RESUMEN
Nano-mupirocin is a PEGylated nano-liposomal formulation of the antibiotic mupirocin, undergoing evaluation for treating infectious diseases and intratumor bacteria. Intratumoral microbiota play an important role in the regulation of tumor progression and therapeutic efficacy. However, antibiotic use to target intratumoral bacteria should be performed in a way that will not affect the gut microbiota, found to enable the efficacy of cancer treatments. Nano-mupirocin may offer such a selective treatment. Herein, we demonstrate the ability of Nano-mupirocin to successfully target tumor-residing Fusobacterium nucleatum without an immediate effect on the gut microbiome. In-depth characterization of this novel formulation was performed, and the main findings include: (i). the pharmacokinetic analysis of mupirocin administered as Nano-mupirocin vs mupirocin lithium (free drug) demonstrated that most of the Nano-mupirocin in plasma is liposome associated; (ii). microbiome analysis of rat feces showed no significant short-term difference between Nano-mupirocin, mupirocin lithium and controls; (iii). Nano-mupirocin was active against intratumoral F. nucleatum, a tumor promoting bacteria that accumulates in tumors of the AT3 mice model of breast cancer. These data suggest the ability of Nano-mupirocin to target tumor residing and promoting bacteria.
RESUMEN
Nanotechnology for drug delivery has made significant advancements over the last two decades. Innovations have been made in cancer research and development, including chemotherapies, imaging agents, and vaccine strategies, as well as other therapeutic areas, e.g., the recent commercialization of mRNA lipid nanoparticles as vaccines against the SARS-CoV-2 virus. The field has also seen technological advancements to aid in addressing the complex questions posed by these novel therapies. In this latest edition of protocols and methods for nanoparticle characterization, we highlight both old and new methodologies for defining physicochemical properties, present both in vitro and in vivo methods to test for a variety of immunotoxicities, and describe assays used for pharmacological studies to assess drug release and tissue distribution.
Asunto(s)
Nanopartículas , Vacunas , Nanomedicina/métodos , Nanotecnología/métodos , Sistemas de Liberación de Medicamentos/métodos , Nanopartículas/químicaRESUMEN
The evaluation of temperature-dependent drug release for solubilizing nanoformulations uses a modification of the stable isotope ultrafiltration assay (SITUA). This method is specific to parenterally administered solubilizing nanomedicines and can be used to assess drug release from the total dosage form for regulatory purposes of lot release. The principle upon which this method is based is the relationship between drug solubility and temperature in a plasma simulating media, 4.5% human serum albumin, that allows for discrimination of passing and failing lots based upon the release characteristics.
Asunto(s)
Isótopos , Ultrafiltración , Humanos , Liberación de Fármacos , Temperatura , SolubilidadRESUMEN
A primary issue with nanomedicine biological evaluation is determination of nanoparticle carrier tissue distribution and stability. Here we present a method to evaluate nanomedicine distribution in tissues that is applicable to most nanomedicine constructs. This method utilizes immunohistochemical (IHC) analysis of an Alexa Fluor 488-tag and/or polyethylene glycol (PEG), a very common nanomedicine component, for tissue localization. Using specific Alexa Fluor 488- and/or PEG antibody-based IHC staining procedures allows evaluation of high-resolution nanoparticle tissue distribution, nanoparticle tissue stability, and also allows correlation of distribution with morphological changes. This protocol outlines the methods to follow to ensure proper tissue collection and optimized immunohistochemical staining of Alexa Fluor 488-tag and PEG in tissues.
