Theranostic Nanocages for Imaging and Photothermal Therapy of Prostate Cancer Cells by Active Targeting of Neuropeptide-Y Receptor.
Gold nanocages (AuNCs) have been shown to be a useful tool for harnessing imaging and hyperthermia therapy of cancer, thanks to their unique optical properties, low toxicity, and facile surface functionalization. Herein, we use AuNCs for selective targeting of prostate cancer cells (PC3) via specific interaction between neuropeptide Y (NPY) receptor and three different NPY analogs conjugated to AuNCs. Localized surface plasmon resonance band of the nanoconjugates was set around 800 nm, which is appropriate for in vivo applications. Long-term stability of nanoconjugates in different media was confirmed by UV-vis and DLS studies. Active NPY receptor targeting was observed by confocal microscopy showing time-dependent AuNCs cellular uptake. Activation of ERK1/2 pathway was evaluated by Western blot to confirm the receptor-mediated specific interaction with PC3. Cellular uptake kinetics were compared as a function of peptide structure. Cytotoxicity of nanoconjugates was evaluated by MTS and Annexin V assays, confirming their safety within the concentration range explored. Hyperthermia studies were carried out irradiating the cells, previously incubated with AuNCs, with a pulsed laser at 800 nm wavelength, showing a heating enhancement ranging from 6 to 35 °C above the culture temperature dependent on the irradiation power (between 1.6 and 12.7 W/cm2). Only cells treated with AuNCs underwent morphological alterations in the cytoskeleton structure upon laser irradiation, leading to membrane blebbing and loss of microvilli associated with cell migration. This effect is promising in view of possible inhibition of proliferation and invasion of cancer cells. In summary, our Au-peptide NCs proved to be an efficient theranostic nanosystem for targeted detection and activatable killing of prostate cancer cells.
Svetlana
S
Avvakumova
Elisabetta
E
Galbiati
Laura
L
Sironi
Università degli Studi di Milano , Dipartimento di Scienze Farmaceutiche, via Mangiagalli 25, 20133, Milano, Italy.
Silvia A
SA
Locarno
Università degli Studi di Milano , Dipartimento di Scienze Farmaceutiche, via Mangiagalli 25, 20133, Milano, Italy.
Luca
L
Gambini
Università degli Studi di Milano , Dipartimento di Scienze Farmacologiche e Biomolecolari, via Balzaretti 9, 20133, Milano, Italy.
Chiara
C
Macchi
Laura
L
Pandolfi
Università degli Studi di Milano , Dipartimento di Scienze Farmacologiche e Biomolecolari, via Balzaretti 9, 20133, Milano, Italy.
Massimiliano
M
Ruscica
Università degli Studi di Milano , Dipartimento di Scienze Farmacologiche e Biomolecolari, via Balzaretti 9, 20133, Milano, Italy.
Paolo
P
Magni
Maddalena
M
Collini
Miriam
M
Colombo
Surgery Department, Breast Unit, ICS Maugeri S.p.A. SB , via S. Maugeri 10, 27100, Pavia, Italy.|Department of Biomedical and Clinical Sciences L. Sacco, University of Milan , Via. G.B. Grassi 74, 20157, Milano, Italy.
Fabio
F
Corsi
Giuseppe
G
Chirico
Università degli Studi di Milano , Dipartimento di Scienze Farmaceutiche, via Mangiagalli 25, 20133, Milano, Italy.
Sergio
S
Romeo
Davide
D
Prosperi
D045744:Cell Line, Tumor; D015195:Drug Design; D006046:Gold; D006801:Humans; D007834:Lasers; D008297:Male; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D058990:Molecular Targeted Therapy / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000628:therapy*; D017476:Receptors, Neuropeptide Y / Q000378:metabolism; D000068936:Theranostic Nanomedicine / Q000379:methods*; D013817:Thermography / Q000379:methods
D010455:Peptides; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; D006046:Gold