Objective: In order to improve patient compliance and the ease of use during progesterone application, and to increase the clinical application of progesterone, progesterone was made into a microneedle. Methods: Progesterone complexes were prepared using a single-factor and central composite design. In the preparation of the microneedles, the tip loading rate was used as an evaluation index. The selection of tip materials among the biocompatible materials of gelatin (GEL), hyaluronic acid (HA), and polyvinylpyrrolidone (PVP), and the use of polyvinyl alcohol (PVA) and hydroxypropyl cellulose (HPC) as backing layers, respectively, were carried out and the resulting microneedles were evaluated accordingly. Results: The progesterone inclusion complexes prepared at a molar ratio of 1:2.16 progesterone and hydroxypropyl-β-cyclodextrin (HP-β-CD), a temperature of 50 °C, and reaction time of 4 h had high encapsulation and drug-loading capacities of 93.49% and 9.55%, respectively. Gelatine was finally chosen as the material for the preparation of the micro-needle tip based on the drug loading rate of the tip. Two types of microneedles were prepared: one with 7.5% GEL as the tip and 50% PVA as the backing layer, and one with 15% GEL as the tip and 5% HPC as the backing layer. The microneedles of both prescriptions exhibited good mechanical strength and penetrated the skin of rats. The needle tip loading rates were 49.13% for the 7.5% GEL-50% PVA microneedles and 29.31% for the 15% GEL-5% HPC microneedles. In addition, in vitro release and transdermal experiments were performed using both types of microneedles. Conclusion: The microneedles prepared in this study enhanced the in vitro transdermal amount of progesterone drug by releasing the drug from the microneedle tip into the subepidermis.

The combination of photodynamic therapy (PDT) and pneumatotherapy is emerging as one of the most effective strategies for increasing cancer treatment efficacy while minimizing side effects. Photodynamic forces affect nitric oxide (NO) levels as activated photosensitizers produce NO, and NO levels in the tumor and microenvironment directly impact tumor cell responsiveness to PDT. In this paper, 3-benzenesulfonyl-4-(1-hydroxy ether)-1,2,5-oxadiazole-2-oxide NO donor–silicon phthalocyanine coupling (SiPc–NO) was designed and prepared into self-assembled nanoparticles (SiPc–NO@NPs) by precipitation method. By further introducing arginyl-glycyl-aspartic acid (RGD) on the surface of nanoparticles, NO-photosensitizer delivery systems (SiPc–NO@RGD NPs) with photo-responsive and tumor-targeting properties were finally prepared and preliminarily evaluated in terms of their formulation properties, NO release, and photosensitizing effects. Furthermore, high reactive oxygen species (ROS) generation efficiency and high PDT efficiency in two breast cancer cell lines (human MCF-7 and mouse 4T1) under irradiation were also demonstrated. The novel SiPc–NO@RGD NPs show great potential for application in NO delivery and two-photon bioimaging-guided photodynamic tumor therapy.

Breast cancer is a common clinical malignant tumor that seriously threatens women’s physical and mental health. Chemotherapy, as the first choice of breast cancer treatment, has limited its application in the clinic due to problems of poor stability, short half-life, and serious toxic side effects. With the emergence of nanotechnology, inorganic materials to prepare mesoporous silica nanoparticles (MSNs) have been widely used in anti-tumor drug carriers. However, their slow degradation rate limits their application in the biomedical field. Therefore, developing low-toxicity MSNs with good biocompatibility, biodegradability, and rapid release at the tumor site is a key scientific issue to be addressed. Here, we prepared DOX-loaded Ca-Mg-doped MSNs by electrostatic adsorption to obtain Ca-Mg@DOX@MSNs with suitable particle sizes and zeta potential, and the incorporation of calcium and magnesium also led to an increase in the degradation rate under acidic conditions and an accelerated release, which reduced the toxicity of DOX and promoted cellular uptake with good anti-tumor effects. This study provides a new idea for the clinical treatment of breast cancer.

Glioblastoma, originating from glial cells in the brain's neuroepithelial tissue, are the most common primary malignant tumors of the central nervous system (CNS). Due to their invasive growth characteristics, most glioblastoma are difficult to completely resect, leaving residual tumor cells that become the source of recurrence. Harmine (HM), an active compound extracted from Peganum harmala L. seeds, exhibits a particularly notable in its anti-glioblastoma activity. However, HM suffers from poor selectivity, low bioavailability, and a tendency to enter the normal brain tissue, where it reversibly and competitively inhibits monoamine oxidase A (MAO-A), leading to neurotoxic side effects such as tremors and convulsions. To improve the therapeutic efficacy and reduce toxicity, this study fabricated a delivery system-based MNLs formulation modified with transferrin (Tf) on the surface (HM@MNLs-Tf). The high expression of TfR on glioma cells and blood-brain barrier endothelial cells (BMECs) facilitates the efficient crossing of the BBB and targeting of glioma cells. Additionally, the presence of iron oxide nanoparticles within HM@MNLs-Tf enhances BBB penetration when subjected to an external magnetic field (MF). This mechanism improves the selectivity of HM and reduces the neurotoxicity associated with MAO-A inhibition, thereby increasing its clinical applicability.​​ Results in vitro and in vivo demonstrated that the approach employed by this study significantly improved the therapeutic effect of HM to glioblastoma while minimizing its neurotoxicity and side effects.

Calcins represent a class of novel peptide ligands for ryanodine receptors (RyRs), demonstrating therapeutic potential against Ca²⁺ dysregulation-related cardiac diseases. Nevertheless, their biological effects beyond RyR modulation and underlying mechanisms remain unexplored. This study employed Opicalcin1 (OpiCa1), the most bioactive calcin member, revealing that while it reduced cytosolic Ca²⁺ in H9c2 cardiomyocytes, it concurrently diminished cell viability and promoted apoptosis. Transcriptomics and Western blot analyses identified suppression of the negatively regulatory PI3K/Akt pathway as the mechanistic basis. In acute/chronic in vivo studies, high-dose OpiCa1 (≥50 mg/kg i.v.) exhibited minimal impact on body weight, histopathology, and organ indices, while accompanied with subtle alterations in serum indicators, including slight elevations in AST, ALT, and LDH, alongside mild reductions in CK-MB and TBIL-Z. These findings unveil OpiCa1’s modulation on cardiomyocyte viability through PI3K/Akt inhibition with minimal systemic impact, providing new insights into non-RyR-mediated actions of calcins and critical toxicological support for developing calcin-based therapies targeting Ca²⁺-dysregulated cardiac pathologies.