Dr Roger Liang

Aim: To develop matrix metalloproteinase-responsive gelatin-albumin hybrid nanoparticles encapsulating a selective tropomyosin receptor kinase A (TrkA) inhibitor GNF-5837 (Gel-Alb-GNF HNPs) and to demonstrate their anticancer effects in breast cancer. Methods: Gel-Alb-GNF HNPs were prepared using a pH-controlled complexation process from cationic gelatin, dextran sulfate and albumin-bound GNF-5837. The anticancer activities of Gel-Alb-GNF HNPs were tested in a panel of subtype-specific breast cancer cell lines. Results: Gel-Alb-GNF HNPs (~130 nm) displayed excellent stability and matrix metalloproteinase-triggered drug release. Compared with GNF-5837 alone, Gel-Alb-GNF HNPs not only significantly enhanced the antiproliferative and anti-invasive effects but also restored the apoptosis of cancer cells. Conclusion: Gel-Alb-GNF HNPs may be adaptable for stand-alone therapies or used in combination with traditional chemotherapies for breast cancer treatment.

The use of nanotechnology has great potentials to revolutionize the future cancer diagnosis and therapy. In this context, various nanoparticles (NPs) have been developed for targeted delivery of diagnostic/therapeutic agents to the tumor sites, which thus result in greater efficacy and much less side effects. The targeting property of NPs is often achieved by functionalizing their surface with tumor-specific ligands, such as antibodies, peptides, small molecules and oligonucleotides. In this review, we will discuss recent progress in the multifunctional design of antibody-targeted NPs with a special focus on liposomal, polymeric and protein-based delivery systems.

Albendazole (ABZ), a well-established antiparasitic drug, has been shown to suppress tumor growth in a number of preclinical models of cancer. However, the low solubility of ABZ limits its use as a systemic anticancer agent. To enable systemic administration, we have formulated ABZ into albumin nanoparticles with a size range of 200-300 nm, which were cross-linked with glutaraldehyde to stabilize the nanoparticles and to introduce pH-responsive features. Drug release studies demonstrated that about 20% of ABZ was released at neutral pH within a week in comparison to 70% at slightly acidic condition (pH 5). Cellular uptake studies using ovarian cancer cells indicated that nanoparticles were internalized efficiently within 1 h of incubation. Further, cell proliferation results demonstrated that albumin nanoparticles alone showed no cytotoxicity to both normal and cancer cells. In contrast, the drug-loaded nanoparticles exhibited cellular toxicity and high killing efficacy to cancer cells compared to normal cells. Collectively, our results suggest that these albumin nanoparticles may hold great potentials as ABZ carriers for cancer therapy.