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1.  Mix to Validate: A Facile, Reversible PEGylation for Fast Screening of Potential Therapeutic Proteins, TRAIL, In Vivo** 
Mix to Validate: To advance the rate of novel protein therapies entering the clinic, we provide researchers a facile tool for protein drug efficacy testing in animal models in a high throughput manner. Here, we utilize the concept of PEGylating proteins through complementary interactions between His-tag and Ni2+ complex of NTA, a well-established practice in protein research, to improve blood half-life of therapeutic protein candidates after systemic administration in vivo.
PMCID: PMC3902477  PMID: 23740787
Histidine tag; in vivo drug screening; pegylation; protein delivery; protein modification
2.  Mesenchymal stem cell-based cell engineering with multifunctional mesoporous silica nanoparticles for tumor delivery 
Biomaterials  2012;34(7):1772-1780.
Stem cell engineering, the manipulation and control of cells, harnesses tremendous potential for diagnosis and therapy of disease; however, it is still challenging to impart multifunctionalization onto stem cells to achieve both. Here we describe a mesenchymal stem cell (MSC)-based multifunctional platform to target orthotopic glioblastoma by integrating the tumor targeted delivery of mesenchymal stem cells and the multimodal imaging advantage of mesoporous silica nanoparticles (MSNs). Rapid cellular uptake, long retention time and stability of particles exemplify the potential that the combination of MSNs and MSCs has as a stem cell-based multifunctional platform. Using such a platform, we verified tumor-targeted delivery of MSCs by in vivo multimodal imaging in an orthotopic U87MG glioblastoma model, displaying higher tumor uptake than particles without MSCs. As a proof-of-concept, this MSC platform opens a new vision for multifunctional applications of cell products by combining the superiority of stem cells and nanoparticles for actively targeted delivery.
PMCID: PMC3538138  PMID: 23228423
Mesenchymal stem cells (MSCs); mesoporous silica nanoparticles (MSNs); cell engineering; multimodal imaging; targeted delivery
3.  Real-time monitoring of caspase cascade activation in living cells 
We introduce a simple, versatile and robust one-step technique that enables real-time imaging of multiple intracellular caspase activities in living cells without the need for complicated synthetic protocols. Conventional fluorogenic probes or recently reported activatable probes have been designed to target various proteases but are limited to extracellular molecules. Only a few have been applied to image intracellular proteases in living cells because most of these probes have limited cell-permeability. Our platform does not need complicated synthetic processes; instead it involves a straightforward peptide synthesis and a simple mixing step with a commercial transfection agent. The transfection agent efficiently delivered the highly quenched fluorogenic probes, comprised of distinctive pairs of dyes and quenchers, to the initiator caspase-8 and the effector caspase-3 in MDA-MB-435 cells, allowing dual-imaging of the activities of both caspases during the apoptotic process induced by TNF-related apoptosis induced ligand (TRAIL). With the combination of multiple fluorogenic probes, this simple platform can be applied to multiplexed imaging of selected intracellular proteases to study apoptotic processes in pathologies or for cell-based high throughput screening systems for drug discovery.
PMCID: PMC3462246  PMID: 22664474
caspase; activatable probe; fluorescence imaging; peptide; transfection agent
4.  N-Alkyl-PEI Functional Iron Oxide Nanocluster for Efficient siRNA Delivery** 
Small interfering RNA (siRNA) is an emerging class of therapeutics, working by regulating the expression of a specific gene involved in disease progression. Despite the promises, effective transport of siRNA with minimal side effects remains a challenge. In this study, a non-viral nanoparticle gene carrier has been developed and its efficiency for siRNA delivery and transfection has been validated at both in vitro and in vivo levels. Such a nanocarrier, abbreviated as Alkyl-PEI2k-IO, was constructed with a core of iron oxide (IO) and a shell of alkylated PEI2000 (Alkyl-PEI2k). It was found to be able to bind with siRNA, resulting in well-dispersed nanoparticles with a controlled clustering structure and narrow size distribution. Electrophoresis studies showed that the Alkyl-PEI2k-IOs could retard siRNA completely at N/P ratios above 10, protect siRNA from enzymatic degradation in serum and release complexed siRNA efficiently in the presence of polyanionic heparin. The knockdown efficiency of the siRNA loaded nanocarriers was assessed with 4T1 cells stably expressing luciferase (fluc-4T1) and further, with a fluc-4T1 xenograft model. Significant downregulation of luciferase was observed, and unlike the high molecular weight analogs, the Alkyl-PEI2k coated IOs showed a good biocompatibility. In conclusion, Alkyl-PEI2k-IOs demonstrate highly efficient delivery of siRNA and an innocuous toxic profile, making it a potential carrier for gene therapy.
