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A Facile Chemical Strategy to Hydrophobically Modify Solid Nanoparticles using Inverted Micelles Based Multi Capsule for Efficient Intracellular Delivery Enrique A. Daza, Aaron Schwartz-Duval, Kimberly M Volkman, and Dipanjan Pan ACS Biomater. Sci. Eng., Just Accepted Manuscript • DOI: 10.1021/acsbiomaterials.8b00061 • Publication Date (Web): 26 Feb 2018 Downloaded from http://pubs.acs.org on March 5, 2018
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ACS Biomaterials Science & Engineering
A Facile Chemical Strategy to Hydrophobically Modify Solid Nanoparticles using Inverted Micelles Based Multi-Capsule for Efficient Intracellular Delivery Enrique A. Daza,a,b Aaron S. Schwartz-Duval,a,b Kimberly Volkman,a Dipanjan Pan a,b,c,d*
a
Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois,
61801 b
502 N. Busey Av., Biomedical Research Center, Carle Foundation Hospital, Urbana, Illinois,
61801 c
Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-
Champaign, Illinois, USA d
Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign,
Illinois, USA.
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Abstract Theranostic nanoparticles have incredible potential for biomedical applications by enabling visual confirmation of therapeutic efficacy. Numerous issues challenge their clinical translation and are primarily related to the complex chemistry and scalability of synthesizing Nanoparticles. We report a 2-step chemical strategy for high-throughput intracellular delivery of organic and inorganic solid nanoparticles. This process takes an additional step beyond hydrophobic surface modification facilitated by inverted micelle transfer, towards the packing of multiple solid nanoparticles into a soft-shelled lipid capsule, termed the Nano-MultiCapsule (NMC). This technique is high yielding and does not require the complex purification steps in anaerobic/hydrophobic reactions for hydrophobic modification. To demonstrate the efficacy across different material compositions, we separately entrapped ~10 nm gold and carbon nanoparticles (AuNP and CNP) within inverted micelles, and subsequently NMCs, then quantified their internalization in a human breast cancer cell line. For encapsulated AuNPs (NMC-AuNP), we confirmed greater cellular internalization of gold through ICP-OES and TEM analyses. Raman spectroscopic analysis of cells treated with encapsulated CNPs (NMC-CNP) also exhibited high degrees of uptake with apparent intracellular localization as opposed to free CNP treatment. Keywords: Intracellular Delivery, Carbon nanoparticle, Gold Nanoparticle, Inverted Micelle
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ACS Biomaterials Science & Engineering
Introduction Nanoparticles have shown significant potential to redefine conventional medicine. Biomedical applications of nanoparticles are mainly centered around early detection and treatment of a disease. Some cases demonstrate that ‘theranostic’ nanoparticles allow physicians to track the effectiveness of their treatment in patients.1,2 Although there have been comprehensive preclinical studies of these agents, the eventual success of clinical translation has not been fully realized. Numerous issues related to their development, such as scale-up feasibilities, regulatory aspects, and commercialization, challenges their clinical translation. The chemistries involved in theranostic nanoparticle engineering allow for precise tuning of shape, size, and surface chemistry to better enable circumstantial requirements and to serve a specific, or a multitude, of purposes.3–6 One challenge biomedical engineers face when developing a nanoparticle for systemic use is predicting the minimal necessary physiological retention time, which is directly correlated to the nanoparticle’s diameter.7,8 A smaller nanoparticle (10 nm or less) benefits from rapid clearance of the body’s blood stream due to the glomular filtration apparatus in the kidney that possesses a size cut-off at 10 nm.9 Although nanoparticles of 10 nm or less can decrease the chances of accidental particle accumulation and nanoparticle exposure to vital organs,10–15 it minimizes the nanoparticles effective retention time which may be necessary for either imaging or treatment applications as the clearance happens rapidly. On the contrary, nanoparticles between 10 - 300 nm have extended systemic retention times necessary for longer imaging or treatment procedures yet are susceptible to accumulation within the body and may not efficiently reproduce the physical properties that make
