Delivering nanomedicine to solid tumors

Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, 100 Blossom Street, Boston, MA 02114, USA.
Nature Reviews Clinical Oncology (Impact Factor: 14.18). 11/2010; 7(11):653-64. DOI: 10.1038/nrclinonc.2010.139
Source: PubMed


Recent advances in nanotechnology have offered new hope for cancer detection, prevention, and treatment. While the enhanced permeability and retention effect has served as a key rationale for using nanoparticles to treat solid tumors, it does not enable uniform delivery of these particles to all regions of tumors in sufficient quantities. This heterogeneous distribution of therapeutics is a result of physiological barriers presented by the abnormal tumor vasculature and interstitial matrix. These barriers are likely to be responsible for the modest survival benefit offered by many FDA-approved nanotherapeutics and must be overcome for the promise of nanomedicine in patients to be realized. Here, we review these barriers to the delivery of cancer therapeutics and summarize strategies that have been developed to overcome these barriers. Finally, we discuss design considerations for optimizing the delivery of nanoparticles to tumors.

Download full-text


Available from: Triantafyllos Stylianopoulos, Jun 02, 2015
  • Source
    • "Poor lymphatic drainage further leads to low convection due to build-up of high-interstitial fluid pressure (IFP)[28,29]. Nanomedicine transport following systemic injection mainly occurs by extravasation, which includes diffusion and convection and poses multiple barriers in the form of dense interstitial matrix and physicochemical properties of the NCs[30]. Several approaches have come to fore to prime tumors to enhance delivery[31]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: RNA therapeutics could represent the next generation personalized medicine. The variety of RNA molecules that can inhibit the expression of any mRNA using, for example, RNA interference (RNAi) strategies, or increase the expression of a given protein using modified mRNA together with new gene editing strategies open new avenues for manipulating the fate of diseased cells while leaving healthy cells untouched. In addition, these therapeutic RNA molecules can maximize the treatment of diseases and minimize its adverse effects. Yet, the promise of RNA therapeutics is hindered by the lack of efficient delivery strategies to selectively target these molecules into specific cells. Herein, we will focus on the challenges and opportunities of the delivery of therapeutic RNAi molecules into cancer cells with special emphasis on solid tumors. Solid tumors represent more than 80 percent of cancers and some are very challenging to treat, not merely due to physiological barriers but also since the tumor microenvironment (TME) is a complex milieu of accessory cells besides the cancerous cells. In this review, we will highlight various limiting factors to successful delivery, current clinical achievements and future outlook focusing on RNAi therapeutics to the TME.
    Full-text · Article · Jun 2016 · Current Opinion in Biotechnology
  • Source
    • "Additionally, they should be expressed homogenously on all targeted tumor cells and the selected targeting agent should be abundant, have high affinity and specificity of binding to cell surface receptor.[128,142]To achieve active targeting, nanoparticles should be equipped with functional molecules (targeting agents) which specifically recognize and bind to molecular markers present on tumor vasculature or cancer cells.[135,144]Examples of targeting agents include antibodies and their fragments, lectins, other proteins, lipoproteins , hormones, peptides, nucleic acids, mono-, oligo-and polysaccharides , and some low molecular weight ligands, such as folic acid (FA).[141,145]The attaching of the targeting agents to the surface of the nanoparticles can be performed by a variety of conjugation chemistries.[131]These "
    [Show abstract] [Hide abstract]
    ABSTRACT: Nanomedicine, the application of nanotechnology to medicine, is being increasingly used to improve and exploit the advantages of efficient drug delivery. Different nanodevices have been developed in recent years, among them protein-based nanoparticles which have gained considerable interest. Albumin is a versatile protein carrier with several characteristics that make it an ideal candidate for drug delivery, such as its availability, its biocompatibility, its biodegradability, and its lack of toxicity and immunogenicity. This review embodies an overview of different methods available for production of albumin-based nanoparticles, with focus on high-energy emulsification methods. A comparison between production by using sonication, which involves acoustic cavitation, and the high pressure homogenization method, where occurs hydrodynamic cavitation, is presented. Taking into account important properties of nanoparticles required for intravenous administration, the use of poloxamers, tri-block copolymer surfactants is discussed as it improves blood circulation time and bioavailability of nanoparticles. Thus, nanoparticles can be engineered to provide adequate features to therapeutic applications, in which can be included surface functionalization with targeting agents. Different albumin-based formulations and their therapeutic applications are presented in this review, with emphasis on applications in cancer therapy, where albumin-based strategies are promising for targeted drug delivery in innovative clinical strategies.
    Full-text · Article · Jan 2016 · Current pharmaceutical design
  • Source
    • "Nanoparticle size also affects the intracellular trafficking, which can affect tumor accumulation [28] [29]. However, the EPR effect varies depending on the tumor model and patient, and there can be a huge variation between different areas of a single tumor [30] [31]. To overcome the above drawbacks related to passive targeting, " active targeting " was developed. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Bioavailability of baicalin (BAI), an example of traditional Chinese medicine, has been modified by loading into liposome. Several liposome systems of different composition i.e., lipid/cholesterol (L), long-circulating stealth liposome (L-PEG) and folate receptor (FR)—targeted liposome (L-FA) have been used as the drug carrier for BAI. The obtained liposomes were around 80 nm in diameter with proper zeta potentials about −25 mV and sufficient physical stability in 3 months. The entrapment efficiency and loading efficiency of BAI in the liposomes were 41.0–46.4% and 8.8–10.0%, respectively. The morphology details of BAI lipsosome systems i.e., formation of small unilamellar vesicles, have been determined by cryogenic transmission electron microscopy (cryo-TEM) and small angle X-ray scattering (SAXS). In vitro cytotoxicity of BAI liposomes against HeLa cells was evaluated by MTT assay. BAI loaded FR-targeted liposomes showed higher cytotoxicity and cellular uptake compared with non-targeted liposomes. The results suggested that L-FA-BAI could enhance anti-tumor efficiency and should be an effective FR-targeted carrier system for BAI delivery.
    Full-text · Article · Nov 2015 · Colloids and surfaces B: Biointerfaces
Show more