PMCID: PMC3759164  PMID: 21861295
Biomaterials; Superparamagnetic nanoparticles; Polytehyleneimine; Small interfering RNA
5.  Long-term multimodal imaging of tumor draining sentinel lymph nodes using mesoporous silica-based nanoprobes 
Biomaterials  2012;33(17):4370-4378.
The imaging of sentinel lymph nodes (SLNs), the first defense against primary tumor metastasis, has been considered as an important strategy for noninvasive tracking tumor metastasis in clinics. In this study, we report the development and application of mesoporous silica-based triple-modal nanoprobes that integrate multiple functional moieties to facilitate near-infrared optical, magnetic resonance (MR) and positron emission tomography (PET) imaging. After embedding near-infrared dye ZW800, the nanoprobe was labeled with T1 contrast agent Gd3+ and radionuclide 64Cu through chelating reactions. High stability and long intracellular retention time of the nanoprobes was confirmed by in vitro characterization, which facilitate long-term in vivo imaging. Longitudinal multimodal imaging was subsequently achieved to visualize tumor draining SLNs up to 3 weeks in a 4T1 tumor metastatic model. Obvious differences in uptake rate, amount of particles, and contrast between metastatic and contralateral sentinel lymph nodes were observed. These findings provide very helpful guidance for the design of robust multifunctional nanomaterials in SLNs’ mapping and tumor metastasis diagnosis.
PMCID: PMC3758914  PMID: 22425023
Mesoporous silica nanoparticles; Multimodality imaging; Tumor metastasis; Magnetic resonance imaging; Positron emission tomography; Near-infrared fluorescence imaging
6.  A Facile, One-Step Nanocarbon Functionalization for Biomedical Applications 
Nano Letters  2012;12(7):3613-3620.
Despite their immense potential in biomedicine, carbon nanomaterials suffer from inefficient dispersion and biological activity in vivo. Here we utilize a single, yet multifunctional, hyaluronic acid-based biosurfactant to simultaneously disperse nanocarbons and target single-walled carbon nanotubes (SWCNTs) to CD44 receptor positive tumor cells with prompt uptake. Cellular uptake was monitored by intracellular enzyme-activated fluorescence and localization of SWCNTs within cells was further confirmed by Raman mapping. In vivo photoacoustic, fluorescence and positron emission tomography imaging of coated SWCNTs display high tumor targeting capability while providing long-term, fluorescence molecular imaging of targeted enzyme events. By utilizing a single biomaterial surfactant for SWCNT dispersion without additional bioconjugation, we designed a facile technique that brings nanocarbons closer to their biomedical potential.
PMCID: PMC3405986  PMID: 22694219
Carbon nanomaterials; one-step functionalization; hyaluronic acid; nanotubes; molecular
7.  Noninvasive monitoring of orthotopic glioblastoma therapy response using RGD-conjugated iron oxide nanoparticles 
Biomaterials  2012;33(21):5414-5422.
Noninvasive imaging techniques have been considered important strategies in the clinic to monitor tumor early response to therapy. In the present study, we applied RGD peptides conjugated to iron oxide nanoparticles (IONP-RGD) as contrast agents in magnetic resonance imaging (MRI) to noninvasively monitor the response of a vascular disrupting agent VEGF121/rGel in an orthotopic glioblastoma model. RGD peptides were firstly coupled to IONPs coated with a crosslinked PEGylated amphiphilic triblock copolymer. In vitro binding assays confirmed that cellular uptake of particles was mainly dependent on the interaction between RGD and integrin αvβ3 of human umbilical vein endothelial cells (HUVEC). The tumor targeting of IONP-RGD was observed in an orthotopic U87 glioblastoma model. Finally, noninvasive monitoring of the tumor response to VEGF121/rGel therapy at early stages of treatment was successfully accomplished using IONP-RGD as a contrast agent for MRI, a superior method over common anatomical approaches which are based on tumor size measurements. This preclinical study can accelerate anticancer drug development and promote clinical translation of nanoprobes.
