ABSTRACT
Protein-based materials are usually considered as insulators, although conductivity has been recently shown in proteins. This fact opens the door to develop new biocompatible conductive materials. While there are emerging efforts in this area, there is an open challenge related to the limited conductivity of protein-based systems. This work shows a novel approach to tune the charge transport properties of protein-based materials by using electron-dense AuNPs. Two strategies are combined in a unique way to generate the conductive solid films: (1) the controlled self-assembly of a protein building block; (2) the templating of AuNPs by the engineered building block. This bottom-up approach allows controlling the structure of the films and the distribution of the AuNPs within, leading to enhanced conductivity. This work illustrates a promising strategy for the development of effective hybrid protein-based bioelectrical materials.
Subject(s)
Doping in Sports , Metal Nanoparticles , Electric Conductivity , Gold , ProteinsABSTRACT
There is still a need for improving the treatment of breast cancer with doxorubicin (DOX). In this paper, we functionalized magnetic nanoparticles (MNPs) with DOX and studied the DOX-induced antitumor effects in breast cancer cells (BT474) in the presence of magnetic hyperthermia (43 °C, 1 h). We show that i) intratumoral application of DOX-functionalized MNPs (at least at a concentration of 9.6 nmol DOX/100 mm3 tumor volume) combined with magnetic hyperthermia favors tumor regression in vivo, and there is evidence for an increased effect compared to magnetic hyperthermia alone or to the intratumoral application of free DOX and ii) the presence of the pseudopeptide NucAnt (N6L) on the MNP surface might well be beneficial in its function as carrier for MNP internalization into breast cancer cells in vitro, which could further augment the possibility of the induction of intracellular heating spots and cell death in the future.
ABSTRACT
In this paper we show that conjugation of magnetic nanoparticles (MNPs) with Gemcitabine and/or NucAnt (N6L) fostered their internalization into pancreatic tumor cells and that the coupling procedure did not alter the cytotoxic potential of the drugs. By treating tumor cells (BxPC3 and PANC-1) with the conjugated MNPs and magnetic hyperthermia (43⯰C, 60â¯min), cell death was observed. The two pancreatic tumor cell lines showed different reactions against the combined therapy according to their intrinsic sensitivity against Gemcitabine (cell death, ROS production, ability to activate ERK 1/2 and JNK). Finally, tumors (e.g. 3â¯mL) could be effectively treated by using almost 4.2â¯×â¯105 times lower Gemcitabine doses compared to conventional therapies. Our data show that this combinatorial therapy might well play an important role in certain cell phenotypes with low readiness of ROS production. This would be of great significance in distinctly optimizing local pancreatic tumor treatments.
Subject(s)
Hyperthermia, Induced , Magnetite Nanoparticles/chemistry , Pancreatic Neoplasms/pathology , Animals , Apoptosis/drug effects , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Deoxycytidine/analogs & derivatives , Deoxycytidine/pharmacology , Humans , JNK Mitogen-Activated Protein Kinases/metabolism , Ki-67 Antigen/metabolism , Magnetite Nanoparticles/ultrastructure , Mice, Nude , Peptides/pharmacology , Phenotype , S Phase/drug effects , Tumor Burden/drug effects , Xenograft Model Antitumor Assays , GemcitabineABSTRACT
This chapter will focus on the description of protein-based nanostructures. How proteins can be used as molecular units in order to generate complex materials and structures? What are the key aspects to achieve defined final properties, including shape, stability, function, and order at different length scales by modifying the protein sequence at the modular level?As described in other chapters of the book, we will review the basic concepts and the latest achievements in protein engineering toward nanotechnological applications. Particularly in this chapter the main focus will be on a particular type of proteins, repeat proteins. Because of their modular nature, these proteins are better suited to be used as building blocks than other protein scaffolds. First, we describe general concepts of the protein-based assemblies. Then we introduce repeat proteins and describe the properties that will impact their use in nanotechnology. In particular, we focus on a system based on a synthetic protein, the consensus tetratricopeptide repeat (CTPR). We review recent works from other groups and our group in which the potential of these repeat protein scaffolds is exploited for the fabrication of different protein assemblies, and as biomolecular templates to arrange different molecules and nanoscale objects.
