Targeted delivery of platinum-based anticancer complexes

Abstract

The most widely used anticancer drugs are platinum-based. Their efficacy might be improved by carriers which can transport large numbers of Pt centres, shield the drug from premature activation, and/or deliver Pt specifically to cancer cells using vectors which recognise specific targets. We describe recent progress using functionalized carbon nanotubes (CNTs) and nanorods, hollow Prussian blue (HPB), magnetic iron oxide and gold nanoparticles, liposomes, nanogels and polymers, as well as active targeting by conjugation to biodegradable proteins and peptides (e.g. EGF, heparin, herceptin, somatostatin and TAT). Spatially targeted activation of Pt(IV) prodrugs using light is also a promising approach. Interestingly, use of these new delivery and targeting systems for platinum drugs can lead to species with unusual reactivity which can kill cancer cells by new mechanisms.

From Traditional Drug Design to Catalytic Metallodrugs: A Brief History of the Use of Metals in Medicine

“…The focus of this review, following a historical perspective, is on actual, or potential, metal-based drugs that promote therapeutic activity through direct metal-centered binding or reactivity. Other approaches that employ outer sphere contacts of coordination complexes or reactivity toward ill-defined cellular targets are not included for reasons of space limitations, although interested readers are directed to other informative reviews and articles [13][14][15][16][17][18][19][20].…”

Prodrug-based nano-drug delivery system for co-encapsulate paclitaxel and carboplatin for lung cancer treatment

“…The difficulty in co-encapsulating hydrophilic and hydrophobic drugs leads to a major obstacle on the possible therapy combinations. Chemical modifications (prodrug) and polymeric NPs, prodrug-based nano-drug delivery system (P-N-DDS), have been published mostly as a platform to overcome this difficulty (Shiah et al, 2001;Kolishetti et al, 2010;Hu & Zhang, 2012;Xiao et al, 2012;Butler & Sadler, 2013;Oberoi et al, 2013). PLGA-PEG is one of the most common hydrophobic biodegradable polymers for NPs and prodrug nano-DDS (Kolishetti et al, 2010;Dhar et al, 2011;Xu et al, 2013;Zhang et al, 2014).…”

DNA-based aptamer fails as a simultaneous cancer targeting agent and drug delivery vehicle for a phenanthroline-based platinum(II) complex

“…Whilst effective, the six drugs currently on the market display poor selectivity for cancers compared with other rapidly dividing cells within the human body. As a result there has been enormous interest in the development of delivery vehicles for platinum drugs, which are able to either passively or actively target solid tumours, whilst sparing normal tissue from damage [3][4][5].…”