PMCID: PMC3577933  PMID: 22560667
Magnetic resonance imaging (MRI); Iron oxide nanoparticles (IONPs); RGD peptides; Tumor targeting; Therapy response
8.  Nanotheranostics for personalized medicine 
Nanotheranostics, the integration of diagnostic and therapeutic function in one system using the benefits of nanotechnology, is extremely attractive for personalized medicine. Because treating cancer is not a one-size-fits-all scenario, it requires therapy to be adapted to the patient’s specific biomolecules. Personalized and precision medicine (PM) does just that. It identifies biomarkers to gain an understanding of the diagnosis and in turn treating the specific disorder based on the precise diagnosis. By predominantly utilizing the unique properties of nanoparticles to achieve biomarker identification and drug delivery, nanotheranostics can be applied to noninvasively discover and target image biomarkers and further deliver treatment based on the biomarker distribution. This is a large and hopeful role theranostics must fill. However, as described in this expert opinion, current nanotechnology-based theranostics systems engineered for PM applications are not yet sufficient. PM is an ever-growing field that will be a driving force for future discoveries in biomedicine, especially cancer theranostics. In this article, the authors dissect the requirements for successful nanotheranostics-based PM.
PMCID: PMC3696508  PMID: 23570404
chemotherapy; drug delivery; molecular imaging; molecular profiling; nanotechnology; nanotheranostics; prodrugs
9.  Nuclear Mapping of Nano-Drug Delivery Systems in Dynamic Cellular Environments 
ACS Nano  2012;6(6):4966-4972.
Nanoformulations have shown great promise for delivering chemotherapeutics and hold tremendous clinical relevance. However nuclear mapping of the chemo drugs is important to predict the success of the nanoformulation. Herein in this study fluorescence microscopy and a subcellular tracking algorithm were used to map the diffusion of chemotherapeutic drugs in cancer cells. Positively charged nanoparticles efficiently carried the chemo drug across the cell membrane. The algorithm helped map free drug and drug loaded nanoparticles, revealing varying nuclear diffusion pattern of the chemotherapeutics in drug-sensitive and resistant cells in a live dynamic cellular environment. While the drug-sensitive cells showed an exponential uptake of the drug with time, resistant cells showed random and asymmetric drug distribution. Moreover nanoparticles carrying the drug remained in the perinuclear region while the drug got accumulated in the cell nuclei. The tracking approach has enabled us to predict the therapeutic success of different nanoscale formulations of doxorubicin.
PMCID: PMC3383922  PMID: 22540867
iron oxide nanoparticles; doxorubicin; drug resistance; computational; nuclear mapping; live cell imaging; cancer
10.  Non-Invasive Monitoring of Pulmonary Fibrosis by Targeting Matrix Metalloproteinases (MMPs) 
Molecular pharmaceutics  2013;10(6):2237-2247.
While idiopathic pulmonary fibrosis (PF) is a devastating lung disease, the management of PF including effective monitoring of disease progression remains a challenge. Herein, we introduce a novel, fast and ultra-sensitive metalloproteinase (MMP) activatable optical probe, named MMP-P12, to non-invasively monitor PF progression and response to PF treatment. A bleomycin (BLM)-induced mouse PF model was subjected non-invasively to optical imaging at various time points after BLM treatment. Mouse PF model developed fibrosis during 21 days of experimental period, and the progression of PF was well correlated with the step-wise increase of MMP-2 expression as examined by quantitative RT-PCR and western blot analysis on the 7-, 14-and 21-day post-BLM administration. On these days, MMP-activated fluorescence images were acquired in vivo and ex vivo. Signal quantification showed time-dependent lung-specific incremental increases in fluorescence signals. As a treatment for PF, secretoglobin 3A2 was daily administered intravenously for five days starting day seven of BLM administration, which resulted in reduced MMP-2 activity and reduction of PF as previously demonstrated. Importantly, the fluorescence signal that reflected MMP activity also decreased in intensity. In conclusion, MMPs may play an important role in PF development and MMP-P12 probe could be a promising tool for PF detection, even at an early stage of the disease as well as an indicator of therapy response.