Subject(s)
Nanostructures/chemistry , Protein Engineering/methods , Proteins/chemistry , Repetitive Sequences, Amino Acid , Proteins/geneticsABSTRACT
The controlled assembly of building blocks to achieve new nanostructured materials with defined properties at different length scales through rational design is the basis and future of bottom-up nanofabrication. This work describes the assembly of the idealized protein building block, the consensus tetratricopeptide repeat (CTPR), into monolayers by oriented immobilization of the blocks. The selectivity of thiol-gold interaction for an oriented immobilization has been verified by comparing a non-thiolated protein building block. The physical properties of the CTPR protein thin biomolecular films including topography, thickness, and viscoelasticity, are characterized. Finally, the ability of these scaffolds to act as templates for inorganic nanostructures has been demonstrated by the formation of well-packed gold nanoparticles (GNPs) monolayer patterned by the CTPR monolayer.
Subject(s)
Gold/chemistry , Immobilized Proteins/chemistry , Metal Nanoparticles/chemistry , Proteins/chemistry , Adsorption , Metal Nanoparticles/ultrastructure , Microscopy, Atomic Force , Microscopy, Electron, Scanning , Nanostructures/chemistry , Nanostructures/ultrastructure , Sulfhydryl Compounds/chemistry , Surface Plasmon Resonance , Surface Properties , Viscoelastic Substances/chemistryABSTRACT
Nanomedicine nowadays offers novel solutions in cancer therapy and diagnosis by introducing multimodal treatments and imaging tools in one single formulation. Nanoparticles acting as nanocarriers change the solubility, biodistribution and efficiency of therapeutic molecules, reducing their side effects. In order to successfully apply these novel therapeutic approaches, efforts are focused on the biological functionalization of the nanoparticles to improve the selectivity towards cancer cells. In this work, we present the synthesis and characterization of novel multifunctionalized iron oxide magnetic nanoparticles (MNPs) with antiCD44 antibody and gemcitabine derivatives, and their application for the selective treatment of CD44-positive cancer cells. The lymphocyte homing receptor CD44 is overexpressed in a large variety of cancer cells, but also in cancer stem cells (CSCs) and circulating tumor cells (CTCs). Therefore, targeting CD44-overexpressing cells is a challenging and promising anticancer strategy. Firstly, we demonstrate the targeting of antiCD44 functionalized MNPs to different CD44-positive cancer cell lines using a CD44-negative non-tumorigenic cell line as a control, and verify the specificity by ultrastructural characterization and downregulation of CD44 expression. Finally, we show the selective drug delivery potential of the MNPs by the killing of CD44-positive cancer cells using a CD44-negative non-tumorigenic cell line as a control. In conclusion, the proposed multifunctionalized MNPs represent an excellent biocompatible nanoplatform for selective CD44-positive cancer therapy in vitro.
Subject(s)
Ferric Compounds/chemistry , Hyaluronan Receptors/metabolism , Nanoparticles/chemistry , Cell Line, Tumor , Chemistry, Pharmaceutical/methods , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Deoxycytidine/chemistry , Drug Carriers/administration & dosage , Drug Carriers/chemistry , Drug Delivery Systems/methods , Ferric Compounds/administration & dosage , Humans , Magnetics/methods , Nanomedicine/methods , Nanoparticles/administration & dosage , Neoplastic Cells, Circulating/metabolism , Neoplastic Stem Cells/metabolism , Tissue Distribution/physiology , GemcitabineABSTRACT
Proteins have been used as templates to stabilize fluorescent metal nanoclusters thus obtaining stable fluorescent structures, and their fluorescent properties being modulated by the type of protein employed. Designed consensus tetratricopeptide repeat (CTPR) proteins are suited candidates as templates for the stabilization of metal nanoclusters due to their modular structural and functional properties. Here, we have studied the ability of CTPR proteins to stabilize fluorescent gold nanoclusters giving rise to designed functional hybrid nanostructures. First, we have investigated the influence of the number of CTPR units, as well as the presence of cysteine residues in the CTPR protein, on the fluorescent properties of the protein-stabilized gold nanoclusters. Synthetic protocols to retain the protein structure and function have been developed, since the structural and functional integrity of the protein template is critical for further applications. Finally, as a proof-of-concept, a CTPR module with specific binding capabilities has been used to stabilize gold nanoclusters with positive results. Remarkably, the protein-stabilized gold nanocluster obtained combines both the fluorescence properties of the nanoclusters and the functional properties of the protein. The fluorescence changes in nanoclusters fluorescence have been successfully used as a sensor to detect when the specific ligand was recognized by the CTPR module.
