Abstract

Engineering of Antibody Conjugated Drug Loaded Nanoparticle for Targeted Drug Delivery

Ajay Kumar Gupta, Director & Head, Confederation of Indian Industry

The therapeutic potential of targeting antibodies can be enhanced by conjugating them to therapeutic drugs. This combination merges the benefits of highly potent drugs with selective binders of specific tumor antigens. Antibody-drug conjugates offer the promise of delivering more powerful tumor-killing activity while resulting in diminished side effects for cancer patients. However, such immunoconjugates and the methods to produce them adversely affect the pharmacological action of the drug, as well as its in vivo fate, and the conjugation methods allow few drug molecules to be attached to the antibody. Nanoparticulate drug delivery systems with bound tumor-selective ligands confer greater selectivity and could potentially carry more drug compared with drug molecules directly conjugated to an antibody. Multifunctional nanoparticles harbouring various functions including targeting, imaging, therapy have been intensively studied aiming to overcome limitations associated with conventional cancer diagnosis and therapy. At present, several targeted delivery systems are under clinical trials, such as transferrin receptor targeted cytotoxic platinum-based oxaliplatin in a liposome (MBP-426), transferrin receptor targeted cyclodextrin-containing nanoparticles with siRNA payload (CALAA-01), or prostate-specific membrane antigen (PSMA) targeted polymeric nanoparticles containing docetaxel (BIND-014). In this review, various selective targeting strategies using nanoparticles for achieving effective cancer detection and treatment would be discussed. Various targeting moieties which may be used as 'escort' molecules to specific tumor tissues including peptides and antibodies etc would be discussed. In addition, different methods of conjugating the functional moieties to nanoparticles and strat