Understanding nano-bio interactions to improve nanocarriers for drug delivery
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troduction Nanotechnology has demonstrated great potential to improve cancer treatments by affecting the ways in which cancer is diagnosed, prevented, and treated in the clinic.1–4 In particular, targeted drug delivery using nanoscale carriers holds great promise to substantially improve therapeutic indices (the ratio between the toxic dose and the therapeutic dose of a drug) of incorporated drug molecules; in fact, a number of them are currently under advanced-stage clinical trials or are being used in clinical settings.5,6 Although formidable progress has been achieved in this field, problems related to variable pharmacokinetics, nanoparticle (NP) instability, insufficiently selective tumor accumulation, and premature drug release continue to plague their fast clinical translation.5,7,8 One of the major drawbacks of most, if not all, NP systems can be linked to their inability to maintain their designed biological functions in various physiological and pathological conditions.9,10 Therefore, to design an effective NP system, it is necessary to develop a comprehensive understanding of the interactions that occur between the nanomaterials and biological systems (i.e., nano-bio interactions) at each stage of the drug delivery process.
Figure 1 depicts the important in vivo barriers that NPs encounter during their journey from injection to reaching targets in the human body. To achieve a successful therapeutic result, NPs must survive blood circulation, accumulate at the tumor site, diffuse through the extracellular matrix (ECM), interact with the cell membrane, internalize into the target cell, and reach the subcellular target. At each stage, the surrounding microenvironment plays a significant, yet differing role in determining the fate of the NP.11–13 The considerable differences between the important interactions at each step necessitate the development of NPs that are optimally engineered to function in various physiological settings. This article summarizes recent advances in the understanding of nano-bio interactions occurring at those multiple stages by dividing it into sections that describe interactions of NPs with the tumor microenvironment, membranes and receptors, and intracellular compartments. Within each section, we discuss the chemical and structural compositions of each biological environment, challenges associated with NP delivery to that environment, and various approaches implemented to overcome the challenges to enable the formation of desired nanobio interactions. It is our aim to provide a succinct overview
Ryan M. Pearson, University of Illinois at Chicago; [email protected] Hao-jui Hsu, University of Illinois at Chicago; [email protected] Jason Bugno, University of Illinois at Chicago; [email protected] Seungpyo Hong, University of Illinois at Chicago; [email protected] DOI: 10.1557/mrs.2014.9
© 2014 Materials Research Society
MRS BULLETIN • VOLUME 39 • MARCH 2014 • www.mrs.org/bulletin
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UNDERSTANDING NANO-BIO INTERACTIONS TO IMPROVE NANOCARRIERS FOR DRUG DELIVERY
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