Subject(s)
Adaptor Proteins, Vesicular Transport/chemistry , Ascorbic Acid/chemistry , Gold/chemistry , HSP90 Heat-Shock Proteins/chemistry , Heterotrimeric GTP-Binding Proteins/chemistry , Metal Nanoparticles/chemistry , Adaptor Proteins, Vesicular Transport/biosynthesis , Adaptor Proteins, Vesicular Transport/genetics , Amino Acid Sequence , Binding Sites , Drug Design , Escherichia coli/genetics , Escherichia coli/metabolism , Fluorescent Dyes , Gene Expression , HSP90 Heat-Shock Proteins/chemical synthesis , Heterotrimeric GTP-Binding Proteins/biosynthesis , Heterotrimeric GTP-Binding Proteins/genetics , Ligands , Metal Nanoparticles/ultrastructure , Molecular Sequence Data , Protein Binding , Protein Structure, Secondary , Recombinant Proteins/biosynthesis , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Serum Albumin, Bovine/chemistry , Spectrometry, FluorescenceABSTRACT
The precise synthesis of materials and devices with tailored complex structures and properties is a requisite for the development of the next generation of products based on nanotechnology. Nowadays, the technology for the generation of this type of devices lacks the precision to determine their properties and is accomplished mostly by 'trial and error' experimental approaches. The use of bottom-up approaches that rely on highly specific biomolecular interactions of small and simple components is an attractive approach for the templating of nanoscale elements. In nature, protein assemblies define complex structures and functions. Engineering novel bio-inspired assemblies by exploiting the same rules and interactions that encode the natural diversity is an emerging field that opens the door to create nanostructures with numerous potential applications in synthetic biology and nanotechnology. Self-assembly of biological molecules into defined functional structures has a tremendous potential in nano-patterning and the design of novel materials and functional devices. Molecular self-assembly is a process by which complex 3D structures with specified functions are constructed from simple molecular building blocks. Here we discuss the basis of biomolecular templating, the great potential of repeat proteins as building blocks for biomolecular templating and nano-patterning. In particular, we focus on the designed consensus tetratricopeptide repeats (CTPRs), the control on the assembly of these proteins into higher order structures and their potential as building blocks in order to generate functional nanostructures and materials.
Subject(s)
Biocompatible Materials/chemistry , Models, Molecular , Nanostructures/chemistry , Recombinant Fusion Proteins/chemistry , Repetitive Sequences, Amino Acid , Templates, Genetic , Animals , Biocompatible Materials/metabolism , Consensus Sequence , Gene Library , Humans , Peptide Fragments/chemistry , Peptide Fragments/genetics , Peptide Fragments/metabolism , Peptide Library , Protein Conformation , Protein Engineering , Protein Folding , Protein Stability , Protein Structure, Secondary , Recombinant Fusion Proteins/metabolismABSTRACT
INTRODUCTION: Tumor cells can effectively be killed by heat, e.g. by using magnetic hyperthermia. The main challenge in the field, however, is the generation of therapeutic temperatures selectively in the whole tumor region. We aimed to improve magnetic hyperthermia of breast cancer by using innovative nanoparticles which display a high heating potential and are functionalized with a cell internalization and a chemotherapeutic agent to increase cell death. METHODS: The superparamagnetic iron oxide nanoparticles (MF66) were electrostatically functionalized with either Nucant multivalent pseudopeptide (N6L; MF66-N6L), doxorubicin (DOX; MF66-DOX) or both (MF66-N6LDOX). Their cytotoxic potential was assessed in a breast adenocarcinoma cell line MDA-MB-231. Therapeutic efficacy was analyzed on subcutaneous MDA-MB-231 tumor bearing female athymic nude mice. RESULTS: All nanoparticle variants showed an excellent heating potential around 500 W/g Fe in the alternating magnetic field (AMF, conditions: H=15.4 kA/m, f=435 kHz). We could show a gradual inter- and intracellular release of the ligands, and nanoparticle uptake in cells was increased by the N6L functionalization. MF66-DOX and MF66-N6LDOX in combination with hyperthermia were more cytotoxic to breast cancer cells than the respective free ligands. We observed a substantial tumor growth inhibition (to 40% of the initial tumor volume, complete tumor regression in many cases) after intratumoral injection of the nanoparticles in vivo. The proliferative activity of the remaining tumor tissue was distinctly reduced. CONCLUSION: The therapeutic effects of breast cancer magnetic hyperthermia could be strongly enhanced by the combination of MF66 functionalized with N6L and DOX and magnetic hyperthermia. Our approach combines two ways of tumor cell killing (magnetic hyperthermia and chemotherapy) and represents a straightforward strategy for translation into the clinical practice when injecting nanoparticles intratumorally.
