Nanoparticle Therapy Targets Tumor-Associated Immunosuppressive Cells

Nanoparticles loaded with siRNA (small interfering RNA) were able to destroy ovarian tumors by converting immunosuppressive dendritic cells associated with the tumors into potent immunostimulatory cells that both generated antitumor antibodies and directly attacked the cancer cells.

Investigators at Dartmouth Medical School (Hanover, NH, USA) observed that nanoparticles made from linear polyethylenimine (PEI) and siRNA (siRNA-PEI nanoparticles) were selectively engulfed by tumor-associated immune dendritic cells. In contrast, the cancer cells making up the tumor failed to incorporate the nanoparticles.

Fortunately, the siRNA-PEI nanoparticles caused a dramatic change in the behavior pattern of the tumor-associated dendritic cells. Uptake of nanoparticles transformed these dendritic cells from immunosuppressive cells to efficient antigen-presenting cells that activated tumor-reactive lymphocytes and exerted direct tumoricidal activity. This transformation appeared to be linked to the activation of several different Toll-like receptors.

Nanoparticles loaded with siRNA that inhibited specific immunosuppressive genes gave superior therapeutic results in mice with ovarian cancer than did nanoparticles loaded with nonspecific siRNA.

"We have modulated elements of the tumor microenvironment that are not cancer cells, reversing their role as accomplices in tumor growth to attackers that boost responses against the tumor," said senior author Dr. Jose Conejo-Garcia, assistant professor of microbiology at Dartmouth Medical School. "The cooperating cells hit by the particles return to fighters that immediately kill tumor cells."

"This could be part of a ‘multimodal approach,' against ovarian cancer," said Dr. Conejo-Garcia. "The prevailing treatment is surgical debulking, followed by chemotherapy. Our findings could complement those because they target not the tumor cells themselves, but different cells present around the tumor."

Related Links
Dartmouth Medical School