Targeted Delivery of siRNA Lipoplexes to Cancer Cells Using Macrophage Transient Horizontal Gene Transfer

Abstract

Delivery of nucleic acids into solid tumor environments remains a pressing challenge. This study examines the ability of macrophages to horizontally transfer small interfering RNA (siRNA) lipoplexes to cancer cells. Macrophages are a natural candidate for a drug carrier because of their ability to accumulate at high densities into many cancer types, including, breast, prostate, brain, and colon cancer. Here, it is demonstrated that macrophages can horizontally transfer siRNA to cancer cells during in vitro coculture. The amount of transfer can be dosed depending on the amount of siRNA loaded and total number of macrophages delivered. Macrophages loaded with calcium integrin binding protein‐1 (CIB1)‐siRNA result in decreased tumorsphere growth and decreased mRNA expression of CIB1 and KI67 in MDA‐MB‐468 human breast cancer cells. Adoptive transfer of macrophages transfected with CIB1‐siRNA localizes to the orthotopic MDA‐MB‐468 tumor. Furthermore, it is reported that macrophage activation can modulate this transfer process as well as intracellular trafficking protein Rab27a. As macrophages are heavily involved in tumor progression, understanding how to use macrophages for drug delivery can substantially benefit the treatment of tumors.

Genetically modified macrophages accomplish targeted gene delivery to the inflamed brain in transgenic Parkin Q311X(A) mice: importance of administration routes

“…Thus, pre-transfected macrophages serve as “donors” that pass or “horizontally transfer” the gene to acceptor cells. In this respect, we demonstrated recently that transfected macrophages can pass p DNA to muscle cells 55 , and siRNA to cancer cells 56 , causing significant antitumor effects. In addition, GDNF-BMM can also deliver the overexpressed neurotrophic factor.…”

Recent Advances in Macrophage-Mediated Drug Delivery Systems

“… 20 Nanoporous silicon particles were later encapsulated with purified mononuclear macrophage membranes, resulting in materials with macrophage-like functions. 21 Based on these encouraging findings, the application of macrophages as carriers for the delivery of drugs with different properties has been significantly expanded in order to study and treat various conditions such as cancer, 22 inflammation, 23 and HIV infection 24 ( Table 1 ).…”

Following the Fate of Dye-Containing Liposomes In Vitro

“…Furthermore, side scattering was recorded to confirm the granularity of macrophages (Ch6, 762/35). The liposome uptake was imaged in green fluorescence (Ch02, 528/65 nm) after 4, 6, 12, 18 and 24 h. Untreated live and dead cells were also imaged, as negative and positive controls, respectively, to adjust for auto-fluorescence and validate the gating tree [43].…”