ABSTRACT
The applications of afterglow particles for photodynamic activation and biological imaging have become a topical research area. For these applications, it is critical to have water soluble nanoparticles. However, the synthesis of water soluble afterglow nanoparticles like Sr2MgSi2O7:Eu2+, Dy3+ is a challenging issue because most afterglow materials are very complicated in composition that cannot be synthesized by simple chemical routes. Here, for the first time, Sr2MgSi2O7:Eu2+, Dy3+ water soluble and stable nanoparticles are synthesize using a modified Sol-Gel method followed by the grinding and coating with APTES. The surface coating of the afterglow with APTES and the conjugation with PpIX and folic acid not only improve their water solubility but also enhance the PpIX luminescence by 10 times. More importantly, these strategies make it possible to produce singlet oxygen under X-ray irradiation, which is a very important result for deep cancer treatment. In addition, the surface coating and conjugation largely increase the cell uptake and greatly reduce their dark cytotoxicity. All these results indicate the methods reported here for afterglow nanoparticle synthesis, coating and conjugation are successful, and consequently, the prepared Sr2MgSi2O7:Eu2+, Dy3+/PPIX/Folic acid nano-conjugates are promising for X-ray induced photodynamic therapy on cancer treatment.
Subject(s)
Metal Nanoparticles/chemistry , Nanocapsules/chemistry , Photochemotherapy/methods , Propylamines/chemistry , Prostatic Neoplasms/drug therapy , Protoporphyrins/administration & dosage , Silanes/chemistry , Adsorption , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/radiation effects , Drug Compounding , Humans , Male , Metal Nanoparticles/administration & dosage , Metal Nanoparticles/ultrastructure , Nanocapsules/administration & dosage , Nanoconjugates/administration & dosage , Nanoconjugates/chemistry , Nanoconjugates/ultrastructure , Photosensitizing Agents/administration & dosage , Photosensitizing Agents/chemical synthesis , Prostatic Neoplasms/pathology , Protoporphyrins/chemistry , SolubilityABSTRACT
Afterglow nanoparticles have been widely investigated as new agents for cancer imaging and as a light source for photodynamic activation for cancer treatment. For both applications, the targeting of the afterglow nanoparticles to tumor cells is an important and challenging issue. Here we report the strategies for targeting Sr3MgSi2O8:Eu(2+),Dy(3+) afterglow nanoparticles to tumor cells by conjugating with variety of targeting molecules such as folic acid, RGD peptide, and R-11 peptide. For folic acid targeting, experimental observations were conducted on PC-3 cells (folate receptor negative), MCF-7 (folate receptor positive), and KB cells (folate receptor positive) to compare the cellular uptake and confirm targeted delivery. For the cyclic RGDfK peptide, experiments were carried out on the integrin αvß3 positive MDA-MB-231 breast cancer cell line and the integrin αvß3 negative MCF-7 breast cancer cell lines in order to compare the cellular uptakes. As for R11-SH peptide, cellular uptake of the afterglow nanoparticles was observed on LNCaP and PC3 prostate cancer cell lines. All the observations showed that the cellular uptakes of the nanoparticles were enhanced by conjugation to variety of targeting molecules which are specific for breast and prostate cancer cells.
Subject(s)
Luminescent Agents/chemical synthesis , Luminescent Agents/pharmacokinetics , Nanoconjugates/chemistry , Nanoparticles/chemistry , Neoplasms, Experimental/metabolism , Neoplasms, Experimental/pathology , Cell Line, Tumor , Humans , Materials Testing , Nanoconjugates/ultrastructure , Nanoparticles/ultrastructureABSTRACT
Molecular modification of protoporphyrin IX (PpIX) was conducted to improve its water solubility and therapeutic performance for photodynamic therapy. The carboxylic acid and the two nitrogen atoms in the core of PpIX molecule were protonated following by conjugation with 3-aminopropyl triethoxysilane (APTES). Then, folic acid (FA) was conjugated to the APTES-coated PpIX (MPpIX) through chemical bonding between FA and protonated PpIX. The results showed that APTES coating can stabilize PpIX and increase its water solubility. Consequently, this leads to the enhancement in luminescence and singlet oxygen production. Upon X-ray irradiation, singlet oxygen can be detected in the MPpIX but not in PpIX. This means that MPpIX can be used for deep cancer treatment as X-ray can penetrate deeply into tissue. Molecular modification also reduces the dark toxicity of PPIX and increases their cell uptake. All these traits indicate that the Molecular modification of PpIX may potentially improve the efficacy of photodynamic therapy for cancer treatment.
