Surface-modified silica nanoparticles for tumor-targeted delivery of camptothecin and its biological evaluation
ABSTRACT Here we report the design, synthesis and biological evaluation of surface-modified silica nanoparticles (SNP) for the delivery of camptothecin (CPT). Drug has been covalently linked to the nanoparticle through an ester bond with the 20-hydroxy moiety, in order to stabilize its lactone ring and to avoid unspecific release of the drug. The obtained material is highly stable in plasma, with low release of the cargo at physiological pH. Cell internalization and in vitro efficacy assays demonstrated that nanoparticles carrying CPT (SNP-CPT) entered cells via endocytosis and the intracellular release of the cargo induced cell death with half maximal inhibitory concentration (IC₅₀) values and cell cycle distribution profiles similar to those observed for the naked drug. Further, in vivo biodistribution, therapeutic efficacy and biocompatibility of the SNP-CPT were evaluated in human colorectal cancer xenografts using in vivo fluorescence or bioluminescence optical imaging. In vivo tumor-accumulation and whole-body tissue distribution were carried out based on the acquisition of fluorescence emission of a fluorophore (Cy5.5) conjugated to the SNP-CPT, as well as by HPLC quantification of tissue CPT levels. The results showed that, although SNP-CPT tended to accumulate in organs of the reticulo-endothelial system, nanoparticles boost CPT concentration in tumor vs administration of the free drug. Accordingly, SNP-CPT treatment delayed the growth of subcutaneous tumors while significantly reducing the systemic toxicity associated with CPT administration. These results indicate that the SNP-CPT could be used as a robust drug delivery system for antitumoral treatments based on CPT.
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ABSTRACT: Photodynamic therapy (PDT) of tumors causes skin photosensitivity as a result of unspecific accumulation behavior of the photosensitizers. PDT of tumors was improved by calcium phosphate nanoparticles conjugated with 1) mTHPC as photosensitizer, 2) the RGDfK-peptide for favored tumor targeting, and 3) the fluorescent dye molecule DY682-NHS for enabling near-infrared fluorescence (NIRF) optical imaging in vivo. The nanoparticles were characterized concerning size, spectroscopic properties, and uptake into CAL-27 cells. The nanoparticles had a hydrodynamic diameter of approximately 200 nm and a zeta potential of around +22 mV. Their biodistribution at 24 h after injection was investigated via NIRF optical imaging. After treating tumor-bearing CAL-27 mice with nanoparticle-PDT, the therapeutic efficacy was assessed by a fluorescent DY-734-annexin V probe at 2 days and 2 weeks after treatment to detect apoptosis. Additionally, the contrast agent IRDye(®) 800CW RGD was used to assess tumor vascularization (up to 4 weeks after PDT). After nanoparticle-PDT in mice, apoptosis in the tumor was detected after 2 days. A decrease of tumor vascularization as well as of tumor volume was detected in the next days after PDT. Calcium phosphate nanoparticles can be used as multifunctional tools for NIRF optical imaging, PDT, and tumor targeting as they exhibited a high therapeutic efficacy, were capable of inducing apoptosis and destroying tumor vascularization. Copyright © 2014. Published by Elsevier Ltd.Acta Biomaterialia 12/2014; 14. DOI:10.1016/j.actbio.2014.12.009 · 5.68 Impact Factor
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ABSTRACT: Colloidal carriers based on silica matrices are an innovative approach within the context of therapeutic drug delivery systems. These carriers are emerging as a great promise for diagnosis and treatment of a wide range of injuries, particularly in cancer and infection diseases. In addition, bioencapsulation for biosensing and cell therapy in silica sol-gel allows the survival of enzymes and cells for a long period of time. Due to their porosity, large surface area and high capability of functionalization, silica nanoparticles have been considered an attractive option for several bioanalysis applications, such as selective bioseparation, imaging and drug and gene delivery. However, although great advances are achieved in the biomedical fields, some toxicity effects can be associated to the use of silica nanoparticles. The present article aims to give a comprehensive review of recent technological advances for silica matrices in biomedical applications, as well the potential impact of silica-based materials to human health and environment. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Biotechnology and Applied Biochemistry 12/2014; DOI:10.1002/bab.1322 · 1.32 Impact Factor
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ABSTRACT: The present study is aimed to select the suitable method for preparation of camptothecin loaded polymeric nanoparticles by utilizing the multi-criteria decision making method. Novel approaches of drug delivery by formulation using nanotechnology are revolutionizing the future of medicine. Recent years have witnessed unprecedented growth of research and application in the area of nanotechnology. Nanoparticles have become an important area of research in the field of drug delivery because they have the ability to deliver a wide range of drug to varying areas of body. Despite of extensive research and development, polymeric nanoparticles are frequently used to improve the therapeutic effect of drugs. A number of techniques are available for the preparation of polymeric nanoparticles. The Analytical Hierarchy Process (AHP) is a method for decision making, which are derived from individual judgements for qualitative factors, using the pair-wise comparison matrix. In AHP, a decision hierarchy is constructed with a goal, criteria and alternatives. The model uses three main criteria 1) Instrument, 2) Process and Output and 3) Cost. In addition, there are eight sub-criteria's as well as eight alternatives. Pair-wise comparison matrixes are used to obtain the overall priority weight and ranking for the selection of suitable method. Nanoprecipitation technique is the most suitable method for the preparation of camptothecin loaded polymeric nanoparticles with the highest overall priority weight of 0.297 CONCLUSION: In particular, the result indicates that the priority weights obtained from AHP could be defined as a multiple output for finding out the most suitable method for preparation of camptothecin loaded polymeric nanoparticles.Advanced Pharmaceutical Bulletin 03/2015; 5(1):57-67. DOI:10.5681/apb.2015.008 · 0.88 Impact Factor