Theranostic Nanocages for Imaging and Photothermal Therapy of Prostate Cancer Cells by Active Targeting of Neuropeptide-Y Receptor

Abstract

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 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 to 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.

Does conjugation strategy matter? Cetuximab-conjugated gold nanocages for targeting triple-negative breast cancer cells

“…9 In addition, AuNCs could be exploited for the conversion of irradiated energy into heat upon light absorption in the NIR region, thereby behaving like nanomediators in photothermal therapy. 8 CTX was chosen as the biorecognition molecule because of its prevalent use for therapeutic and diagnostic targeting processes for ErbB1 receptors in several tumor malignancies, including breast cancer. 38 The rst part of this study was dedicated to the optimization of the composition of AuNCs ligand shell and development of an appropriate synthesis protocol to obtain stable nanoconjugates.…”

“…Although the synthesis of such NPs is not straightforward since it requires multiple steps of synthesis and purication, we have already shown that AuNCs are a competitive tool for imaging because of their unique optical properties, which avoids the use of uorescent dyes, and therefore, problems related to uorescence bleaching and artifacts in biologic readouts related to the presence of organic dyes. 8,9 Because of their strong absorption in the NIR region, AuNCs have become an alternative tool for imaging. CTX mAbs were used as the model molecule for conjugation to AuNCs, one of the most relevant mAbs in cancer therapeutics.…”

Targeting of peptide‐binding receptors on cancer cells with peptide‐drug conjugates

“…However, all of these approaches use nanoparticle‐based platforms, decorated with hY 1 R‐binding peptides as targeting units. [ 126–129 ]…”

A Gold Nanocage/Cluster Hybrid Structure for Whole‐Body Multispectral Optoacoustic Tomography Imaging, EGFR Inhibitor Delivery, and Photothermal Therapy

“…Gold nanocages (AuNCs) are a class of hollow nanostructures with porous walls. Since their debut over a decade ago, they have gained enormous attention for their potential to achieve various biomedical applications such as bioimaging, and drug delivery and therapy owing to their bioinert nature, tunable localized surface plasmon resonance (LSPR) peaks, and high photothermal conversion efficiency . In particular, with hollow interiors and porous walls, AuNCs can be readily loaded with various drugs in their interiors with high loading efficacy, making the them ideal for drug delivery in therapeutic applications.…”