Magnetic chitosan nanoparticles as a drug delivery system for targeting photodynamic therapy

Abstract. Photodynamic therapy (PDT) has become an increasingly recognized alternative to cancer treatment in clinic. However, PDT therapy agents, namely photosensitizer (PS), are limited in application as a result of prolonged cutaneous photosensitivity, poor water solubility and inadequate selectivity, which are encountered by numerous chemical therapies. Magnetic chitosan nanoparticles provide excellent biocompatibility, biodegradability, non-toxicity and water solubility without compromising their magnetic targeting. Nevertheless, no previous attempt has been reported to develop an in vivo magnetic drug delivery system with chitosan nanoparticles for magnetic resonance imaging (MRI) monitored targeting photodynamic therapy. In this study, magnetic targeting chitosan nanoparticles (MTCNPs) were prepared and tailored as a drug delivery system and imaging agents for PS, designated as PHPP. Results showed that PHPP-MTCNPs could be used in MRI monitored targeting PDT with excellent targeting and imaging ability. Non-toxicity and high photodynamic efficacy on SW480 carcinoma cells both in vitro and in vivo were achieved with this method at the level of 0–100 µM. Notably, localization of nanoparticles in skin and hepatic tissue was significantly less than in tumor tissue, therefore photosensitivity and hepatotoxicity can be attenuated.

Print publication: Issue 13 (1 April 2009)
Received 18 November 2008, in final form 20 January 2009
Published 10 March 2009

Studies on Preparation of Photosensitizer Loaded Magnetic Silica Nanoparticles and Their Anti-Tumor Effects for Targeting Photodynamic Therapy

Zhi-Long Chen1, Yun Sun1, Peng Huang1, Xiao-Xia Yang1 and Xing-Ping Zhou1
(1) Department of Pharmaceutical Science and Technology, College of Chemistry and Biology, Donghua University, Shanghai, 201620, China
Received: 13 November 2008 Accepted: 8 January 2009 Published online: 31 January 2009

Abstract As a fast developing alternative of traditional therapeutics, photodynamic therapy (PDT) is an effective, noninvasive, nontoxic therapeutics for cancer, senile macular degeneration, and so on. But the efficacy of PDT was compromised by insufficient selectivity and low solubility. In this study, novel multifunctional silica-based magnetic nanoparticles (SMNPs) were strategically designed and prepared as targeting drug delivery system to achieve higher specificity and better solubility. 2,7,12,18-Tetramethyl-3,8-di-(1-propoxyethyl)-13,17-bis-(3-hydroxypropyl) porphyrin, shorted as PHPP, was used as photosensitizer, which was first synthesized by our lab with good PDT effects. Magnetite nanoparticles (Fe3O4) and PHPP were incorporated into silica nanoparticles by microemulsion and sol–gel methods. The prepared nanoparticles were characterized by transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy and fluorescence spectroscopy. The nanoparticles were approximately spherical with 20–30 nm diameter. Intense fluorescence of PHPP was monitored in the cytoplasm of SW480 cells. The nanoparticles possessed good biocompatibility and could generate singlet oxygen to cause remarkable photodynamic anti-tumor effects. These suggested that PHPP-SMNPs had great potential as effective drug delivery system in targeting photodynamic therapy, diagnostic magnetic resonance imaging and magnetic hyperthermia therapy.
Graphical Abstract Novel multifunctional photosensitizer loaded magnetic silica nanoparticles were strategically prepared with low toxicity, good biocompatibility and remarkable photodynamic anti-tumor efficacy. The nanoparticles were believed to be of great value as drug delivery system in targeting photodynamic therapy, diagnostic magnetic resonance imaging and magnetic hyperthermia therapy.

Dual-modality in vivo imaging using rare-earth nanocrystals with near-infrared to near-infrared (NIR-to-NIR) upconversion luminescence and magnetic resonance properties

^a Department of Chemistry & Advanced Materials Laboratory, Fudan University, 220 Handan Road, Shanghai 200433, P.R. China

^b Shanghai Key Laboratory of Magnetic Resonance, Physics Department, East China Normal University, Shanghai 200062, P.R. China

Received 24 November 2009;accepted 9 January 2010.Available online 4 February 2010.

Abstract

Upconversion luminescence (UCL) imaging is expected to play a significant role in future photoluminescence imaging since it shows advantages of sharp emission lines, long lifetimes, superior photostability and no blinking. To further improve penetration depth, herein, near-infrared to near-infrared (NIR-to-NIR) UCL and magnetic properties were combined into a nanoparticle, and NIR-to-NIR UCL and MRI dual-modal bioimaging in vivo of whole-body animal were developed. Hydrophilic and carboxylic acid-functionalized Tm³⁺/Er³⁺/Yb³⁺ co-doped NaGdF₄ upconversion nanophosphors (AA-NPs) were synthesized and showed both NIR-to-visible and NIR-to-NIR luminescence under excitation of 980 nm. Collecting the signal of the upconversion emission from AA-NPs in the visible and NIR range, all UCL imaging of cells, tissues and whole-body animals with different penetration depth showed high contrast. Moreover, AA-NPs showed a high relaxivity of 5.60 s⁻¹ (mm)⁻¹ and were successfully applied as contrast agents for magnetic resonance imaging (MRI) in vivo. By means of the combination of UCL imaging and MRI, the distribution of AA-NPs in living animals was studied, and the results indicated that these particles mainly accumulate in the liver and spleen without undesirable stay in the lungs. Therefore, the concept of UCL and MR dual-modality imaging in vivo of whole-body animals using Tm³⁺/Er³⁺/Yb³⁺ co-doped NaGdF₄ with NIR-to-NIR upconversion luminescent and magnetic resonance properties can serve as a platform technology for the next-generation of probes for bioimaging in vivo.