine Medical Center Research Institute, Scarborough, ME 04074. 2University of Maine, Orono, Maine. 3Tufts University, Boston Massachusetts. 4BioPact Ventures, LLC, Austin, TX 78736.

Burkitt’s lymphoma is an aggressive B-cell derived non-Hodgkin lymphoma. Doxorubicin (Dox) constitutes a common therapy, but features numerous side effects, including significant weight and hair loss, myelotoxicity, cardiovascular damage and treatment-related leukemia. Tumor-specific delivery holds great promise for mitigating adverse side effects while maintaining therapeutic effectiveness of Dox. Carbon nanotubes (CNTs) are highly-prospective drug delivery vehicles due to their unique architecture, high drug-loading surface area and tunable chemistry. Unfortunately, in vivo toxicology, elicited by poor physiological solubility/clearance and high residual contaminants, has prohibited clinical translation of CNTs. XACT™ is a novel drug delivery technology which overcomes these obstacles by utilizing purified, discrete CNTs (dCNTs), bio-compatibilized and highly stable in vivo.

To evaluate long-term stability of dCNTs in physiological conditions, zeta potential (-40 to -50 mV) analysis were performed in ionic, high-serum solutions. No toxicity of dCNTs was observed across multiple cell types in vitro or in murine in vivo models, establishing a high MTD of 70 mg/kg for IV administration. Biodistribution studies (34 days) were conducted in female BALB/C mice using radioisotope-labeled dCNTs. Approximately 60% of injected dCNTs were retained in bone, while the remaining fraction demonstrated high-tolerability and clearance from various organs. Critically, in vitro drug delivery studies showed that dCNT endocytosis is non-cytotoxic and unloaded cargos retain functionality.

We evaluated the considerable potential of dCNTs for bone-specific drug delivery in a murine Raji-Burkitt’s lymphoma model. Whole body bioluminescence imaging revealed that, similarly to those treated with free Dox, groups receiving the Dox-loaded dCNTs showed greatly reduced tumor burden compared to untreated. However, the group receiving Dox-loaded dCNTs also demonstrated increased survival compared to free Dox. Furthermore, typical murine indications of Dox toxicity, characterized by rapid weight loss or drug-related mortality, were not observed in groups receiving Dox-loaded CNTs indicating dCNT’s ability to mitigate negative side effects while retaining efficacy.

In summary, XACT™ dCNTs are a highly-stable, nontoxic and versatile vehicle, featuring a promising capability for targeted delivery to bone tissue. This novel technology provides considerable clinical potential as a therapeutic delivery mechanism for diseases of bone and bone marrow, but also for osteoregenerative applications.

Presentations

Learn more about the most recent BPCT presentations with the links below.

LocationConferenceDate
London, UKAdvanced Therapies & Regenerative Medicine Congress May, 2019
Boston, USA 7th Immuno-oncology SummitAugust, 2019
Amsterdam, NLCell Therapy Manufacturing & Gene Therapy CongressDecember, 2019