Detoxifying antitumoral drugs via nanoconjugation: the case of gold nanoparticles and cisplatin.
Nanoparticles (NPs) have emerged as a potential tool to improve cancer treatment. Among the proposed uses in imaging and therapy, their use as a drug delivery scaffold has been extensively highlighted. However, there are still some controversial points which need a deeper understanding before clinical application can occur. Here the use of gold nanoparticles (AuNPs) to detoxify the antitumoral agent cisplatin, linked to a nanoparticle via a pH-sensitive coordination bond for endosomal release, is presented. The NP conjugate design has important effects on pharmacokinetics, conjugate evolution and biodistribution and results in an absence of observed toxicity. Besides, AuNPs present unique opportunities as drug delivery scaffolds due to their size and surface tunability. Here we show that cisplatin-induced toxicity is clearly reduced without affecting the therapeutic benefits in mice models. The NPs not only act as carriers, but also protect the drug from deactivation by plasma proteins until conjugates are internalized in cells and cisplatin is released. Additionally, the possibility to track the drug (Pt) and vehicle (Au) separately as a function of organ and time enables a better understanding of how nanocarriers are processed by the organism.
Catalan Institute of Nanotechnology (ICN), Universitat Autònoma de Barcelona (UAB), Bellaterra, Barcelona, Spain.
Joan
J
Comenge
Carmen
C
Sotelo
Francisco
F
Romero
Oscar
O
Gallego
Agustí
A
Barnadas
Tomás García-Caballero
TG
Parada
Fernando
F
Domínguez
Víctor F
VF
Puntes
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry; D004705:Endocytosis / Q000187:drug effects; D006046:Gold / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008658:Inactivation, Metabolic; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000633:toxicity / Q000648:ultrastructure; D051379:Mice; D036103:Nanotechnology / Q000379:methods*; D009929:Organ Size / Q000187:drug effects; D013997:Time Factors; D014018:Tissue Distribution / Q000187:drug effects; D014481:United States; D014486:United States Food and Drug Administration
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D004337:Drug Carriers; D006046:Gold; D002945:Cisplatin