Subject(s)
Antineoplastic Agents/administration & dosage , Breast Neoplasms/pathology , Breast Neoplasms/therapy , Ferric Compounds/chemistry , Hyperthermia, Induced/methods , Metal Nanoparticles/administration & dosage , Metal Nanoparticles/chemistry , Animals , Apoptosis , Breast Neoplasms/diagnosis , Cell Line, Tumor , Disease Models, Animal , Doxorubicin/administration & dosage , Drug Delivery Systems , Drug Liberation , Female , Humans , Hyperthermia, Induced/adverse effects , Metal Nanoparticles/adverse effects , Mice , Mice, Nude , X-Ray Microtomography , Xenograft Model Antitumor AssaysABSTRACT
Photodynamic therapy (PDT) for brain tumors appears to be complementary to conventional treatments. A number of studies show the major role of the vascular effect in the tumor eradication by PDT. For interstitial PDT (iPDT) of brain tumors guided by real-time imaging, multifunctional nanoparticles consisting of a surface-localized tumor vasculature targeting neuropilin-1 (NRP-1) peptide and encapsulated photosensitizer and magnetic resonance imaging (MRI) contrast agents, have been designed. Nanoplatforms confer photosensitivity to cells and demonstrate a molecular affinity to NRP-1. Intravenous injection into rats bearing intracranial glioma exhibited a dynamic contrast-enhanced MRI for angiogenic endothelial cells lining the neovessels mainly located in the peripheral tumor. By using MRI completed by NRP-1 protein expression of the tumor and brain adjacent to tumor tissues, we checked the selectivity of the nanoparticles. This study represents the first in vivo proof of concept of closed-head iPDT guided by real-time MRI using targeted ultrasmall nanoplatforms. From the clinical editor: The authors constructed tumor vascular peptide targeting multifunctional silica-based nanoparticles, with encapsulated gadolinium oxide as MRI contrast agent and chlorin as a photosensitizer, as a proof of concept novel treatment for glioblastoma in an animal model.
Subject(s)
Brain Neoplasms , Glioma , Magnetic Resonance Angiography , Photochemotherapy/methods , Photosensitizing Agents , Animals , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/drug therapy , Cell Line, Tumor , Female , Glioma/diagnostic imaging , Glioma/drug therapy , Humans , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Neuropilin-1/chemistry , Neuropilin-1/therapeutic use , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Radiography , Rats , Rats, NudeABSTRACT
In this study, a general approach for the multifunctionalization of magnetic nanoparticles (MNPs) with drugs (Doxorubicin and Gemcitabine) and targeting moieties (Nucant pseudopeptide) for controlled and selective release is described. The functionalization is achieved by the formation of disulfide bonds between MNPs and drugs derivatives synthesized in this work. Our strategy consists in the introduction of a pyridyldisulfide moiety to the drugs that react efficiently with sulfhydryl groups of pre-activated MNPs. This approach also allows the quantification of the covalently immobilized drug by measuring the amount of the 2-pyridinethione released during the process. The linkers developed here allow the release of drugs without any chemical modification. This process is triggered under highly reducing environment, such as that present inside the cells. Complete release of drugs is achieved within 5-8 h under intracellular conditions whereas negligible percentage of release is observed in extracellular conditions. We propose here a modular general approach for the functionalization of nanoparticles that can be used for different types of drugs and targeting agents.
