Nanotherapy appears effective against MM

Lab mice

Photo by Aaron Logan

A nanoparticle-based therapy can effectively fight multiple myeloma (MM), according to preclinical research published in Molecular Cancer Therapy.

The nanoparticles protected their therapeutic cargo from degradation in the bloodstream and enhanced drug delivery into MM cells, thereby improving survival in mouse models of MM.

The nanoparticles carried an Sn 2 lipase-labile prodrug inhibitor of MYC-MAX dimerization (MI1-PD).

Researchers designed this prodrug for use in MM because MM pathogenesis is driven by the MYC oncoprotein, its dimerization with MAX, and the binding of this heterodimer to E-Boxes in the vicinity of target genes.

Previous research has shown that MYC inhibitors are extremely potent in vitro, but, when injected into the blood, they degrade immediately. The current study is the first to show that a MYC inhibitor can be effective in animals with cancer, as long as the drug has a vehicle to protect and deliver it into cancer cells.

“The nanoparticles serve as vehicles that protect the drug from the harsh environment of the blood,” said study author Gregory M. Lanza, MD, PhD, of the Washington University School of Medicine in St Louis, Missouri.

“In this case, the drug is modified into a prodrug and actually locked into the outer membrane of the particle.”

The nanoparticles are designed to carry targeting molecules that home in on and bind to MM cells that carry the complementary receptor. When a nanoparticle binds to an MM cell, their membranes fuse together, transferring MI1-PD to the malignant cell. When safely inside, MI1-PD is enzymatically freed to do its job, blocking MYC from activation.

In theory, noncancerous cells are unlikely to be adversely affected by MYC inhibition because healthy cells shouldn’t have highly activated MYC proteins to begin with, according to the researchers.

The team injected 2 sizes of MI1-PD-containing nanoparticles into mice with MM and found that the nanoparticles increased the animals’ median survival.

The median survival was 46 days for mice that received MI1-PD-containing, 200-nm nanoparticles and 28 days for mice that received control, 200-nm nanoparticles (P<0.05). For mice that received 20 nm nanoparticles, the median survival was 52 days and 29 days, respectively (P=0.001).

The researchers also pointed out that neither MI1 nor MI1-PD conferred a survival benefit for the mice when injected without nanoparticle protection.

“We’re excited about our results because there was no guarantee the nanotherapy would increase survival,” said study author Michael H. Tomasson, MD, of the Washington University School of Medicine.

“We injected the nanoparticles intravenously, and they found the tumors throughout the body, whether they were in the bone marrow, the spleen, or elsewhere.”

Drs Tomasson and Lanza said this technology is still years away from clinical trials, but they are optimistic about its future potential and are eager to begin that work.

Lab mice

Photo by Aaron Logan

A nanoparticle-based therapy can effectively fight multiple myeloma (MM), according to preclinical research published in Molecular Cancer Therapy.

The nanoparticles protected their therapeutic cargo from degradation in the bloodstream and enhanced drug delivery into MM cells, thereby improving survival in mouse models of MM.

The nanoparticles carried an Sn 2 lipase-labile prodrug inhibitor of MYC-MAX dimerization (MI1-PD).

Researchers designed this prodrug for use in MM because MM pathogenesis is driven by the MYC oncoprotein, its dimerization with MAX, and the binding of this heterodimer to E-Boxes in the vicinity of target genes.

Previous research has shown that MYC inhibitors are extremely potent in vitro, but, when injected into the blood, they degrade immediately. The current study is the first to show that a MYC inhibitor can be effective in animals with cancer, as long as the drug has a vehicle to protect and deliver it into cancer cells.

“The nanoparticles serve as vehicles that protect the drug from the harsh environment of the blood,” said study author Gregory M. Lanza, MD, PhD, of the Washington University School of Medicine in St Louis, Missouri.

“In this case, the drug is modified into a prodrug and actually locked into the outer membrane of the particle.”

