Citation: Karayianni, M.; Koufi, D.; Pispas, S. Development of Double Hydrophilic Block Copolymer/ Porphyrin Polyion Complex Micelles towards Photofunctional Nanoparticles. Polymers 2022, 14, 5186. https://doi.org/10.3390/ polym14235186 Academic Editor: Nikolaos Politakos Received: 31 October 2022 Accepted: 22 November 2022 Published: 29 November 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/). polymers Article Development of Double Hydrophilic Block Copolymer/Porphyrin Polyion Complex Micelles towards Photofunctional Nanoparticles Maria Karayianni , Dimitra Koufi and Stergios Pispas * Theoretical and Physical Chemistry Institute, National Hellenic Research Foundation, 48 Vassileos Constantinou Avenue, 116 35 Athens, Greece * Correspondence: pispas@eie.gr Abstract: The electrostatic complexation between double hydrophilic block copolymers (DHBCs) and a model porphyrin was explored as a means for the development of polyion complex micelles (PICs) that can be utilized as photosensitive porphyrin-loaded nanoparticles. Specifically, we em- ployed a poly(2-(dimethylamino) ethyl methacrylate)-b-poly[(oligo ethylene glycol) methyl ether methacrylate] (PDMAEMA-b-POEGMA) diblock copolymer, along with its quaternized polyelec- trolyte copolymer counterpart (QPDMAEMA-b-POEGMA) and 5,10,15,20-tetraphenyl-21H,23H- porphine-p,p ′ ,p”,p ′′′ -tetrasulfonic acid tetrasodium hydrate (TPPS) porphyrin. The (Q)PDMAEMA blocks enable electrostatic binding with TPPS, thus forming the micellar core, while the POEGMA blocks act as the corona of the micelles and impart solubility, biocompatibility, and stealth properties to the formed nanoparticles. Different mixing charge ratios were examined aiming to produce stable nanocarriers. The mass, size, size distribution and effective charge of the resulting nanoparticles, as well as their response to changes in their environment (i.e., pH and temperature) were investigated by dynamic and electrophoretic light scattering (DLS and ELS). Moreover, the photophysical properties of the complexed porphyrin along with further structural insight were obtained through UV-vis (200-800 nm) and fluorescence spectroscopy measurements. Keywords: double hydrophilic block copolymers; porphyrins; polyion complex micelles; photosensitizers 1. Introduction Successful cancer treatment is one of the most sought-after goals of modern-day medicine, since cancer remains a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020 according to the World Health Organization [1]. Among the various proposed therapeutic strategies, photodynamic therapy (PDT) holds significant promise owing to its efficiency, site-specificity, and noninvasive characteristics. It is being used not only for the treatment of tumors related to various types of cancers (e.g., skin, esophageal, lung) but also a number of other diseases and medical conditions, such as atherosclerosis, rheumatoid arthritis, macular degeneration, psoriasis, and acne [2]. The working principle of PDT is based on the administration of photosensitizers that accumulate in pathological tissue and are subsequently exposed to a light source with appropriate wavelength so as to generate the production of reactive oxygen species (ROS), which in turn cause cell death [3–6]. Due to its selective action, it causes minimal damage to the surrounding healthy tissue, has no severe local or systemic side effects, is not painful, is well tolerated by patients, allows for outpatient use, and can even be applied in parallel with other therapeutic protocols [2,3]. All these advantages in combination with documented good therapeutic results render PDT a widespread contemporary method for the treatment of cancer and other infectious diseases. Evidently, the role of the photosensitizer is of utmost importance for the effective application of PTD. Having entered the cell, the photoactive molecule is appropriately irradiated, leading to its excitation from the ground to the excited singlet state as a result Polymers 2022, 14, 5186. https://doi.org/10.3390/polym14235186 https://www.mdpi.com/journal/polymers