Nanoparticle-based targeted drug delivery

Carbon nanotubes exhibit many unique intrinsic physical and chemical properties and have been intensively explored for biological and biomedical applications in the past few years. In this comprehensive review, we summarize the main results from our and other groups in this field and clarify that surface functionalization is critical to the behavior of carbon nanotubes in biological systems. Ultrasensitive detection of biological species with carbon nanotubes can be realized after surface passivation to inhibit the non-specific binding of biomolecules on the hydrophobic nanotube surface. Electrical nanosensors based on nanotubes provide a label-free approach to biological detection. Surface-enhanced Raman spectroscopy of carbon nanotubes opens up a method of protein microarray with detection sensitivity down to 1 fmol/L. In vitro and in vivo toxicity studies reveal that highly water soluble and serum stable nanotubes are biocompatible, nontoxic, and potentially useful for biomedical applications. In vivo biodistributions vary with the functionalization and possibly also size of nanotubes, with a tendency to accumulate in the reticuloendothelial system (RES), including the liver and spleen, after intravenous administration. If well functionalized, nanotubes may be excreted mainly through the biliary pathway in feces. Carbon nanotube-based drug delivery has shown promise in various In vitro and in vivo experiments including delivery of small interfering RNA (siRNA), paclitaxel and doxorubicin. Moreover, single-walled carbon nanotubes with various interesting intrinsic optical properties have been used as novel photoluminescence, Raman, and photoacoustic contrast agents for imaging of cells and animals. Further multidisciplinary explorations in this field may bring new opportunities in the realm of biomedicine.

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Carbon Nanotubes in Biology and Medicine: In vitro and in vivo Detection, Imaging and Drug Delivery

Chemically functionalized single-walled carbon nanotubes (SWNT) have shown promise in tumor-targeted accumulation in mice and exhibit biocompatibility, excretion, and little toxicity. Here, we show in vivo SWNT drug delivery for tumor suppression in mice. We conjugate paclitaxel (PTX), a widely used cancer chemotherapy drug, to branched polyethylene glycol chains on SWNTs via a cleavable ester bond to obtain a water-soluble SWNT-PTX conjugate. SWNT-PTX affords higher efficacy in suppressing tumor growth than clinical Taxol in a murine 4T1 breast cancer model, owing to prolonged blood circulation and 10-fold higher tumor PTX uptake by SWNT delivery likely through enhanced permeability and retention. Drug molecules carried into the reticuloendothelial system are released from SWNTs and excreted via biliary pathway without causing obvious toxic effects to normal organs. Thus, nanotube drug delivery is promising for high treatment efficacy and minimum side effects for future cancer therapy with low drug doses.

https://cancerres.aacrjournals.org/content/canres/68/16/6652.full.pdf

Drug delivery with carbon nanotubes for in vivo cancer treatment.

Although conventional chemotherapy has been successful to some extent, the main drawbacks of chemotherapy are its poor bioavailability, high-dose requirements, adverse side effects, low therapeutic indices, development of multiple drug resistance, and non-specific targeting. The main aim in the development of drug delivery vehicles is to successfully address these delivery-related problems and carry drugs to the desired sites of therapeutic action while reducing adverse side effects. In this review, we will discuss the different types of materials used as delivery vehicles for chemotherapeutic agents and their structural characteristics that improve the therapeutic efficacy of their drugs and will describe recent scientific advances in the area of chemotherapy, emphasizing challenges in cancer treatments.

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Controlled drug delivery vehicles for cancer treatment and their performance.

https://digital.csic.es/bitstream/10261/134282/5/ADVANCED%20TARGETED.pdf

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy.

Single-walled carbon nanotubes (CNT) are mechanically robust graphene cylinders with a high aspect ratio that are comprised of sp2-bonded carbon atoms and possessing highly regular structures with defined periodicity. CNT exhibit unique mechanochemical properties that can be exploited for the development of novel drug delivery platforms. We hypothesized that novel prototype nanostructures consisting of biologics, radionuclides, fluorochromes, and CNT could be synthesized and designed to target tumor cells. Methods: Tumor-targeting CNT constructs were synthesized from sidewall-functionalized, water-soluble CNT platforms by covalently attaching multiple copies of tumor-specific monoclonal antibodies, radiometal-ion chelates, and fluorescent probes. The constructs were characterized spectroscopically, chromatographically, and electrophoretically. The specific reactivity of these constructs was evaluated in vitro by flow cytometry and cell-based immunoreactivity assays and in vivo using biodistribution in a murine xenograft model of lymphoma. Results: A soluble, reactive CNT platform was used as the starting point to build multifunctional constructs with appended antibody, metal-ion chelate, and fluorescent chromophore moieties to effect specific targeting, to carry and deliver a radiometal-ion, and to report location, respectively. These nanoconstructs were found to be specifically reactive with the human cancer cells they were designed to target in vivo in a model of disseminated human lymphoma and in vitro by flow cytometry and cell-based immunoreactivity assays versus appropriate controls. Conclusion: The key achievement in these studies was the selective targeting of tumor in vitro and in vivo by the use of specific antibodies appended to a soluble, nanoscale CNT construct. The ability to specifically target tumor with prototype-radiolabeled or fluorescent-labeled, antibody-appended CNT constructs was encouraging and suggested further investigation of CNT as a novel delivery platform.

https://jnm.snmjournals.org/content/jnumed/48/7/1180.full.pdf

Tumor Targeting with Antibody-Functionalized, Radiolabeled Carbon Nanotubes

Nanobiohybrids as delivery vehicles for camptothecin.

