Abstract IA18: Targeted polymeric nanoparticles: From academic innovations to clinical trials and lessons learned
Authors: Omid C. Farokhzad
Journal: Cancer Research (2017)

Abstract A variety of organic and inorganic materials have been utilized to generate nanoparticles for drug delivery applications, including polymeric nanoparticles, dendrimers, nanoshells, liposomes, nucleic acid based nanoparticles, magnetic nanoparticles, and virus nanoparticles. The two most commonly used systems are polymeric nanoparticles and liposomes [1, 2]. Controlled release polymer technology has impacted virtually every branch of medicine, including ophthalmology, pulmonary, pain medicine, endocrinology, cardiology, orthopedics, immunology, neurology and dentistry, with several of these systems in clinical practice today such as Atridox, Lupron Depot, Gliadel, Zoladex, Trelstart Depot, Risperidol Consta and Sandostatin LAR. The annual worldwide market of controlled release polymer systems which extends beyond drug delivery is now estimated at $100 billion and these systems are used by over 100 million people each year. Polymeric nanoparticles can deliver drugs in the optimum dosage over time, thus increasing the efficacy of the drug, maximizing patient compliance and enhancing the ability to use highly toxic, poorly soluble, or relatively unstable drugs. These systems can also be used to co-deliver two or more drugs for combination therapy [3]. The surface engineering of these nanoparticles may yield them “stealth” to prolong their residence in blood [4] and the functionalization of these particles with targeting ligands can differentially target their delivery or uptake by a subset of cells [5], further increasing their specificity and efficacy [6]. The successful clinical translation of therapeutic nanoparticles requires optimization of many distinct parameters including: variation in the composition of the carrier system, drug loading efficiency, surface hydrophilicity, surface charge, particle size, density of possible ligands for targeting, etc., resulting in a large number of potential variables for optimization which is impractical to achieve using a low throughput approach. More recently combinatorial approaches have been developed to precisely engineer nanoparticles and screen multiple nanoparticle characteristics simultaneously with the goal of identifying formulations with the desired physical and biochemical properties for each specific application [7]. The goal of this talk is to review our efforts in the design and optimization of polymeric nanoparticles for medical applications, which formed the foundation for the clinical translation of the first-in-human targeted and controlled-release nanoparticles, BIND-014 and SEL-068 [8, 9]. References 1. Kamaly et al. Targeted polymeric therapeutic nanoparticles: design, development and clinical translation. Chem Soc Rev. 2012 41:2971-3010. 2. Brannon-Peppas, L. and J.O. Blanchette, Nanoparticle and targeted systems for cancer therapy. Adv Drug Deliv Rev, 2004. 56(11): p. 1649-59. 3. Zhang, L., et al., Co-delivery of hydrophobic and hydrophilic drugs from nanoparticle-aptamer bioconjugates. ChemMedChem, 2007. 2(9): p. 1268-71. 4. Gref, R., et al., Biodegradable long-circulating polymeric nanospheres. Science, 1994. 263(5153): p. 1600-3. 5. Farokhzad, O.C., et al., Nanoparticle-aptamer bioconjugates: a new approach for targeting prostate cancer cells. Cancer Res, 2004. 64(21): p. 7668-72. 6. Farokhzad, O.C., et al., Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo. Proc Natl Acad Sci U S A, 2006. 103(16): p. 6315-20. 7. Gu, F., et al., Precise engineering of targeted nanoparticles by using self-assembled biointegrated block copolymers. Proc Natl Acad Sci U S A, 2008. 105(7): p. 2586-91. 8. Shi, J., et al., Self-Assembled Targeted Nanoparticles: Evolution of Technologies and Bench to Bedside Translation., 2011. 50(31):p. 7027-31. Epub 2011 Jun 22. 9 . Hrkach J, Von Hoff D, Ali MM, Andrianova E, Auer J, Campbell T, De Witt D, Figa M, Figueiredo M, Horhota A, Low S, McDonnell K, Peeke E, Retnarajan B, Sabnis A, Schnipper E, Song JJ, Song YH, Summa J, Tompsett D, Troiano G, Van Geen Hoven T, Wright J, Lorusso P, Kantoff PW, Bander NH, Sweeney C, Farokhzad OC, Langer R, Zale S. Preclinical Development and Clinical Translation of a PSMA-Targeted Docetaxel Nanoparticle with a Differentiated Pharmacological Profile. Sci Transl Med. 2012 Apr 4;4(128):128ra39. PMID:22491949 Citation Format: Omid C. Farokhzad. Targeted polymeric nanoparticles: From academic innovations to clinical trials and lessons learned. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr IA18.