PMCID: PMC3672268  PMID: 23607644
Pulmonary fibrosis; Matrix metalloproteinase; Optical imaging; Activatable probe; Secretoglobin 3A2
11.  The design and application of fluorophore–gold nanoparticle activatable probes 
Fluorescence-based assays and detection techniques are among the most highly sensitive and popular biological tests for researchers. To match the needs of research and the clinic, detection limits and specificities need to improve, however. One mechanism is to decrease non-specific background signals, which is most efficiently done by increasing fluorescence quenching abilities. Reports in the literature of theoretical and experimental work have shown that metallic gold surfaces and nanoparticles are ultra-efficient fluorescence quenchers. Based on these findings, subsequent reports have described gold nanoparticle fluorescence-based activatable probes that were designed to increase fluorescence intensity based on a range of stimuli. In this way, these probes can detect and signify assorted biomarkers and changes in environmental conditions. In this review, we explore the various factors and theoretical models that affect gold nanoparticle fluorescence quenching, explore current uses of activatable probes, and propose an engineering approach for future development of fluorescence based gold nanoparticle activatable probes.
PMCID: PMC3632443  PMID: 21380462
12.  High-sensitivity nanosensors for biomarker detection† 
Chemical Society reviews  2011;41(7):2641-2655.
High sensitivity nanosensors utilize optical, mechanical, electrical, and magnetic relaxation properties to push detection limits of biomarkers below previously possible concentrations. The unique properties of nanomaterials and nanotechnology are exploited to design biomarker diagnostics. High-sensitivity recognition is achieved by signal and target amplification along with thorough pre-processing of samples. In this tutorial review, we introduce the type of detection signals read by nanosensors to detect extremely small concentrations of biomarkers and provide distinctive examples of high-sensitivity sensors. The use of such high-sensitivity nanosensors can offer earlier detection of disease than currently available to patients and create significant improvements in clinical outcomes.
PMCID: PMC3629948  PMID: 22187721
13.  Inorganic Nanoparticles for Multimodal Molecular Imaging 
Molecular imaging  2011;10(1):3-16.
Multimodal molecular imaging can offer a synergistic improvement of diagnostic ability over a single imaging modality. Recent development of hybrid imaging systems has profoundly impacted the pool of available multimodal imaging probes. In particular, much interest has been focused on biocompatible, inorganic nanoparticle–based multimodal probes. Inorganic nanoparticles offer exceptional advantages to the field of multimodal imaging owing to their unique characteristics, such as nanometer dimensions, tunable imaging properties, and multifunctionality. Nanoparticles mainly based on iron oxide, quantum dots, gold, and silica have been applied to various imaging modalities to characterize and image specific biologic processes on a molecular level. A combination of nanoparticles and other materials such as biomolecules, polymers, and radiometals continue to increase functionality for in vivo multimodal imaging and therapeutic agents. In this review, we discuss the unique concepts, characteristics, and applications of the various multimodal imaging probes based on inorganic nanoparticles.
PMCID: PMC3629957  PMID: 21303611
14.  PEG-transferrin conjugated TRAIL (TNF-related apoptosis-inducing ligand) for therapeutic tumor targeting 
Transferrin (Tf) is considered an effective tumor-targeting agent, and PEGylation effectively prolongs in vivo pharmacokinetics by delaying excretion via the renal route. The authors describe the active tumor targeting of long-acting Tf–PEG–TNF-related apoptosis-inducing ligand conjugate (Tf–PEG–TRAIL) for effective cancer therapy. Tf–PEG–TRAIL was prepared using a two-step N-terminal specific PEGylation procedure using different PEGs (Mw: 3.4, 5, 10 kDa). Eventually, only 10 kDa PEG was linked to Tf and TRAIL because TRAIL (66 kDa) and Tf (81 kDa) were too large to link to 3.4 and 5 kDa PEG. The final conjugate Tf–PEG10K–TRAIL was successfully purified and characterized by SDS-PAGE, western blotting. To determine the specific binding of Tf–PEG10K–TRAIL to Tf receptor, competitive receptor binding assays were performed on K 562 cells. The results obtained demonstrate that the affinity of Tf–PEG10K–TRAIL for Tf receptor is similar to that of native Tf. In contrast, PEG10K–TRAIL demonstrated no specificity. Biodistribution patterns and antitumor effects were investigated in C57BL6 mice bearing B16F10 murine melanomas and BALB/c athymic mice bearing HCT116. Tumor accumulation of Tf–PEG10K–TRAIL was 5.2 fold higher (at 2 h) than TRAIL, because Tf–PEG10K–TRAIL has both passive and active tumor targeting ability. Furthermore, the suppression of tumors by Tf–PEG10K–TRAIL was 3.6 and 1.5 fold those of TRAIL and PEG10K–TRAIL, respectively. These results suggest that Tf–PEG10K–TRAIL is a superior pharmacokinetic conjugate that potently targets tumors and that it should be viewed as a potential cancer therapy.
