Citation: Chavva, S.R.; Bhat, N.; San Juan, A.M.T.; Jaitpal, S.; Mabbott, S. Simultaneous Thermal and Spectroscopic Screening of Morphologically Complex Theranostic Gold Nanoparticles. J. Nanotheranostics 2022, 3, 102–116. https://doi.org/10.3390/jnt3020007 Academic Editors: Moein Moghimi, Chiara Martinelli and Emanuela Jacchetti Received: 9 March 2022 Accepted: 23 May 2022 Published: 26 May 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). Journal of Nanotheranostics Article Simultaneous Thermal and Spectroscopic Screening of Morphologically Complex Theranostic Gold Nanoparticles Suhash Reddy Chavva 1,2 , Namratha Bhat 1,2 , Angela Michelle T. San Juan 1,2 , Siddhant Jaitpal 1,2 and Samuel Mabbott 1,2, * 1 Health Technologies and Innovations Building, 3006 TAMU, College Station, TX 77843, USA; srchavva@tamu.edu (S.R.C.); namrathabhat@tamu.edu (N.B.); angelasanjuan08@tamu.edu (A.M.T.S.J.); sjaitpal@tamu.edu (S.J.) 2 Biomedical Engineering, Emerging Technologies Building, 3120 TAMU, College Station, TX 77843, USA * Correspondence: smabbott@tamu.edu Abstract: Gold nanoparticles absorb light energy and convert it to thermal energy that transfers to the surrounding environment, making them potentially useful for the hyperthermic treatments well known as photothermal therapy (PTT). Further, it is well documented that noble metal nanoparticles are capable of significantly enhancing the Raman scattering of molecules attached to their surfaces, a technique which is termed surface-enhanced Raman scattering (SERS). SERS combined with PTT has the ability to locate nanoparticles at depth and trigger heat production, providing an effective methodology to both seek and destroy diseased tissues. While PTT and SERS are often used in tandem and there are several ways of individually measuring SERS and thermal output, there is currently no method available that pre-screens both properties prior to in vitro or in vivo application. In this work, we have designed a 3D printed platform capable of coupling a commercially available Raman probe to a sample cuvette for SERS and heat output to be monitored simultaneously. We have compared the performance of morphologically complex gold nanoparticles, nanostars (AuNSs) and nanoplates (AuNPLs), which are both well utilized in SERS and photothermal experiments; and measured the SERS activity originating from common Raman reporter analytes 4-mercaptobenzoic acid (MBA) and 1,4-benzenedithiol (BDT). We were able to show that the system effectively measures the thermal output and SERS activity of the particles and can evaluate the effect that multiple irradiation cycles have on the SERS signal. Keywords: gold nanoparticles; photothermal effect; SERS; screening; MBA; BDT; nanostars; nanoplates; surface-enhanced Raman; Raman spectroscopy 1. Introduction The study of the plasmonic metallic nanoparticle-mediated photothermal effect (PTE) has gained enormous interest from a variety of fields due to the tunable optical response of nanoparticles and their adaptability for regulating photothermal conversion upon laser irradiation. PTE occurs when metal nanoparticles (NPs) absorb light and convert the energy for release as heat [1]. The heating effect is especially strong for metal NPs, since they have many mobile electrons delocalized from the metallic atoms [1]. Oscillating electrons transfer kinetic energy into the noble metal nanoparticle lattice through electron–phonon coupling, followed by phonon–phonon interactions with the surrounding medium [2,3]. These phonon–phonon interactions dissipate heat across a nanoparticle−matrix interface at a rate dependent on matrix type, particle size and laser power [4–6]. Photothermal therapy (PTT) is among the most popular applications of PTE, offering an alternative, minimally invasive, localized treatment method compared to existing treatments for the ablation of disease sites and the transdermally triggered release of drugs using NIR radiation. Gold nanoparticles (AuNPs) have been extensively studied to evaluate their therapeutic J. Nanotheranostics 2022, 3, 102–116. https://doi.org/10.3390/jnt3020007 https://www.mdpi.com/journal/jnt