Efficacy-shaping nanomedicine by loading Calcium Peroxide into Tumor Microenvironment-responsive Nanoparticles for the Antitumor Therapy of Prostate Cancer

Abstract

Rationale: Prostate cancer has become one of the most threatening malignant tumors in men, leading to an imperative need to develop effective and safe therapies. Because of the unique metabolism of tumor cells, the tumor microenvironment (TME) exhibits distinctive properties compared with normal tissues, among which the pH difference has been utilized as an ideal antitumor strategy. Herein, we introduce a reactive oxygen species (ROS)-controlled-release nanosystem with TME-responsiveness by applying hollow mesoporous silica nanoparticles (HMSNs) as carriers loaded with calcium peroxide (CaO 2 ) and coated with polyacrylic acid (PAA) to construct the functional material CaO 2 @HMSNs-PAA. The differences in pH values and exogenous ROS scavenging abilities between the tumor tissue and normal tissues and the dual pH-responsiveness from CaO 2 and PAA lay a scientific foundation for the application of CaO 2 @HMSNs-PAA in the tumor-selective therapy for prostate cancer. Methods: The morphology and the structure of the nanosystem were characterized by the transmission electron microscope, scanning electron microscope, energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, zeta potential, dynamic light scattering measurement, low-angle X-ray diffraction patterns and nitrogen adsorption/desorption isotherm. The CaO 2 loading capacity and release profiles in different buffer solutions were determined by inductively coupled plasma-mass spectrometry. The in vitro intracellular uptake of CaO 2 @HMSNs-PAA was explored on the PC-3 prostate cancer cell line via confocal laser scanning microscopy. The CCK-8 cell proliferation assay was conducted to evaluate the cytotoxicity of CaO 2 @HMSNs-PAA against PC-3 cells. ROS produced by CaO 2 @HMSNs-PAA was observed by a fluorescence microscope. The flow cytometry was utilized to analyze the apoptosis of PC-3 cells induced by CaO 2 @HMSNs-PAA. The Western blot analysis was performed to detect expressions of critical mitochondria-mediated apoptosis markers in PC-3 cells after incubation with CaO 2 @HMSNs-PAA. The in vivo biosafety and antitumor efficacy were evaluated out on BALB/c mice and BALB/c nude mice subcutaneously transplanted with PC-3 cells, respectively. Results: Comprehensive characterizations indicated the successful synthesis of CaO 2 @HMSNs-PAA with significant TME-responsiveness. The experimental results demonstrated that the well-developed nanocarrier could efficiently deliver CaO 2 to the tumor site and release ROS in response to the decreased pH value of TME, exerting ideal antitumor effects both in vitro and ...

Prussian Blue/Calcium Peroxide Nanocomposites-Mediated Tumor Cell Iron Mineralization for Treatment of Experimental Lung Adenocarcinoma

“…Besides, the anticancer efficiency of HC was further verified by a live/dead cell assay of A549 cells (Figure S2A) and Transwell assays (Figure C,D and S2B) also demonstrated its strongest inhibitory effect on invasion and migration ability of A549 cells. This result can be attributed to the fact that the HC can be gradually internalized by the tumor cells (Figure S3A), and overproduced H 2 O 2 (Figure S3B) from CaO 2 created oxidative stress in the cellular environment, resulting in cell apoptosis . Besides, HC can introduce iron mineralization in cancer cells, and lung cancer cells (A549 and H1299) displayed a significant elevation in their cellular pH with increased treatment time, resulting in effective iron mineralization in tumor cells, while normal lung epithelial cells (Beas-2B) of that was less affected by HC treatment (Figures E,F and S4A,B).…”

Manipulating Intratumoral Fenton Chemistry for Enhanced Chemodynamic and Chemodynamic‐Synergized Multimodal Therapy

“…[ 7 ] More importantly, in‐depth studies of current clinical treatments can offer intuitive guidance for exploring appropriate new therapies. [ 8 ]…”

Is the Fixed Periodic Treatment Effective for the Tumor System without Complete Information?

“…In the experiment, mice were subcutaneously inoculated with A549 or H1975 suspension (~5×10 6 cells per mouse) in the left forelimb flank. [21][22][23] Tumor volume was generally measured by caliper two to three times a week, and calculated according to the formula V ¼ π � lengh � width 2 À � =6. [24][25][26] When tumor volume reached around 100 mm 3 , mice with A549 or H1975 were randomly grouped according to tumor volume and weight.…”

“…In this experiment, mice were subcutaneously inoculated with single or mixed cell suspension (~5×10 6 cells per mouse) in left forelimb flank. [21][22][23] The single cell suspension was a single A549, and the mixed cell suspension was a mixture of H1975 and A549 in equal proportions. For mice with single A549, FK866 was administered from day 0 to day 8 at a dose of 20 mg/kg/day.…”