Melike Sessevmez

Cancer is a leading cause of death in the world today. In addition to the side effects of the chemotherapeutic drugs used to treat cancer, the development of resistance to the drugs renders the existing drugs ineffective. Therefore, there is an urgent need to develop novel anticancer agents. Medicinally important phytochemicals such as curcumin, naringenin, quercetin, epigallocatechin gallate, thymoquinone, kaempferol, resveratrol, genistein, and apigenin have some drawbacks, including low solubility in water, stability and bioavailability issues, despite having significant anticancer effects. Encapsulation of these natural compounds into polymer nanoparticles (NPs) is a novel technology that could overcome these constraints. In comparison to the free compounds, phytochemicals loaded into nanoparticles have greater activity and bioavailability against many cancer types. In this review, we describe the preparation and characterization of natural phytochemical-loaded polymer NP formulations with significant antioxidant and anti-inflammatory effects, their in vitro and in vivo anticancer activities, as well as their possible cellular targets.

This study focuses on creating a specialized nanogel for targeted drug delivery in cancer treatment, specifically targeting prostate cancer. This nanogel (referred to as SGK 636/Peptide 563/PEtOx nanogel) is created using hydrophilic poly(2‐ethyl‐2‐oxazoline) (PEtOx) through a combination of living/cationic ring‐opening polymerization (CROP) and alkyne‐azide cycloaddition (CuAAC) “click” chemical reactions. A fluorescent probe (BODIPY) is also conjugated with the nanogel to monitor drug delivery. The characterizations through ¹H‐NMR, and FT‐IR, SEM, TEM, and DLS confirm the successful production of uniform, and spherical nanogels with controllable sizes (100 to 296 nm) and stability in physiological conditions. The biocompatibility of nanogels is evaluated using MTT cytotoxicity assays, revealing dose‐dependent cytotoxicity. Drug‐loaded nanogels exhibited significantly higher cytotoxicity against cancer cells in vitro compared to drug‐free nanogels. Targeting efficiency is examined using both peptide‐conjugated and peptide‐free nanogels, with the intracellular uptake of peptide 563‐conjugated nanogels by tumor cells being 60‐fold higher than that of nanogels without the peptide. The findings suggest that the prepared nanogel holds great potential for various drug delivery applications due to its ease of synthesis, tunable functionality, non‐toxicity, and enhanced intracellular uptake in the tumor region.

Photodynamic therapy facilitates the selective destruction of cancer tissue by utilizing a photosensitizer drug, the light near the absorbance wavelength of the drug, and oxygen. Methylene Blue, 5-aminolevulinic acid (the precursor of the photosensitizer, protoporphyrin IX), porphyrin, Foscan, Chlorin e6, and HPPH have been used successfully as photosensitizers in the treatment of oral verrucous hyperplasia, oral leukoplakia, oral lichen planus, and head and neck squamous cell carcinoma. “Theranostic” liposomes can deliver a contrast agent for magnetic resonance imaging and a photosensitizer for the image-guided photodynamic therapy of head and neck cancer. Liposomes incorporating photosensitizers can be targeted to cell surface markers overexpressed on cancer cells. Novel porphyrinoids have been developed in our laboratories that are highly effective as photosensitizers. Tribenzoporphyrazines encapsulated in cationic liposomes have produced IC₅₀ values up to 50 times lower compared to the free photosensitizers. It is anticipated that targeting these drugs to cancer stem cells, using upconversion nanoparticles for the near-infrared irradiation of tumors to activate the photosensitizers, and overcoming tumor hypoxia will enhance the efficacy of photodynamic therapy of tumors accessible to light sources.

In this study, prostate cancer-targeted, drug-loaded PEtOx nanogel was prepared by the combination of living/cationic ring-opening polymerization and alkyne-azide cycloaddition “click” chemistry. A fluorescence probe was also conjugated with nanogel to track drug delivery. Nanogel formation was confirmed by 1H-NMR and FT-IR spectroscopies while SEM and DLS analyses showed uniform spherical nanogels and the particle size of nanogels could be controlled at 100-250 nm with relatively narrow size distributions. The physical stability of nanogels has been examined at pH 7.4 and %1-5 fetal bovine serum and intravenously administered nanogel formulations could remain in the bloodstream without much physical change until they reach the target site. The biocompatibility of the nanogels was evaluated using MTT cytotoxicity assays. The results showed that cytotoxicity was dose-dependent and drug-loaded nanogels against cancer cells in vitro were much higher than that of the drug-free nanogel. The targeting efficiency was examined with peptide conjugated and peptide-free nanogel. Intracellular uptake of peptide 563 conjugated nanogel by tumor cells was 60-fold higher than that of nanogel without peptide. Our findings suggest that prepared nanogel exhibits great potential to be used in a variety of drug delivery applications due to non-toxic, and enhanced intracellular uptake into the tumor region.

Antibiotic-resistant infections present a serious health concern worldwide. It is estimated that there are 2.8 million antibiotic-resistant infections and 35,000 deaths in the United States every year. Such microorganisms include Acinetobacter, Enterobacterioceae, Pseudomonas, Staphylococcus and Mycobacterium. Alternative treatment methods are, thus, necessary to treat such infections. Bacteriophages are viruses of bacteria. In a lytic infection, the newly formed phage particles lyse the bacterium and continue to infect other bacteria. In the early 20th century, d’Herelle, Bruynoghe and Maisin used bacterium-specific phages to treat bacterial infections. Bacteriophages are being identified, purified and developed as pharmaceutically acceptable macromolecular “drugs,” undergoing strict quality control. Phages can be applied topically or delivered by inhalation, orally or parenterally. Some of the major drug-resistant infections that are potential targets of pharmaceutically prepared phages are Pseudomonas aeruginosa, Mycobacterium tuberculosis and Acinetobacter baumannii.

Treatment of patients with bisphosphonate usage is a significant concern for oral surgeons because it interferes with jaw bone turnover and regeneration. In case of adverse effects manifesting related to bisphosphonate use, oral surgeons are usually treating and keep the patient’s symptoms under control. In this study, we aimed to investigate a new treatment protocol for medication-related osteonecrosis of the jaw (MRONJ). This treatment protocol consisted of administering human parathyroid hormone (hPTH) loaded chitosan microspheres which were prepared by ionotropic gelation method or/and the prepared microspheres were suspended in a poloxamer gel. After in-vitro optimization studies, the efficacy of the chosen formulations was evaluated in-vivo studies. Zoledronic acid was administered daily to forty-eight adult female Sprague-Dawley rats, divided into four experimental groups, at a daily concentration of 0.11 mg/kg over three weeks to induce the MRONJ model. At the end of this period, maxillary left molar teeth were extracted. In the first group, the subjects received no treatment. In the negative control group, poloxamer hydrogel containing empty microspheres were immediately applied to the soft tissues surrounding the extraction socket. The treatment group-1 was treated with local injections of poloxamer hydrogel containing hPTH. The treatment group-2 was treated with a single local injection of poloxamer hydrogel containing hPTH-loaded chitosan microspheres. Both treatment groups received a total of 7 µg of hPTH at the end of the treatment protocol. Our study demonstrates successful attenuation of MRONJ through a local drug delivery system combined with hPTH, as opposed to previously attempted treatment strategies.