Monoclonal antibody‐targeted polymeric nanoparticles for cancer therapy – future prospects

Abstract

Although combination therapy for cancer utilising monoclonal antibodies in conjunction with chemotherapeutic drugs has resulted in increases in 5 year survivals, there nevertheless remains significant morbidity and mortality associated with systemic delivery of cytotoxic drugs. The advent of living radical polymerisation has resulted in complex and elegant nanoparticle structures that can be engineered to passively target a drug payload for cancer treatment. This presents a therapeutic modality whereby biodistribution and consequently systemic toxicity can be reduced, while focusing drug delivery to the tumour site. Nanoparticle delivery can be enhanced by attachment of a targeting monoclonal antibody fragment to facilitate tumour cell uptake through endocytosis, and so increase therapeutic efficacy. In this way, monoclonal antibodies can be supercharged by carrying a payload consisting of a cocktail of conventional chemotherapeutic drugs and siRNA. This review will focus on antibody-targeted polymeric nanoparticles to cancer cells, and methods and technologies for synthesising such antibody-targeted nanoparticles. The review is confined to polymeric-based nanoparticles as these offer some advantages over liposomal nanoparticles and may circumvent some of the pitfalls in nanomedicine. Development of these antibody based polymeric nanoparticles and future directions for therapy are highlighted in this review.

Ligand-based targeted therapy: a novel strategy for hepatocellular carcinoma

“…136,137 For instance, iodine ( 131 I) metuximab injection (Licartin ® ), a 131 I-labeled HAb18G/CD147-specific monoclonal antibody (mAb) F(ab') 2 fragment, has been approved for the treatment of primary HCC by the China State Food and Drug Administration. 138 The HAb18G/ CD147, an antigen for being homologous to CD147, is highly expressed on HCC cells and tissues and can bind to the bivalent fragment HAb18 F(ab') 2 of HAb18 mAb with high affinity.…”

Advances in Drug Delivery

“…4 Although liposomal-based nanoparticles have been approved for therapy, polymeric nanoparticles are more versatile and offer some advantages over liposomes. Antibodies that have been selected for targeting and the various strategies for creating polymeric nanoparticles are discussed along with recent strategies for preparing biopolymer conjugates.…”

Development of anti-PEG bispecific antibodies for targeting PEGylated nanoparticles to tumour cells

“…Nanoparticles currently in development include dendrimers, liposomes, polymeric particles, micelles, protein cages, ceramic particles, metallic nanoparticles and functionalized carbon nanotubes (Byrne 2008). Untargeted nanoparticles, including the FDA, approved Doxil, accumulate within tumours due to the enhanced permeability and retention (EPR) effect at tumour sites, and may release their active compounds due to a time delay mechanism, degradation of the nanoparticle or linker following internalization (Firer 2013, Goodall et al 2014, Sanna et al 2014. These same principles also allow for the use of labelled nanoparticles as a means to conduct cancer imaging, this allows for the collection of important information regarding the staging of cancer.…”