Subject(s)
Antineoplastic Agents/pharmacology , Deoxycytidine/analogs & derivatives , Doxorubicin/pharmacology , Drug Carriers/chemistry , Drug Delivery Systems , Magnetite Nanoparticles/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Deoxycytidine/chemistry , Deoxycytidine/pharmacology , Dose-Response Relationship, Drug , Doxorubicin/chemistry , Drug Screening Assays, Antitumor , Glycoproteins , Humans , Intercellular Signaling Peptides and Proteins , MCF-7 Cells , Structure-Activity Relationship , GemcitabineABSTRACT
Iron oxide nanoparticles (IONPs) occupy a privileged position among magnetic nanomaterials with potential applications in medicine and biology. They have been widely used in preclinical experiments for imaging contrast enhancement, magnetic resonance, immunoassays, cell tracking, tissue repair, magnetic hyperthermia and drug delivery. Despite these promising results, their successful translation into a clinical setting is strongly dependent upon their physicochemical properties, toxicity and functionalization possibilities. Currently, IONPs-based medical applications are limited to the use of non-functionalized IONPs smaller than 100 nm, with overall narrow particle size distribution, so that the particles have uniform physical and chemical properties. However, the main entry of IONPs into the scene of medical application will surely arise from their functionalization possibilities that will provide them with the capacity to target specific cells within the body, and hence to play a role in the development of specific therapies. In this review, we offer an overview of their basic physicochemical design parameters, giving an account of the progress made in their functionalization and current clinical applications. We place special emphasis on past and present clinical trials.
ABSTRACT
This paper presents energy transfer occurring in small organically modified core-shell nanoparticles (core lanthanide oxide, shell polysiloxane) (diameter < 10 nm) conjugated with photosensitizers designed for photodynamic therapy applications. These nanoparticles covalently encapsulate a photosensitizing PDT drug in different concentrations. Stable dispersions of the nanoparticles were prepared and the photophysical properties of the photosensitizers were studied and compared to those of the photosensitizers in solution. Increasing the photosensitizer concentration in the nanoparticles was not found to cause any changes in the absorption properties while fluorescence and singlet oxygen quantum yields decreased. As a possible explanation, we have suggested that both long distance energy transfer such as FRET and self-quenching could occur into the nanoparticles. A simple "trend" model of this kind of energy transfer complies with results of experiments on steady state fluorescence and singlet oxygen luminescence.
Subject(s)
Nanoparticles/chemistry , Photosensitizing Agents/chemistry , Drug Carriers/chemistry , Energy Transfer , Fluorescence , Fluorescence Resonance Energy Transfer , Humans , Lanthanum/chemistry , Luminescence , Models, Chemical , Neoplasms/drug therapy , Oxides/chemistry , Photochemical Processes , Photochemotherapy/methods , Photosensitizing Agents/administration & dosage , Siloxanes/chemistry , Singlet Oxygen/chemistry , Spectrometry, FluorescenceABSTRACT
AIM: The strategy developed aims to favor the vascular effect of photodynamic therapy by targeting tumor-associated vascularization using peptide-functionalized nanoparticles. We previously described the conjugation of a photosensitizer to a peptide targeting neuropilin-1 overexpressed in tumor angiogenic vessels. MATERIALS & METHODS: In this study, we have designed and photophysically characterized a multifunctional nanoparticle consisting of a surface-localized tumor vasculature targeting peptides and encapsulated photodynamic therapy and imaging agents. RESULTS & CONCLUSION: The elaboration of these multifunctional silica-based nanoparticles is reported. Nanoparticles functionalized with approximately 4.2 peptides bound to recombinant neuropilin-1 protein. Nanoparticles conferred photosensitivity to cells overexpressing neuropilin-1, providing evidence that the chlorin grafted within the nanoparticle matrix can be photoactivated to yield photocytotoxic effects in vitro.
Subject(s)
Nanoparticles/chemistry , Photochemotherapy/methods , Silicon Dioxide/chemistry , Cell Line, Tumor , Cell Survival/drug effects , Humans , Molecular Structure , Neuropilin-1/chemistry , Peptides/chemical synthesis , Peptides/chemistry , Peptides/pharmacology , Photosensitizing Agents/chemical synthesis , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Recombinant Proteins/chemistryABSTRACT
In the present work, we report on the synthesis of cellulose cotton fibers bearing different types of photosensitizers with the aim to prepare new efficient polymeric materials for antimicrobial applications. Anionic, neutral, and cationic amino porphyrins have been covalently grafted on cotton fabric, without previous chemical modification of the cellulosic support, using a 1,3,5-triazine derivative as the linker. The obtained porphyrin-grafted cotton fabrics were characterized by infrared (ATR-FTIR), diffuse reflectance UV-vis (DRUV) spectroscopies, and thermogravimetric analysis (TGA) to confirm the triazine linkage. Antimicrobial activity of porphyrin-cellulose materials was tested under visible light irradiation against Staphylococcus aureus and Escherichia coli . The results showed excellent activity on the Gram-positive bacterium, showing structure-activity relationship, although no photodamage of the Gram-negative microorganism was recorded. A mechanism of bacterial inactivation by photosensitive surfaces is proposed.