PMCID: PMC3629958  PMID: 22824780
TRAIL; Transferrin; PEGylation; Passive tumor targeting; Active tumor targeting
15.  Theranostic nanoplatforms for simultaneous cancer imaging and therapy: current approaches and future perspectives 
Nanoscale  2011;4(2):330-342.
Theranostics is a concept which refers to the integration of imaging and therapy. As an evolving new field, it is related to but different from traditional imaging and therapeutics. It embraces multiple techniques to arrive at a comprehensive diagnostic, in vivo molecular images and an individualized treatment regimen. More recently, there is a trend of tangling these efforts with emerging materials and nanotechnologies, in an attempt to develop novel platforms and methodologies to tackle practical issues in clinics. In this article, topics of rationally designed nanoparticles for the simultaneous imaging and therapy of cancer will be discussed. Several exemplary nanoparticle platforms such as polymeric nanoparticles, gold nanomaterials, carbon nanotubes, magnetic nanoparticles and silica nanoparticles will be elaborated on and future challenges of nanoparticle-based systems will be discussed.
PMCID: PMC3629960  PMID: 22134683
16.  HSA coated MnO nanoparticles with prominent MRI contrast for tumor imaging† 
We report in this Communication a facile, two-step surface modification strategy to achieve manganese oxide nanoparticles with prominent MRI T1 contrast. In a U87MG glioblastoma xenograft model, we confirmed that the particles can accumulate efficiently in tumor area to induce effective T1 signal alteration.
PMCID: PMC3629962  PMID: 20730157
17.  Improved Antitumor Activity and Tumor Targeting of NH2-Terminal–Specific PEGylated Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand 
Molecular cancer therapeutics  2010;9(6):1719-1729.
Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) is considered an attractive anticancer agent due to its tumor cell–specific cytotoxicity. However, its low stability, solubility, unexpected side effects, and weak pharmacokinetic profiles restrict its successful clinical application. To develop efficient TRAIL-based anticancer biotherapeutics, a new version of trimeric TRAIL was constructed by incorporating trimer-forming zipper sequences (HZ-TRAIL), and then NH2-terminal–specific PEGylation was done to produce PEGylated TRAIL (PEG-HZ-TRAIL). The biological, physicochemical, and pharmaceutical characteristics of PEG-HZ-TRAIL were then investigated using various in vitro and in vivo experiments, including a cell-based cytotoxicity test, a solubility test, pharmacokinetic analysis, and antitumor efficacy evaluations. Although slight activity loss occurred after PEGylation, PEG-HZ-TRAIL showed excellent tumor cell–specific cytotoxic effects via apoptotic pathways with negligible normal cell toxicity. The stability and pharmacokinetic problems of HZ-TRAIL were successfully overcome by PEGylation. Furthermore, in vivo antitumor tests revealed that PEG-HZ-TRAIL treatment enhanced therapeutic potentials compared with HZ-TRAIL in tumor xenograft animal models, and these enhancements were attributed to its better pharmacokinetic properties and tumor-targeting performance. These findings show that PEG-HZ-TRAIL administration provides an effective antitumor treatment, which exhibits superior tumor targeting and better inhibits tumor growth, and suggest that PEG-HZ-TRAIL should be considered a potential candidate for antitumor biotherapy.
PMCID: PMC3629964  PMID: 20515949
18.  Design and Fabrication of N-Alkyl-Polyethylenimine-Stabilized Iron Oxide Nanoclusters for Gene Delivery 
Methods in enzymology  2012;509:263-276.
With the rapid development of nanotechnology, inorganic magnetic nanoparticles, especially iron oxide nanoparticles (IOs), have emerged as great vehicles for biomedical diagnostic and therapeutic applications. In order to rationally design IO-based gene delivery nanovectors, surface modification is essential and determines the loading and release of the gene of interest. Here we highlight the basic concepts and applications of nonviral gene delivery vehicles based on low molecular weight N-alkyl polyethylenimine-stabilized IOs. The experimental protocols related to these topics are described in this chapter.