Asunto(s)
Fluoresceínas , Colorantes Fluorescentes , Polietilenglicoles , Ácidos Sulfónicos , Inmunohistoquímica , Nanomedicina , Distribución TisularRESUMEN
Paclitaxel (PTX) is a frequently prescribed chemotherapy drug used to treat a wide variety of solid tumors. Oligo(lactic acid)8-PTX prodrug (o(LA)8-PTX) loaded poly(ethylene glycol)-b-poly(lactic acid) (PEG-b-PLA) micelles have higher loading, slower release and higher antitumor efficacy in murine tumor models over PTX-loaded PEG-b-PLA micelles. The goal of this work is to study plasma stability of o(LA)8-PTX-loaded PEG-b-PLA micelles and its pharmacokinetics after IV injection in rats. In rat plasma, o(LA)8-PTX prodrug is metabolized into o(LA)1-PTX and PTX. In human plasma, o(LA)8-PTX is metabolized more slowly into o(LA)2-PTX, o(LA)1-PTX, and PTX. After IV injection of 10 mg/kg PTX-equiv of o(LA)8-PTX prodrug loaded PEG-b-PLA micelles in Sprague-Dawley rats, metabolite abundance in plasma follows the order: o(LA)1-PTX > o(LA)2-PTX > o(LA)4-PTX > o(LA)6-PTX. Bile metabolite profiles of the o(LA)8-PTX prodrug is similar to plasma metabolite profiles. In comparison to equivalent doses of Abraxane®, plasma PTX exposure is two orders of magnitude higher for Abraxane® than PTX from o(LA)8-PTX prodrug loaded PEG-b-PLA micelles, and plasma o(LA)1-PTX exposure is fivefold higher than PTX from Abraxane®, demonstrating heightened plasma metabolite exposure for enhanced antitumor efficacy.
Asunto(s)
Paclitaxel , Profármacos , Ratas , Ratones , Humanos , Animales , Paclitaxel/farmacocinética , Ácido Láctico , Micelas , Paclitaxel Unido a Albúmina , Portadores de Fármacos/farmacocinética , Línea Celular Tumoral , Ratas Sprague-Dawley , Polímeros , PoliésteresRESUMEN
The ability of pulsed nature of synchrotron radiation opens up the possibility of studying microsecond dynamics in complex materials via speckle-based techniques. Here, we present the study of measuring the dynamics of a colloidal system by combining single and multiple X-ray pulses of a storage ring. In addition, we apply speckle correlation techniques at various pulse patterns to collect correlation functions from nanoseconds to milliseconds. The obtained sample dynamics from all correlation techniques at different pulse patterns are in very good agreement with the expected dynamics of Brownian motions of silica nanoparticles in water. Our study will pave the way for future pulsed X-ray investigations at various synchrotron X-ray sources using individual X-ray pulse patterns.
RESUMEN
Survival from pancreatic cancer is poor because most cancers are diagnosed in the late stages and there are no therapies to prevent the progression of precancerous pancreatic intraepithelial neoplasms (PanINs). Inhibiting mutant KRASG12D, the primary driver mutation in most human pancreatic cancers, has been challenging. The cholecystokinin-B receptor (CCK-BR) is absent in the normal pancreas but becomes expressed in high grade PanIN lesions and is over-expressed in pancreatic cancer making it a prime target for therapy. We developed a biodegradable nanoparticle polyplex (NP) that binds selectively to the CCK-BR on PanINs and pancreatic cancer to deliver gene therapy. PanIN progression was halted and the pancreas extracellular matrix rendered less carcinogenic in P48-Cre/LSL-KrasG12D/+ mice treated with the CCK-BR targeted NP loaded with siRNA to mutant Kras. The targeted NP also slowed proliferation, decreased metastases and improved survival in mice bearing large orthotopic pancreatic tumors. Safety and toxicity studies were performed in immune competent mice after short or long-term exposure and showed no off-target toxicity by histological or biochemical evaluation. Precision therapy with target-specific NPs provides a novel approach to slow progression of advanced pancreatic cancer and also prevents the development of pancreatic cancer in high-risk subjects without toxicity to other tissues.