Subject(s)
Anti-Bacterial Agents/chemistry , Cotton Fiber , Porphyrins/chemistry , Triazines/chemistry , Light , Microscopy, Electron, Scanning , Spectrophotometry, Ultraviolet , Spectroscopy, Fourier Transform Infrared , ThermogravimetryABSTRACT
The synthesis of silicalites and Mesoporous Silica Nanoparticles (MSN), which covalently incorporate original water-soluble photosensitizers for PDT applications is described. PDT was performed on MDA-MB-231 breast cancer cells. All the nanoparticles showed significant cell death after irradiation, which was not correlated with (1)O(2) quantum yield of the nanoparticles. Other parameters are involved and in particular the surface and shape of the nanoparticles which influence the pathway of endocytosis. Functionalization with mannose was necessary to obtain the best results with PDT due to an active endocytosis of mannose-functionalized nanoparticles. The quantity of mannose on the surface should be carefully adjusted as a too high amount of mannose impairs the phototoxicity of the nanoparticles. Fluorescein was also encapsulated in MCM-41 type MSN in order to localize the nanoparticles in the organelles of the cells by confocal microscopy. The MSN were localized in lysosomes after active endocytosis by mannose receptors.
Subject(s)
Breast Neoplasms/drug therapy , Photochemotherapy/methods , Silicates/chemistry , Silicon Dioxide/chemistry , Breast Neoplasms/pathology , Cell Line, Tumor , Drug Delivery Systems , Endocytosis , Female , Fluorescein/administration & dosage , Fluorescent Dyes/administration & dosage , Humans , Lectins, C-Type/metabolism , Lysosomes/metabolism , Mannose/chemistry , Mannose Receptor , Mannose-Binding Lectins/metabolism , Microscopy, Confocal , Nanoparticles , Receptors, Cell Surface/metabolism , Singlet Oxygen/chemistryABSTRACT
Silica-based nanoparticles for applications in photodynamic therapy (PDT) have emerged as a promising field for the treatment of cancer. In this review, based on the pathway the photosensitizer is entrapped inside the silica matrix, the different methods for the synthesis of silica-based nanoparticles are described from the pioneering works to the latest achievements which concern multifunctional nanoplatforms, up-converting nanoparticles, two-photon PDT, vectorization and in vivo applications.
Subject(s)
Nanoparticles/chemistry , Silicon Dioxide/chemistry , Humans , Nanoparticles/therapeutic use , Neoplasms/diagnosis , Neoplasms/drug therapy , Photochemotherapy , Photosensitizing Agents/chemistry , Photosensitizing Agents/therapeutic use , Reactive Oxygen Species/metabolismABSTRACT
Functionalisation of MSN with mannose for PDT applications dramatically improved the efficiency of PDT on breast cancer cells.
Subject(s)
Mannose/chemistry , Nanoparticles/chemistry , Photochemotherapy , Silicon Dioxide/chemistry , Apoptosis , Cell Line, Tumor , Drug Delivery Systems , HeLa Cells , Humans , Lectins, C-Type/metabolism , Mannose/metabolism , Mannose Receptor , Mannose-Binding Lectins/metabolism , Molecular Structure , Receptors, Cell Surface/metabolismABSTRACT
Photodynamic therapy (PDT) in cancer treatment involves the uptake of a photosensitizer by cancer tissue followed by photoirradiation. The use of nanoparticles as carriers of photosensitizers is a very promising approach because these nanomaterials can satisfy all the requirements for an ideal PDT agent. This review describes and compares the different individual types of nanoparticles that are currently in use for PDT applications. Recent advances in the use of nanoparticles, including inorganic oxide-, metallic-, ceramic-, and biodegradable polymer-based nanomaterials as carriers of photosensitizing agents, are highlighted. We describe the nanoparticles in terms of stability, photocytotoxic efficiency, biodistribution and therapeutic efficiency. Finally, we summarize exciting new results concerning the improvement of the photophysical properties of nanoparticles by means of biphotonic absorption and upconversion.