PMCID: PMC3629967  PMID: 22568910
19.  Selective Imaging of Mitochondrial Surfaces with Novel Fluorescent Probes 
PMCID: PMC3629968  PMID: 21793151
bioconversions; fluorescent probes; high-throughput screening; mitochondria; organelles
20.  Hybrid Ferritin Nanoparticles as Activatable Probes for Tumor Imaging** 
PMCID: PMC3629976  PMID: 21308906
ferritin; fluorescent probes; imaging agents; metalloenzymes; nanoparticles
21.  Activatable Molecular Probes for Cancer Imaging 
Current topics in medicinal chemistry  2010;10(11):1135-1144.
The development of highly sensitive and specific molecular probes for cancer imaging still remains a daunting challenge. Recently, interdisciplinary research at the interface of imaging sciences and bionanoconjugation chemistry has generated novel activatable imaging probes that can provide high-resolution imaging with ultra-low background signals. Activatable imaging probes are designed to amplify output imaging signals in response to specific biomolecular recognition or environmental changes in real time. This review introduces and highlights the unique design strategies and applications of various activatable imaging probes in cancer imaging.
PMCID: PMC3629980  PMID: 20388112
22.  Multiplex Imaging of an Intracellular Proteolytic Cascade by using a Broad-Spectrum Nanoquencher** 
PMCID: PMC3622558  PMID: 22213412
caspases; fluorescence; imaging agents; nanoparticles; proteolysis
24.  Polymeric Nanoparticle-Based Activatable Near-Infrared Nanosensor for Protease Determination In Vivo 
Nano letters  2009;9(12):4412-4416.
We report here a new protease activatable strategy based on a polymer nanoparticle platform. This nanosensor delivers chemically labeled matrix metalloproteinase (MMP)-activatable fluorogenic peptides to the specific MMPs of interest in vivo. Intravenous administration of the nanosensor in an MMP-positive SCC-7 xenograft tumor and a colon cancer mouse model verified the enzyme specificity of the nanosensor in vivo. The design platform of the nanosensor is flexible and can be fine-tuned for a wide array of applications such as the detection of biomarkers, early diagnosis of disease, and monitoring therapeutic efficacy.
PMCID: PMC3618996  PMID: 19842672
25.  Theranostic nanoparticles based on PEGylated hyaluronic acid for the diagnosis, therapy and monitoring of colon cancer 
Biomaterials  2012;33(26):6186-6193.
Colon cancer is the second leading cause of cancer-related death in the United States. The considerable mortality from colon cancer is due to metastasis to other organs, mainly the liver. In the management of colon cancer, early detection and targeted therapy are crucial. In this study, we aimed to establish a versatile theranostic system for early tumor detection and targeted tumor therapy by using poly(ethylene glycol)-conjugated hyaluronic acid nanoparticles (P-HA-NPs) which can selectively accumulate in tumor tissue. For the diagnostic application, a near-infrared fluorescence (NIRF) imaging dye (Cy 5.5) was chemically conjugated onto the HA backbone of P-HA-NPs. After intravenous injection of Cy5.5-P-HA-NPs into the tumor-bearing mice, small-sized colon tumors as well as liver-implanted colon tumors were effectively visualized using the NIRF imaging technique. For targeted therapy, we physically encapsulated the anticancer drug, irinotecan (IRT), into the hydrophobic cores of P-HA-NPs. Owing to their notable tumor targeting capability, IRT-P-HA-NPs exhibited an excellent antitumor activity while showing a reduction in undesirable systemic toxicity. Importantly, we demonstrated the theranostic application using Cy5.5-P-HA-NPs and IRT-P-HA-NPs in orthotopic colon cancer models. Following the systemic administration of Cy5.5-P-HA-NPs, neoplasia was clearly visualized, and the tumor growth was effectively suppressed by intravenous injection of IRT-P-HA-NPs. It should be emphasized that the therapeutic responses could be simultaneously monitored by Cy5.5-P-HA-NPs. Our results suggest that P-HA-NPs can be used as a versatile theranostic system for the early detection, targeted therapy, and therapeutic monitoring of colon cancer.
PMCID: PMC3617484  PMID: 22687759
Hyaluronic acid; nanoparticle; theranostics; irinotecan; colon cancer; tumor targeting

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