Calvarial lesions are often asymptomatic and are usually discovered incidentally during computed tomography or magnetic resonance imaging of the brain Calvarial lesions can be benign or malignant Although the majority of skull lesions are benign, it is important to be familiar with their imaging characteristics and to recognise those with malignant features where more aggressive management is needed Clinical information such as the age of the patient, as well as the patient’s history is fundamental in making the correct diagnosis In this article, we will review the imaging features of both common and uncommon calvarial lesions, as well as mimics of these lesions found in clinical practice • Skull lesions are usually discovered incidentally; they can be benign or malignant
 • Metastases are the most frequent cause of skull lesions
 • Metastatic lesions are most commonly due to breast cancer in adults and neuroblastoma in children
 • Multiple myeloma presents as the classic “punched out” lytic lesions on radiographs
 • Eosinophilic granuloma is an osteolytic lesion with bevelled edges

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Radiological review of skull lesions

Purpose To quantify cumulative radiation exposure in patients undergoing arthroscopic hip preservation surgery and occupational exposure to operating room (OR) personnel during such surgery; a secondary objective of this study was to identify factors affecting radiation exposure in patients undergoing hip arthroscopy. Methods Radiation exposure from all preoperative and intraoperative imaging studies was determined for 52 patients undergoing hip arthroscopy. Cumulative and effective radiation doses were calculated and correlated with pathology and body mass index (BMI). Badge dosimeters were worn by OR personnel to measure cumulative occupational exposure. A highly sensitive portable ion chamber was used to evaluate the radiation scatter during surgery performed on a high-BMI patient and a low-BMI patient to reflect a "worst-case scenario" and "best-case scenario," respectively. Results Forty-three patients underwent procedures for femoroacetabular impingement (FAI) and 9 underwent procedures for soft-tissue pathologies (ST). The median cumulative exposure was 8.6 mGy and 5.0 mGy for FAI patients and ST patients, respectively ( P  = .01). The cumulative effective radiation dose was 490 mrem and 350 mrem for FAI patients and ST patients, respectively ( P  = .47). BMI significantly correlated with cumulative exposure ( P  = .0004) and trended toward significance with cumulative effective dose ( P  = .073). OR staff cumulative occupational exposure was low (9 mrem for the surgeon). Ion chamber data showed that increasing patient BMI resulted in increased occupational exposure. Conclusions The median cumulative effective radiation dose to patients undergoing arthroscopic hip preservation surgery is 490 mrem and results in an excess lifetime risk of death from cancer of 0.025%. Greater BMI correlates with increased cumulative radiation exposure and may increase risk to OR personnel. Occupational exposure to the surgical team from hip arthroscopy ranges from 7 to 9 mrem per 50 hip arthroscopies (+0.0005% excess lifetime risk of death from cancer). Level of Evidence Level IV, diagnostic.

Cumulative Radiation Exposure to Patients Undergoing Arthroscopic Hip Preservation Surgery and Occupational Radiation Exposure to the Surgical Team.

Objective: The purpose of this study is to identify early computed tomography findings around the driveline which would predict mediastinal or left ventricular assist device (LVAD) pocket abscess formation. Materials and Methods: A retrospective analysis was performed on 128 LVAD recipients between January 2007 and December 2011. Infectious complications were subdivided into those affecting the driveline and those resulting in abscess formation either around the LVAD pump or mediastinum. The size and location of infiltrative changes surrounding the driveline were used to predict infection propagation resulting in abscess. Results: Of the 128 patients, 49 (38.3%) patients developed driveline infections and 24 (18.8%) patients developed abscess. 87.5% patients who developed abscess had a preceding driveline infection. The mean time from driveline infection to the development of pump pocket abscess was approximately 7 months. In addition, patients with abscess in the pump pocket or mediastinum had preceding infiltrative changes surrounding the driveline ≥14 mm ( P = 0.0001). A preperitoneal location and size of infiltrative changes ≥14 mm were correlated with a higher likelihood of abscess formation ( P = 0.0002). Conclusion: Our study demonstrates the predictive value of infection/infiltrative changes around the driveline, which increases the risk for abscess formation in the LVAD pump pocket and/or in the mediastinum.

Scott R. Schiffman

Papers

Tumor Targeting with Antibody-Functionalized, Radiolabeled Carbon Nanotubes

Nanobiohybrids as delivery vehicles for camptothecin.

Radiological review of skull lesions

Cumulative Radiation Exposure to Patients Undergoing Arthroscopic Hip Preservation Surgery and Occupational Radiation Exposure to the Surgical Team.

The Role of Computed Tomography in Predicting Left Ventricular Assist Device Infectious Complications.