Bacterially Derived 400 nm Particles for Encapsulation and Cancer Cell Targeting of Chemotherapeutics

Abstract

Systemic administration of chemotherapeutic agents results in indiscriminate drug distribution and severe toxicity. Here we report a technology potentially overcoming these shortcomings through encapsulation and cancer cell-specific targeting of chemotherapeutics in bacterially derived 400 nm minicells. We discovered that minicells can be packaged with therapeutically significant concentrations of chemotherapeutics of differing charge, hydrophobicity, and solubility. Targeting of minicells via bispecific antibodies to receptors on cancer cell membranes results in endocytosis, intracellular degradation, and drug release. This affects highly significant tumor growth inhibition and regression in mouse xenografts and case studies of lymphoma in dogs despite administration of minute amounts of drug and antibody; a factor critical for limiting systemic toxicity that should allow the use of complex regimens of combination chemotherapy.

Image-guided and passively tumour-targeted polymeric nanomedicines for radiochemotherapy

“…Over the years, a variety of different drug targeting systems have been developed, ranging in nature from simple polymers (Duncan, 2006) and liposomes (Torchilin, 2005), to stimuli-sensitive polymeric micelles (Rapoport et al, 2007), bacterially derived Minicells (MacDiarmid et al, 2007), and temporally targeted Nanocells (Sengupta et al, 2005). Thus far, however, not very many have managed to reach the final stages of clinical evaluation, and only about a handful have been approved by the responsible regulatory authorities.…”

miRNAs as Biomarkers and Therapeutic Targets in Non-Small Cell Lung Cancer: Current Perspectives

“…Recently, as an alternative to the liposomal or nanoparticle-based methods of miRNA delivery, the EDV™ nanocells (EDVs) have been employed [199,200]. This delivery system developed by EnGeneIC Ltd (Sydney, Australia) comprises nonviable minicells 400 ± 20 nm in diameter, produced by de-repressing polar sites of cell division in bacteria [201]. Once loaded, EDVs are coated with a bispecific antibody (BsAB), where one arm is available for binding to a receptor expressed on the surface of cancer cells.…”

miRNA-182 and the regulation of the glioblastoma phenotype - toward miRNA-based precision therapeutics

“…Miravirsen is a miR-122 antagonist used for the treatment of Hepatitis C virus infection 52 and TargoMiR, a miR-16 mimic, has been used in patients with recurrent malignant pleural mesothelioma (MPM) and advanced non-small cell lung cancer (NSCLC), delivered intavenously with epidermal growth factor receptor (EGFR)-targeted minicells. [53][54][55] A variety of nanoparticle-based delivery methods have been developed for the robust and safe delivery of siRNA and miRNA payloads, including inorganic, polymer or lipid-based nanoparticles. 2,56 A silica-based nanoparticle conjugated with a disialoganglioside GD2 antibody as targeting moiety was used to express miR-34a in neuroblastoma, which reduced tumor growth and vascularization by decreasing the levels of N-myc and increasing tissue inhibitor of metallopeptidase 2 (TIMP2).…”