Engineered Polymeric Materials for Biological Applications: Overcoming Challenges of the Bio–Nano Interface
Abstract
:1. Introduction
2. Interactions in the Blood Stream
2.1. Opsonization
2.1.1. The Protein Corona
2.1.2. Measuring and Monitoring Opsonization
2.2. Hemolysis
3. Biological Fate of Nanomedicines
3.1. Biodistribution
3.2. Clearance Pathways
4. Gathering at the Tumor Site
4.1. Extravasation
4.1.1. Impact of Vessel Architecture
4.1.2. Role of Endothelial Integrity
4.1.3. Emerging Tools for Imaging and Overcoming the Endothelial Barrier
4.2. Tumor Tissue Distribution
4.2.1. Tumor Stroma and Microenvironments
4.2.2. Spatial Regulation of Receptor Expression
4.2.3. Downstream Influence of Opsonization on Receptor Affinity
4.2.4. Current and Emerging Tools for Improving Penetration of the Tumor Mass
5. Cellular Level Interactions and Behaviors
5.1. Internalization
5.1.1. Nanoparticle Properties That Influence Cell Internalization
5.1.2. Tools to Understand Cellular Internalization and Limitations of In Vitro Models
5.2. Endosomal Escape
5.2.1. Engineering Materials to Escape the Endosome
5.2.2. Tools to Understand Endosomal Escape
5.3. Trafficking to Subcellular Locations
5.3.1. Trafficking to the Nucleus
5.3.2. Trafficking to the Mitochondria
5.3.3. Emerging Tools for Quantification of Sub-Cellular Localization
6. Conclusions
Supplementary Files
Supplementary File 1Funding
Acknowledgments
Conflicts of Interest
References
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Biological Barrier | Tools to Overcome | Current Challenges | Referred Section |
---|---|---|---|
Interactions in the Blood Stream | Tuning Nanoparticle Physicochemical Properties Pre-Incubation/First pass Artificial Hard Corona | Protein corona has not been extensively profiled for soft nanoparticles The plasma protein content between patients varies | Section 2.1.1 |
Section 2.1.2 | |||
Biodistribution | Nanoparticle Biophysical Properties Incorporation of Targeting Ligands Pre-Targeting Method Hitchhike onto Red Blood Cell | Defined sized cutoff for soft nanoparticle clearance remains challenging | Section 3.1 and Section 3.2 |
Stealth property will be voided | Section 3.2 | ||
Section 2.2 | |||
Gathering at Tumor Site | Nanoparticle Size Nanoparticle Hardness Vascular Normalization and Remodeling | Section 4.1.2 | |
Potential to induce metastasis | Section 4.1.3 | ||
Tumor Tissue Distribution | Nanoparticle Physicochemical Properties Charge-Switching Nanoparticles Size-Switching Nanoparticles Sheddable PEG Corona Macrophage Shuttling | Few studies report on the intratumoral distribution | Section 4.2.4 |
Prevents use of environmentally-responsive polymers | |||
Receptor Affinity | Influenced by degree of opsonization | Section 4.2.3 | |
Internalization | Nanoparticle Physicochemical Properties | Factors influencing nanoparticle internalization are not extensively investigated | Section 5.1.1 |
Polymer Composition (e.g., Fluorous Substitution) Detachable Particle Corona Charge-Switching Particle Nanoparticle–Cell Membrane Fusion | |||
Endosomal Escape | pH-Responsive Materials that Membrane Interact or Swell Modifying the Therapeutic with Cell-Penetrating Peptides Modifying the Therapeutic Physicochemical Properties Incorporation of a Photosensitizer | Internalization must be faster than material activation at tumor microenvironment pH | Section 5.2.1 |
Requires encapsulation for selective delivery | |||
Limitations with depth of penetration of light and toxicity | |||
Subcellular Trafficking | (Nucleus) <9 nm Diameter of Nanoparticle or Therapeutic Conjugation of a Nuclear Localization Signal (Mitochondria) Incorporation of Mitochondrotropic Polymers Conjugation of a Mitochondria Targeting Signal | Factors influencing nanoparticle subcellular trafficking are not extensively investigated | Section 5.3.1 |
Section 5.3.2 |
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Simpson, J.D.; Smith, S.A.; Thurecht, K.J.; Such, G. Engineered Polymeric Materials for Biological Applications: Overcoming Challenges of the Bio–Nano Interface. Polymers 2019, 11, 1441. https://doi.org/10.3390/polym11091441
Simpson JD, Smith SA, Thurecht KJ, Such G. Engineered Polymeric Materials for Biological Applications: Overcoming Challenges of the Bio–Nano Interface. Polymers. 2019; 11(9):1441. https://doi.org/10.3390/polym11091441
Chicago/Turabian StyleSimpson, Joshua D, Samuel A Smith, Kristofer J. Thurecht, and Georgina Such. 2019. "Engineered Polymeric Materials for Biological Applications: Overcoming Challenges of the Bio–Nano Interface" Polymers 11, no. 9: 1441. https://doi.org/10.3390/polym11091441
APA StyleSimpson, J. D., Smith, S. A., Thurecht, K. J., & Such, G. (2019). Engineered Polymeric Materials for Biological Applications: Overcoming Challenges of the Bio–Nano Interface. Polymers, 11(9), 1441. https://doi.org/10.3390/polym11091441