The nanoparticles are designed to carry targeting molecules that home in on and bind to MM cells that carry the complementary receptor. When a nanoparticle binds to an MM cell, their membranes fuse together, transferring MI1-PD to the malignant cell. When safely inside, MI1-PD is enzymatically freed to do its job, blocking MYC from activation.

In theory, noncancerous cells are unlikely to be adversely affected by MYC inhibition because healthy cells shouldn’t have highly activated MYC proteins to begin with, according to the researchers.

The team injected 2 sizes of MI1-PD-containing nanoparticles into mice with MM and found that the nanoparticles increased the animals’ median survival.

The median survival was 46 days for mice that received MI1-PD-containing, 200-nm nanoparticles and 28 days for mice that received control, 200-nm nanoparticles (P<0.05). For mice that received 20 nm nanoparticles, the median survival was 52 days and 29 days, respectively (P=0.001).

The researchers also pointed out that neither MI1 nor MI1-PD conferred a survival benefit for the mice when injected without nanoparticle protection.

“We’re excited about our results because there was no guarantee the nanotherapy would increase survival,” said study author Michael H. Tomasson, MD, of the Washington University School of Medicine.

“We injected the nanoparticles intravenously, and they found the tumors throughout the body, whether they were in the bone marrow, the spleen, or elsewhere.”

Drs Tomasson and Lanza said this technology is still years away from clinical trials, but they are optimistic about its future potential and are eager to begin that work.

Lab mice

Photo by Aaron Logan

A nanoparticle-based therapy can effectively fight multiple myeloma (MM), according to preclinical research published in Molecular Cancer Therapy.

The nanoparticles protected their therapeutic cargo from degradation in the bloodstream and enhanced drug delivery into MM cells, thereby improving survival in mouse models of MM.

The nanoparticles carried an Sn 2 lipase-labile prodrug inhibitor of MYC-MAX dimerization (MI1-PD).

Researchers designed this prodrug for use in MM because MM pathogenesis is driven by the MYC oncoprotein, its dimerization with MAX, and the binding of this heterodimer to E-Boxes in the vicinity of target genes.

Previous research has shown that MYC inhibitors are extremely potent in vitro, but, when injected into the blood, they degrade immediately. The current study is the first to show that a MYC inhibitor can be effective in animals with cancer, as long as the drug has a vehicle to protect and deliver it into cancer cells.

“The nanoparticles serve as vehicles that protect the drug from the harsh environment of the blood,” said study author Gregory M. Lanza, MD, PhD, of the Washington University School of Medicine in St Louis, Missouri.

“In this case, the drug is modified into a prodrug and actually locked into the outer membrane of the particle.”

The nanoparticles are designed to carry targeting molecules that home in on and bind to MM cells that carry the complementary receptor. When a nanoparticle binds to an MM cell, their membranes fuse together, transferring MI1-PD to the malignant cell. When safely inside, MI1-PD is enzymatically freed to do its job, blocking MYC from activation.

In theory, noncancerous cells are unlikely to be adversely affected by MYC inhibition because healthy cells shouldn’t have highly activated MYC proteins to begin with, according to the researchers.

The team injected 2 sizes of MI1-PD-containing nanoparticles into mice with MM and found that the nanoparticles increased the animals’ median survival.

The median survival was 46 days for mice that received MI1-PD-containing, 200-nm nanoparticles and 28 days for mice that received control, 200-nm nanoparticles (P<0.05). For mice that received 20 nm nanoparticles, the median survival was 52 days and 29 days, respectively (P=0.001).

The researchers also pointed out that neither MI1 nor MI1-PD conferred a survival benefit for the mice when injected without nanoparticle protection.

“We’re excited about our results because there was no guarantee the nanotherapy would increase survival,” said study author Michael H. Tomasson, MD, of the Washington University School of Medicine.

“We injected the nanoparticles intravenously, and they found the tumors throughout the body, whether they were in the bone marrow, the spleen, or elsewhere.”

Drs Tomasson and Lanza said this technology is still years away from clinical trials, but they are optimistic about its future potential and are eager to begin that work.