Asunto(s)
Carcinoma in Situ , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Ratones , Humanos , Animales , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Modelos Animales de Enfermedad , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/prevención & control , Páncreas/metabolismo , Carcinogénesis/genética , Carcinogénesis/patología , Carcinoma in Situ/genética , Carcinoma Ductal Pancreático/patología , Neoplasias PancreáticasRESUMEN
Cancer nanotechnologies possess immense potential as therapeutic and diagnostic treatment modalities and have undergone significant and rapid advancement in recent years. With this emergence, the complexities of data standards in the field are on the rise. Data sharing and reanalysis is essential to more fully utilize this complex, interdisciplinary information to answer research questions, promote the technologies, optimize use of funding, and maximize the return on scientific investments. In order to support this, various data-sharing portals and repositories have been developed which not only provide searchable nanomaterial characterization data, but also provide access to standardized protocols for synthesis and characterization of nanomaterials as well as cutting-edge publications. The National Cancer Institute's (NCI) caNanoLab is a dedicated repository for all aspects pertaining to cancer-related nanotechnology data. The searchable database provides a unique opportunity for data mining and the use of artificial intelligence and machine learning, which aims to be an essential arm of future research studies, potentially speeding the design and optimization of next-generation therapies. It also provides an opportunity to track the latest trends and patterns in nanomedicine research. This manuscript provides the first look at such trends extracted from caNanoLab and compares these to similar metrics from the NCI's Nanotechnology Characterization Laboratory, a laboratory providing preclinical characterization of cancer nanotechnologies to researchers around the globe. Together, these analyses provide insight into the emerging interests of the research community and rise of promising nanoparticle technologies.
Asunto(s)
Nanoestructuras , Neoplasias , Estados Unidos , Humanos , National Cancer Institute (U.S.) , Inteligencia Artificial , Nanotecnología/métodos , Nanomedicina/métodos , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológicoRESUMEN
The earliest example of in vivo expression of exogenous mRNA is by direct intramuscular injection in mice without the aid of a delivery vehicle. The current state of the art for therapeutic nucleic acid delivery is lipid nanoparticles (LNP), which are composed of cholesterol, a helper lipid, a PEGylated lipid and an ionizable amine-containing lipid. The liver is the primary organ of LNP accumulation following intravenous administration and is also observed to varying degrees following intramuscular and subcutaneous routes. Delivery of nucleic acid to hepatocytes by LNP has therapeutic potential, but there are many disease indications that would benefit from non-hepatic LNP tissue and cell population targeting, such as cancer, and neurological, cardiovascular and infectious diseases. This review will concentrate on the current efforts to develop the next generation of tissue-targeted LNP constructs for therapeutic nucleic acids.
RESUMEN
Survival from pancreatic cancer remains extremely poor, in part because this malignancy is not diagnosed in the early stages, and precancerous pancreatic intraepithelial neoplasia (PanIN) lesions are not seen on routine radiographic imaging. Since the cholecystokinin-B receptor (CCK-BR) becomes over-expressed in PanIN lesions, it may serve as a target for early detection. We developed a biodegradable fluorescent polyplex nanoparticle (NP) that selectively targets the CCK-BR. The NP was complexed to a fluorescent oligonucleotide with Alexa Fluor 647 for far-red imaging and to an oligonucleotide conjugated to Alexa Fluor 488 for localization by immunohistochemistry. Fluorescence was detected over the pancreas of five- to ten-month-old LSL-KrasG12D/+; P48-Cre (KC) mice only after the injection of the receptor target-specific NP and not after injection of untargeted NP. Ex vivo tissue imaging and selective immunohistochemistry confirmed particle localization only to PanIN lesions in the pancreas and not in other organs, supporting the tissue specificity. A human pancreas tissue microarray demonstrated immunoreactivity for the CCK-BR only in the PanIN lesions and not in normal pancreas tissue. The long-term goal would be to develop this imaging tool for screening human subjects at high risk for pancreatic cancer to enable early cancer detection.
