Protein-Poly(amino acid) Nanocore–Shell Mediated Synthesis of Branched Gold Nanostructures for Computed Tomographic Imaging and Photothermal Therapy of Cancer

Abstract

Anisotropic noble metal nanoparticles especially branched gold nanoparticles with a large absorption cross-section and high molar extinction coefficient have promising applications in biomedical field. However, sophisticated and cumbersome methodologies of synthesis along with toxic precursors pose serious concern for its use. Herein, we report the synthesis of branched gold nanostructures from protein (albumin) nanoparticles by a simple reduction method. Albumin nanoparticles were synthesized by a modified desolvation technique with poly-l-arginine (cationic poly amino acid) substituting the conventional toxic cross-linker, glutaraldehyde. In silico molecular docking was carried out to study the interaction of poly-l-arginine with albumin which revealed its binding to Pocket 1B of the A-chain of albumin. The poly-l-arginine-albumin core-shell nanoparticles of ∼100 nm in size served as a base for attachment of gold ions and its reduction to form 140 nm sized branched gold nanostructures conjugated with glutathione. These gold nanostructures exhibited near-infrared absorption λmax at 800 nm with extreme compatibility toward non cancerous (NIH 3T3), oral epithelial carcinoma (KB) cell lines, and human blood (red blood cells, platelets, and coagulation mechanisms) even up to a high concentration of 250 μg/mL. These structures demonstrated superior computed tomographic (CT) contrast ability and marked photothermal cytotoxicity on KB cells. This study reports for the first time a method to develop blood and cell compatible branched gold nanostructures from protein nanoparticles as a dual CT diagnostic and photothermal therapeutic agent.

Strategies for Preparing Albumin-based Nanoparticles for Multifunctional Bioimaging and Drug Delivery

“…Albumin-stabilized nanoparticles could be used as nanocarriers for both drug delivery and contrast agent delivery or be directly applied in bioimaging 223 . Thus, the designed hybrid nanoparticle could be used for both imaging and therapy 224 , 225 .…”

“…The obtained multifunctional nanoparticle was successfully applied in synergistic PDT/PTT. Albumin-stabilized branched gold nanostructure could also be used for X-CT guided PTT on cancer 224 .…”

Fluidic Manufacture of Star‐Shaped Gold Nanoparticles

“…The core, as an antenna, produces a magnetic field enhancement of the tip plasmons and consequently LSPR can be affected by spike morphology and number. These unique properties can be exploited in many applications like surface‐enhanced Raman spectroscopy (SERS), biosensing, photonic, photo‐thermal therapy, and even for photo‐catalytic applications . To date, due to the increasing demand in specific applications, the design of AuNPs with tailored LSPRs remains an active area of research .…”

“…To prepare NPs suitable for a vast pool of applications, it is crucial to coat their surface with specific functionalization that confers peculiar properties to the nanosystem (i.e. stability in a medium, active targeting or chemical‐physical activity).…”

The effect of nanoencapsulation of ICG on two-photon bioimaging

“…[33][34][35][36][37][38][39] Additionally, it is a semi-essential amino-acid with various roles such as in cell metabolism, wound healing, protein synthesis, and it also shows antimicrobial and antitumor activity. [40][41][42][43][44][45] In particular, owing to their favorable properties, NPs comprised of PLA have garnered considerable interest for delivery of small molecules. [46][47][48] Hence, the synthesis of ICG-PLA NPs would not only help in cellular delivery but also would improve the optical stability of ICG.…”