New Targeted Gold Nanorods for the Treatment of Glioblastoma by Photodynamic Therapy

Abstract

This study describes the employment of gold nanorods (AuNRs), known for their good reputation in hyperthermia-based cancer therapy, in a hybrid combination of photosensitizers (PS) and peptides (PP). We report here, the design and the synthesis of this nanosystem and its application as a vehicle for the selective drug delivery and the efficient photodynamic therapy (PDT). AuNRs were functionalized by polyethylene glycol, phototoxic pyropheophorbide-a (Pyro) PS, and a "KDKPPR" peptide moiety to target neuropilin-1 receptor (NRP-1). The physicochemical characteristics of AuNRs, the synthesized peptide and the intermediate PP-PS conjugates were investigated. The photophysical properties of the hybrid AuNRs revealed that upon conjugation, the AuNRs acquired the characteristic properties of Pyro concerning the extension of the absorption profile and the capability to fluoresce (Φ f = 0.3) and emit singlet oxygen (Φ ∆ = 0.4) when excited at 412 nm. Even after being conjugated onto the surface of the AuNRs, the molecular affinity of "KDKPPR" for NRP-1 was preserved. Under irradiation at 652 nm, in vitro assays were conducted on glioblastoma U87 cells incubated with different PS concentrations of free Pyro, intermediate PP-PS conjugate and hybrid AuNRs. The AuNRs showed no cytotoxicity in the absence of light even at high PS concentrations. However, they efficiently decreased the cell viability by 67% under light exposure. This nanosystem possesses good efficiency in PDT and an expected potential effect in a combined photodynamic/photothermal therapy guided by NIR fluorescence imaging of the tumors due to the presence of both the hyperthermic agent, AuNRs, and the fluorescent active phototoxic PS.

The Quantitative Proteomics Analysis in Glioblastoma After HULC Silencing

“…At present, it is treated mainly by surgery, radiotherapy and chemotherapy. Although some new methods of treatment are created, such as photodynamic therapy and immunotherapy, etc [2,3], their e cacy needs to be further evaluated. Disappointedly, the overall prognosis for GBM patients is poor currently.…”

<p>Multiscale Selectivity and in vivo Biodistribution of NRP-1-Targeted Theranostic AGuIX Nanoparticles for PDT of Glioblastoma</p>

“…This nanoparticle consists of an AGuIX design skeleton onto which has been grafted porphyrin molecules as PS agent and KDKPPR as targeting peptide. 27,28 This peptide moiety has been previously optimized by our group from a screening methodology based on the sequence homology of the domain encoded by exon 8a of VEGF 165 . 29 As affinity for NRP-1 receptor is an essential condition for VTP, emphasis has been placed on specific reference methods, namely SPR and complementary in vivo techniques such as a cranial window chamber model in order to face the obstacles inherent in brain tumors (blood-brain/tumor barrier).…”

Improvements in Gold Nanorod Biocompatibility with Sodium Dodecyl Sulfate Stabilization

“…All of these characteristics along with the fact that the biological transparency window (~600-1000 nm) coincides with the longitudinal plasmon band of GNRs, ref. [33] make gold nanorods suitable agents to aid in the clinical diagnosis and treatment of cancer with high accuracy and sensitivity, such as through CT-guided photothermal therapy [34,35], photodynamic therapy [36], and cancer radiotherapy [37].…”