Asunto(s)
Fluoresceínas/administración & dosificación , Imagen Óptica/métodos , Neoplasias Pancreáticas/diagnóstico por imagen , Lesiones Precancerosas/diagnóstico por imagen , Receptor de Colecistoquinina B/metabolismo , Ácidos Sulfónicos/administración & dosificación , Animales , Línea Celular Tumoral , Modelos Animales de Enfermedad , Detección Precoz del Cáncer , Femenino , Humanos , Inmunohistoquímica , Masculino , Ratones , Nanopartículas , Especificidad de Órganos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Lesiones Precancerosas/genética , Lesiones Precancerosas/metabolismo , Análisis por Matrices de Proteínas , Proteínas Proto-Oncogénicas p21(ras)/genéticaRESUMEN
The in vivo fate of nanoformulated drugs is governed by the physicochemical properties of the drug and the functionality of nanocarriers. Nanoformulations such as polymeric micelles, which physically encapsulate poorly soluble drugs, release their payload into the bloodstream during systemic circulation. This results in three distinct fractions of the drug-nanomedicine: encapsulated, protein-bound, and free drug. Having a thorough understanding of the pharmacokinetic (PK) profiles of each fraction is essential to elucidate mechanisms of nanomedicine-driven changes in drug exposure and PK/PD relationships pharmacodynamic activity. Here, we present a comprehensive preclinical assessment of the poly (2-oxazoline)-based polymeric micelle of paclitaxel (PTX) (POXOL hl-PM), including bioequivalence comparison to the clinically approved paclitaxel nanomedicine, Abraxane®. Physicochemical characterization and toxicity analysis of POXOL hl-PM was conducted using standardized protocols by the Nanotechnology Characterization Laboratory (NCL). The bioequivalence of POXOL hl-PM to Abraxane® was evaluated in rats and rhesus macaques using the NCL's established stable isotope tracer ultrafiltration assay (SITUA) to delineate the plasma PK of each PTX fraction. The SITUA study revealed that POXOL hl-PM and Abraxane® had comparable PK profiles not only for total PTX but also for the distinct drug fractions, suggesting bioequivalence in given animal models. The comprehensive preclinical evaluation of POXOL hl-PM in this study showcases a series of widely applicable standardized studies by NCL for assessing nanoformulations prior to clinical investigation.
Asunto(s)
Antineoplásicos Fitogénicos , Paclitaxel , Paclitaxel Unido a Albúmina , Animales , Línea Celular Tumoral , Portadores de Fármacos , Isótopos , Macaca mulatta , Micelas , Ratas , Roedores , Equivalencia TerapéuticaRESUMEN
Despite imaging agents being some of the earliest nanomedicines in clinical use, the vast majority of current research and translational activities in the nanomedicine field involves therapeutics, while imaging agents are severely underrepresented. The reasons for this lack of representation are several fold, including difficulties in synthesis and scale-up, biocompatibility issues, lack of suitable tissue/disease selective targeting ligands and receptors, and a high bar for regulatory approval. The recent focus on immunotherapies and personalized medicine, and development of nanoparticle constructs with better tissue distribution and selectivity, provide new opportunities for nanomedicine imaging agent development. This manuscript will provide an overview of trends in imaging nanomedicine characterization and biocompatibility, and new horizons for future development. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine.
Asunto(s)
Diagnóstico por Imagen , Nanopartículas , Nanoestructuras , Biología , Nanomedicina , Medicina de PrecisiónRESUMEN
We have developed a macromolecular prodrug platform based on poly(l-lysine succinylated) (PLS) that targets scavenger receptor A1 (SR-A1), a receptor expressed by myeloid and endothelial cells. We demonstrate the selective uptake of PLS by murine macrophage, RAW 264.7 cells, which was eliminated upon cotreatment with the SR-A inhibitor polyinosinic acid (poly I). Further, we observed no uptake of PLS in an SR-A1-deficient RAW 264.7 cell line, even after 24 h incubation. In mice, PLS distributed to lymphatic organs following i.v. injection, as observed by ex vivo fluorescent imaging, and accumulated in lymph nodes following both i.v. and i.d. administrations, based on immunohistochemical analysis with high-resolution microscopy. As a proof-of-concept, the HIV antiviral emtricitabine (FTC) was conjugated to the polymer's succinyl groups via ester bonds, with a drug loading of 14.2% (wt/wt). The prodrug (PLS-FTC) demonstrated controlled release properties in vitro with a release half-life of 15 h in human plasma and 29 h in esterase-inhibited plasma, indicating that drug release occurs through both enzymatic and nonenzymatic mechanisms. Upon incubation of PLS-FTC with human peripheral blood mononuclear cells (PBMCs), the released drug was converted to the active metabolite FTC triphosphate. In a pharmacokinetic study in rats, the prodrug achieved â¼7-19-fold higher concentrations in lymphatic tissues compared to those in FTC control, supporting lymphatic-targeted drug delivery. We believe that the SR-A1-targeted macromolecular PLS prodrug platform has extraordinary potential for the treatment of infectious diseases.
Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Portadores de Fármacos/química , Infecciones por VIH/tratamiento farmacológico , Receptores Depuradores de Clase A/metabolismo , Animales , Fármacos Anti-VIH/farmacocinética , Liberación de Fármacos , Emtricitabina/administración & dosificación , Emtricitabina/farmacocinética , Femenino , Semivida , Humanos , Masculino , Ratones , Poli I/farmacología , Polilisina/química , Profármacos/administración & dosificación , Profármacos/farmacocinética , Prueba de Estudio Conceptual , Células RAW 264.7 , Ratas , Receptores Depuradores de Clase A/antagonistas & inhibidores , Receptores Depuradores de Clase A/genéticaRESUMEN
Nanoparticle (NP) delivery to solid tumors has recently been questioned. To better understand the magnitude of NP tumor delivery, we reanalyzed published murine NP tumor pharmacokinetic (PK) data used in the Wilhelm et al. study. Studies included in their analysis reporting matched tumor and blood concentration versus time data were evaluated using classical PK endpoints and compared to the unestablished percent injected dose (%ID) in tumor metric from the Wilhelm et al. study. The %ID in tumor was poorly correlated with standard PK metrics that describe NP tumor delivery (AUCtumor/AUCblood ratio) and only moderately associated with maximal tumor concentration. The relative tumor delivery of NPs was ~100-fold greater as assessed by the standard AUCtumor/AUCblood ratio than by %ID in tumor. These results strongly suggest that PK metrics and calculations can influence the interpretation of NP tumor delivery and stress the need to properly validate novel PK metrics against traditional approaches.
RESUMEN
The pharmacokinetics of nanomedicines are complicated by the unique dispositional characteristics of the drug carrier. Most simplistically, the carrier could be a solubilizing platform that allows administration of a hydrophobic drug. Alternatively, the carrier could be stable and release the drug in a controlled manner, allowing for distribution of the carrier to influence distribution of the encapsulated drug. A third potential dispositional mechanism is carriers that are not stably complexed to the drug, but rather bind the drug in a dynamic equilibrium, similar to the binding of unbound drug to protein; since the nanocarrier has distributional and binding characteristics unlike plasma proteins, the equilibrium binding of drug to a nanocarrier can affect pharmacokinetics in unexpected ways, diverging from classical protein binding paradigms. The recently developed stable isotope tracer ultrafiltration assay (SITUA) for nanomedicine fractionation is uniquely suited for distinguishing and comparing these carrier/drug interactions. Here we present the the encapsulated, unencapsulated, and unbound drug fraction pharmacokinetic profiles in rats for marketed nanomedicines, representing examples of controlled release (doxorubicin liposomes, Doxil; and doxorubicin HCl liposome generic), equilibrium binding (paclitaxel cremophor micelle solution, Taxol generic), and solubilizing (paclitaxel albumin nanoparticle, Abraxane; and paclitaxel polylactic acid micelle, Genexol-PM) nanomedicine formulations. The utility of the SITUA method in differentiating these unique pharmacokinetic profiles and its potential for use in establishing generic nanomedicine bioequivalence are discussed.
RESUMEN
We report experimental results on the diffractive imaging of three-dimensionally aligned 2,5-diiodothiophene molecules. The molecules were aligned by chirped near-infrared laser pulses, and their structure was probed at a photon energy of 9.5 keV (λ ≈ 130 pm) provided by the Linac Coherent Light Source. Diffracted photons were recorded on the Cornell-SLAC pixel array detector, and a two-dimensional diffraction pattern of the equilibrium structure of 2,5-diiodothiophene was recorded. The retrieved distance between the two iodine atoms agrees with the quantum-chemically calculated molecular structure to be within 5%. The experimental approach allows for the imaging of intrinsic molecular dynamics in the molecular frame, albeit this requires more experimental data, which should be readily available at upcoming high-repetition-rate facilities.
