Photodynamic Therapy (PDT) is based on the combination of three pillars: light at an appropriate wavelength, a photosensitizer (PS), and the presence of molecular oxygen to generate reactions that trigger the formation of singlet oxygen, which is primarily responsible for the destruction of the treatment target. PDT can be applied in treating several neoplastic and non-oncological diseases, presenting superior characteristics to conventional treatments, such as selectivity and minimizing side effects [1], [2], [3].

Phthalocyanine (Pc) is a synthetic dye that consists of four isoindole rings connected by four nitrogen atoms [4]. Pc is an alternative to porphyrins since PSs do not absorb in the 400–600 nm range, having no phototoxicity to the skin. Unlike porphyrins, Pc has absorption and fluorescence wavelengths in the 650–800 nm and high singlet oxygen production. However, like porphyrins, Pc can form metal complexes that increase the ability to produce singlet oxygen [5].

Chloroaluminium phthalocyanine (ClAlPc) is a chemically stable and commercially available photosensitizer active for PDT protocols. However, the poor solubility of unsubstituted metal-phthalocyanines and their high molecular weight (574.96 g.mol-1 for ClAlPc) are some of the significant concerns regarding its physiological medium use [6].

Thus, ClAlPc has been encapsulated in different nanocarriers, such as liposomes, polymeric nanoparticles, and nanoemulsions, and tested against different eukaryotic cells, showing higher activity in cell inhibition [7], [8], [9], [10].

Hydroxyapatite (HAp) is like human bone structure, in addition to numerous favorable properties for its use as DDS: biocompatibility, biodegradability, osseointegrity, hardness and resistance [11,12]. Sang et al. (2019) synthesized HAp nanorods by the hydrothermal method as the basis for a composite with graphene oxide for the delivery of dexorubicin (DOX) for application in cancer treatments [13]. Feng et al. (2013) used hydrothermal to synthesize HAp from vaterite templates. They used it as a basis for synthesizing hollow microparticles of chitosan, HAp, and sodium alginate for DOX delivery [14]. Qiet al. (2013) synthesized hollow HAp microspheres using microwaves as an ibuprofen and hemoglobin delivery system. HAp is a versatile material tool used in several areas, such as implant coating, release, and components of chromatographic systems, among others [15].

The hydrothermal method is based on applying high pressure and high temperature to aqueous solutions in the controlled environment of an autoclave. Liu et al. (2003) studied the influence of pH and temperature on the synthesis of HAp. They found that values of pH 6 and 9 and temperatures of up to 120 °C proved to be the best for obtaining a pure material with characteristics like the standards in the literature [16].

Lai et al. (2016) synthesized hollow HAp microspheres starting from vaterite templates and using the hydrothermal method for 1 h (120 °C), producing urchin-shaped structures with a size of approximately 2 µm [17]. Daryan et al. (2020) conducted a study using hydrothermal treatment at a temperature of 180 °C for various periods: 30 min resulted in an aggregate of 20 µm particles. After 1 h, 1 µm microspheres were formed; after 2 h, 1 µm nanosheets were formed [18].

Gliosarcoma is a malignant tumor presenting two aspects: superficial and deeper in the tissue. Both cases are treated with surgery and chemotherapy, but the best treatment methodology has yet to be defined in the literature [[19], [20]].

This work's objective was synthesizing hydroxyapatite microspheres from vaterite templates to realize the characterization of morphology, structure, and properties and to use them as a modified delivery system in treating a cultured Gliosarcoma strain9l/lacZ. This work is the first study in a drug delivery system with ClAlPc-loaded hydroxyapatite microspheres from vaterite templates using a 9 L/lacZ cell line as a biological PDT protocol application model.