ABSTRACT
Cancer radiotherapy suffers from drawbacks such as radiation resistance of hypoxic cells, excessive radiation that causes damage of adjacent healthy tissues, and concomitant side effects. Hence, radiotherapy sensitizers with improved radiotherapeutic performance and requiring a relatively small radiation dose are highly desirable. In this study, a nanosystem based on poly(lactic- co-glycolic acid) (PLGA) and ultrasmall black phosphorus quantum dots (BPQDs) is designed and prepared to accomplish precise tumor radiosensitization. The PLGA nanoparticles act as carriers to package the BPQDs to avoid off-target release and rapid degradation during blood circulation. The nanosystem that targets the polypeptide peptide motif Arg-Gly-Asp-Gys actively accumulates in tumor tissues. The 2,3-dimethylmaleic anhydride shell decomposes in an acidic microenvironment, and the nanoparticles become positively charged, thereby favoring cellular uptake. Furthermore, glutathione (GSH) deoxidizes the disulfide bond of cystamine and sequentially triggers release of BPQDs, rendering tumor cells sensitive to radiotherapy. The treatment utilizing the PLGA-SS-D@BPQDs nanosystem and X-ray induces cell apoptosis triggered by overproduction of reactive oxygen species. In the in vivo study, the nanosystem shows excellent radiotherapy sensitization efficiency but negligible histological damage of the major organs. This study provides insights into the design and fabrication of surface-charge-switching and pH-responsive nanosystems as potent radiosensitizers to achieve excellent radiotherapy sensitization efficacy and negligible toxic side effects.
Subject(s)
Antineoplastic Agents/pharmacology , Drug Delivery Systems , Melanoma/therapy , Phosphorus/chemistry , Quantum Dots/chemistry , Radiation-Sensitizing Agents/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Drug Screening Assays, Antitumor , Humans , Melanoma/metabolism , Melanoma/pathology , Melanoma, Experimental/metabolism , Melanoma, Experimental/pathology , Melanoma, Experimental/therapy , Mice , Mice, Nude , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Radiation-Sensitizing Agents/chemical synthesis , Radiation-Sensitizing Agents/chemistry , Reactive Oxygen Species/analysis , Reactive Oxygen Species/metabolism , Surface Properties , Tumor Cells, CulturedABSTRACT
In this study, polypeptide-based nanoparticles [constituted using poly(L-lysine) coupled with deoxycholic acid (DOCA) and conjugated with 2,3-dimethylmaleic acid (DMA)] have high tumor selectivity once electrostatically switched by the acidic milieu of solid tumors. These nanoparticles exhibited a significantly increased in vitro cellular uptake and high accumulation in the acidic tumor site in vivo. Consequently, Fe3O4-loaded nanoparticles enabled high contrast magnetic resonance (MR) imaging of the tumor in vivo.
Subject(s)
Contrast Media/chemistry , Deoxycholic Acid/analogs & derivatives , Magnetic Resonance Imaging , Magnetite Nanoparticles/chemistry , Polylysine/chemistry , Animals , Cell Line, Tumor , Deoxycholic Acid/chemistry , Female , Flow Cytometry , Humans , Mice, Nude , Microscopy, Confocal , Microscopy, Fluorescence , Neoplasms, Experimental/metabolism , Neoplasms, Experimental/pathology , Particle Size , Static Electricity , Surface PropertiesABSTRACT
SuperparamagneticSiO2@Fe3O4microspherewithcore-shellstructurewaspreparedbythe method of hydro-thermal and St?ber method, and modified by (3-aminopropyl) triethoxysilane ( APTES) . The obtained amino-Fe3 O4@SiO2 microsphere with controlled surface charge properties was characterized by SEM and TEM, and the surface electric property of amino-microsphere was investigated by Zeta potential measurement. The microsphere was used to extract DNA from human blood, and the solid phase extraction method by microspheres was developed. The mechanism of action between Aminated-Fe3 O4@SiO2 microsphere and DNA was explored, and the gel electrophoresis and PCR test were done on the extraction product. The result showed that genomic DNA with high purity was successfully extracted from whole blood by using amino-Fe3 O4@SiO2 microsphere, with the extraction rate about 70%, the saturated adsorption capacity for DNA was about 40 ng/μg, and the elution could be directly used for further bio-analysis.