RESUMEN
The chloroquine family of antimalarials has a long history of use, spanning many decades. Despite this extensive clinical experience, novel applications, including use in autoimmune disorders, infectious disease, and cancer, have only recently been identified. While short term use of chloroquine or hydroxychloroquine is safe at traditional therapeutic doses in patients without predisposing conditions, administration of higher doses and for longer durations are associated with toxicity, including retinotoxicity. Additional liabilities of these medications include pharmacokinetic profiles that require extended dosing to achieve therapeutic tissue concentrations. To improve chloroquine therapy, researchers have turned toward nanomedicine reformulation of chloroquine and hydroxychloroquine to increase exposure of target tissues relative to off-target tissues, thereby improving the therapeutic index. This review highlights these reformulation efforts to date, identifying issues in experimental designs leading to ambiguity regarding the nanoformulation improvements and lack of thorough pharmacokinetics and safety evaluation. Gaps in our current understanding of these formulations, as well as recommendations for future formulation efforts, are presented.
Asunto(s)
Antimaláricos/química , Antimaláricos/farmacología , Cloroquina/química , Enfermedades Transmisibles/tratamiento farmacológico , Composición de Medicamentos/métodos , Hidroxicloroquina/química , Nanomedicina , Animales , HumanosAsunto(s)
Ceramidas/uso terapéutico , Portadores de Fármacos/química , Leucemia Mieloide Aguda/tratamiento farmacológico , Liposomas/química , Esfingolípidos/metabolismo , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/uso terapéutico , Ceramidas/administración & dosificación , Sistemas de Liberación de Medicamentos , Humanos , Leucemia Mieloide Aguda/metabolismo , Nanoestructuras , Resultado del Tratamiento , Vinblastina/farmacología , Vinblastina/uso terapéuticoRESUMEN
The European X-ray Free-Electron Laser (FEL) became the first operational high-repetition-rate hard X-ray FEL with first lasing in May 2017. Biological structure determination has already benefitted from the unique properties and capabilities of X-ray FELs, predominantly through the development and application of serial crystallography. The possibility of now performing such experiments at data rates more than an order of magnitude greater than previous X-ray FELs enables not only a higher rate of discovery but also new classes of experiments previously not feasible at lower data rates. One example is time-resolved experiments requiring a higher number of time steps for interpretation, or structure determination from samples with low hit rates in conventional X-ray FEL serial crystallography. Following first lasing at the European XFEL, initial commissioning and operation occurred at two scientific instruments, one of which is the Single Particles, Clusters and Biomolecules and Serial Femtosecond Crystallography (SPB/SFX) instrument. This instrument provides a photon energy range, focal spot sizes and diagnostic tools necessary for structure determination of biological specimens. The instrumentation explicitly addresses serial crystallography and the developing single particle imaging method as well as other forward-scattering and diffraction techniques. This paper describes the major science cases of SPB/SFX and its initial instrumentation - in particular its optical systems, available sample delivery methods, 2D detectors, supporting optical laser systems and key diagnostic components. The present capabilities of the instrument will be reviewed and a brief outlook of its future capabilities is also described.
RESUMEN
Photosensitizers can be integrated with drug delivery vehicles to develop chemophototherapy agents with antitumor synergy between chemo- and photocomponents. Long-circulating doxorubicin (Dox) in porphyrin-phospholipid (PoP) liposomes (LC-Dox-PoP) incorporates a phospholipid-like photosensitizer (2 mole %) in the bilayer of Dox-loaded stealth liposomes. Hematological effects of endotoxin-minimized LC-Dox-PoP were characterized via standardized assays. In vitro interaction with erythrocytes, platelets, and plasma coagulation cascade were generally unremarkable, whereas complement activation was found to be similar to that of commercial Doxil. Blood partitioning suggested that both the Dox and PoP components of LC-Dox-PoP were stably entrapped or incorporated in liposomes. This was further confirmed with pharmacokinetic studies in Fischer rats, which showed the PoP and Dox components of the liposomes both had nearly identical, long circulation half-lives (25-26 hours). In a large orthotopic mammary tumor model in Fischer rats, following intravenous dosing (2 mg/kg Dox), the depth of enhanced Dox delivery in response to 665 nm laser irradiation was over 1 cm. LC-Dox-PoP with laser treatment cured or potently suppressed tumor growth, with greater efficacy observed in tumors 0.8 to 1.2 cm, compared with larger ones. The skin at the treatment site healed within approximately 30 days. Taken together, these data provide insight into nanocharacterization and photo-ablation parameters for a chemophototherapy agent.