Synergistic photo-release of drugs by non-linear excitation
- PDF / 6,963,201 Bytes
- 9 Pages / 612 x 792 pts (letter) Page_size
- 41 Downloads / 155 Views
Synergistic photo-release of drugs by non-linear excitation Valerio Voliani*,1,2 Giovanni Signore,2 Orazio Vittorio,3 Paolo Faraci,1 Stefano Luin,1 Julia Peréz-Prieto,4 and Fabio Beltram1 1
NEST- Scuola Normale Superiore and Istituto Nanoscienze-CNR, Piazza San Silvestro 12, 56127 Pisa (Italy). 2 Center for Nanotechnology Innovation @NEST, Istituto Italiano di Tecnologia, Piazza San Silvestro 12, 56127 Pisa (Italy). 3 Children's Cancer Institute Australia, Lowy Cancer Research Centre and Australian Centre for Nanomedicine, University of New South Wales, Randwick, New South Wales (Australia). 4 Universidad de Valencia, Instituto de Ciencia Molecular, ICMol, Catedrático Jose Beltrán, 2,46980 Paterna, Valencia (Spain) E-mail: [email protected] ABSTRACT Nanomaterials engineered in novel multi-modular systems in which every component works in a synergistic way with others could potentially lead to a completely new type of tools for nanomedicine. The development of nanostructures able to release drugs directly within the target after a stimulus can drastically improve the therapeutics efficiency by reducing side effects. Gold nanoparticles offer one of the most suitable platforms for the development of modular nano-devices. On the one hand, their surface properties enable effective coating by peptides containing at least one cysteine, thus yielding stable and non-cytotoxic systems. On the other, their intriguing photophysics, characterized by the surface plasmon resonance, can be exploited for novel excitation schemes. Doxorubicin is a widely used, but toxic, cancer chemotherapeutic agent. In order to localize its therapeutic action while minimizing its side effects, doxorubicin was covalently conjugated to 30 nm peptide-encapsulated gold nanospheres by click-chemistry and then it was photo-released in a controlled fashion through the cleavage of the 1,2,3-triazolic ring by a multiphoton process using 561 nm irradiation at µW power. Selective apoptosis of human osteosarcoma (U2OS) cells was observed only in the irradiated 100x100 micron area in less than six minutes after the stimulus. Notably, the apoptotic effect of doxorubicin was completely inhibited for at least eight hours until its release “on demand” was externally light-triggered. INTRODUCTION Doxorubicin (D) is a Food and Drug Administration (FDA)-approved drug commonly used in the treatment of a wide range of cancers including hematological malignancies, many types of carcinoma, and soft-tissue sarcomas (Peer, Karp, & Hong, 2007; You, Zhang, Zhang, & Zhong, 2012). Despite its broad use in cancer chemotherapy, D presents some considerable drawbacks, such as cardio-toxicity and short life-time in the body. In order to maximize its therapeutic effects while minimizing side effects, a drug-delivery system able to promote controlled drug release in terms of dose, location, and time, is desirable (E. C. E. Dreaden,
Alkilany, Huang, Murphy, & El-Sayed, 2011; Llevot & Astruc, 2012; Vittorio et al., 2014; Voliani, Ricci, Signore, et al., 2012). Gold nanoparticles (AuN
Data Loading...
