Sunday, September 26, 2021

Nanoparticles—Drug Loading and Release

Drug delivery can affect drug pharmacokinetics, absorption, distribution, metabolism, duration of therapeutic effect, excretion, and toxicity.  Nanoparticles (NPs) are thought to have potential for novel drug delivery and release purposes.

Critical considerations for a successful nano based drug delivery system include its ability:

  • To target specific tissues and cell types 
    • Endocytosis (uptake into the cells)
    • Targeting agent (address tags)
  • To escape from the biological particulate filter 
    • Mononuclear Phagocyte System (clearance of unwanted particulate material)
    • Clearance avoidance 
      • Main NP research question—how is particulate material recognized and cleared?
In this article, we will cover the above four highlighted areas.


Figure 1. Endocytosis (Credit: Mariana Ruiz Villarreal LadyofHats - Own work)


Biological Particulate Filter 


Cells of Mononuclear Phagocytic System (MPS) are cells responsible for the clearance of particulate matter such as bacteria, fungi, viruses, and dying cells from the circulation.

NP association with the host highly evolved MPS is a function of particle opsonization upon contact with blood and rapid recognition of these opsonins via the MPS.[113,115] This is particularly observed in structurally distinct fenestrated vasculature via liver Kupffer cells and splenic macrophages.[127,128]
As soon as nanoparticles enter to the bloodstream, they are prone to aggregation and protein opsonization (protein binding to nanoparticle surface as a tag for immune system recognition). The opsonized nanoparticles could be cleared from the bloodstream by phagocytosis or filtration in the liver, spleen, and kidney. This rapid and non-specific clearance by the immune system results in decreased retention time and thus limits bioavailability. 

To design improved NPs for drug delivery, we need to consider how to  escape from such biological particulate filter and the like, which include:
  • Scavenger endothelial cells
    • Cells responsible for the avid clearance of macromolecules and nanoparticles from the blood circulation
  • Liver sinusoidal endothelial cells (LSECs)
    • Cells largely responsible for removing viruses and small immune complexes from blood
    • Are only pinocytic (vs phagocytotic)
  • Kupffer cells (KCs—localized in liver)
    • Represent the largest population of mononuclear phagocytes in the body.
    • Should virions be aggregated, by whatever means, they may be too large for pinocytic uptake and would then qualify for phagocytic uptake by KC but not LSEC (see Fig. 1).
  • Spleen
    • Spleen is the 2nd largest unit of the mononuclear phagocyte system
    • The spleen is a center of activity of the mononuclear phagocyte system and is analogous to a large lymph node
  • Cells lining the lymph sinuses


Clearance Avoidance Design


Nanoparticle delivery vehicles designed to either avoid or specifically harness this host recognition system (i.e., MPS) could improve payload delivery, reduce inflammatory effects and improve drug efficacy. 
The particle size and surface properties of NPs can be manipulated to avoid rapid clearance by phagocytic cells, allowing both passive and active drug targeting.
Design considerations of clearance avoidance include:
  • Surface modification 
    • By decorating the nanoparticle surface with polyethylene glycol (PEG), carbohydrates, acetyl groups, or protein moieties (arginine-glycine-aspartate (RGD) peptide, albumin), retention time can be altered [6]. 
    • However, such surface modification can also alter the recognition ability for targeted delivery. Thus, the cleanability and biodistribution of therapeutic nanoparticles should be well concerned during the design process.
  • Size consideration
    • Size is one important factor playing role in controlling circulation and biodistribution of therapeutic nanoparticles. 
    • Nanoparticles smaller than 10 nm, can be easily cleared by physiological systems (filtration through the kidney), while particles larger than 200 nm may be cleared by phagocytic cells in the MPS.
    • Accordingly, therapeutic nanoparticles with a size of <100 nm have longer circulation time in the bloodstream.[134]
      • For example, many studies reported that therapeutic nanoparticles in 20–200 nm size showed a higher accumulation rate in tumors because they cannot be recognized by the MPS and filtrated by the kidney.[135-137]

Advantages of Nanoparticle Applications


Drugs with very low solubility possess various biopharmaceutical delivery issues including:
  • Limited bio accessibility after intake through mouth
  • Less diffusion capacity into the outer membrane
  • Require more quantity for intravenous intake 
  • Unwanted after-effects preceding traditional formulated vaccination process. 
However all these limitations could be overcome by the application of nanotechnology approaches in the drug delivery mechanism.  
The shape and size of nanoparticles affects how cell in the body “see” them and thus dictate their distribution, toxicity, and targeting ability.

Most importantly, nanoparticles can cross the BBB providing sustained delivery of medication for diseases that were previously difficult to treat.[133]

Drug designing at the nanoscale has been studied extensively and is by far, the most advanced technology in the area of NP applications because of: 
  • Potential for administration through various routes, including oral, pulmonary, nasal, parenteral, intraocular etc.
  • The possibility to modify their properties like solubility, drug release profiles, diffusivity, bioavailability and immunogenicity by incorporating nanoparticles
    • Adjustments in nanostructures size, shape, hydrophobicity, and surface changes can further enhance the bioactivity of these nanomaterials.
  • Nanostructures stay in the blood circulatory system for a prolonged period and enable the release of amalgamated drugs as per the specified dose. Thus, they cause fewer plasma fluctuations with reduced adverse effects.
  • Being nanosized, these structures penetrate in the tissue system, facilitate easy uptake of the drug by cells, permit an efficient drug delivery, and ensure action at the targeted location. 
    • The uptake of nanostructures by cells is much higher than that of large particles with size ranging between 1 and 10 µm. 
    • Hence, they directly interact to treat the diseased cells with improved efficiency and reduced or negligible side effects.
  • NPs reportedly aid in preventing drugs from being tarnished in the gastrointestinal region and help the delivery of sparingly water-soluble drugs to their target location. 
    • Nanodrugs show higher oral bioavailability because they exhibit typical uptake mechanisms of absorptive endocytosis.
    • For instance, thymoquinone, a bioactive compound in Nigella sativa, is studied after its encapsulation in lipid nanocarrier. After encapsulation, it showed sixfold increase in bioavailability in comparison to free thymoquinone and thus protects the gastrointestinal stuffs.
  • Ability to reach the smallest capillary vessels, due to their tiny volume, and to penetrate the tissues either through the paracellular or the transcellular pathways.
Figure 2. Elements of nanotechnology, which are utilized in therapeutic applications (source: [134])

Research Areas of Nanotechnologies in Drug Delivery


Polymeric nanoparticles can be categorized into nanospheres and nanocapsules both of which are excellent drug delivery systems. Likewise, compact lipid nanostructures and phospholipids including liposomes and micelles (first generation nanoparticle-based lipid systems) are very useful in targeted drug delivery.

The primary goals for research of nanotechnologies in drug delivery include:
  • More specific drug targeting and delivery
  • Reduction in toxicity while maintaining therapeutic effects
  • Greater safety and biocompatibility
  • Faster development of new safe medicines

Drug Loading


Choice of an ideal nano-drug delivery system is decided primarily based on the biophysical and biochemical properties of the targeted drugs being selected for the treatment.

There are two ways through which nanostructures deliver drugs:[126]
  • Passive
    • Drugs are incorporated in the inner cavity of the structure mainly via the hydrophobic effect
    • When the nanostructure materials are targeted to a particular sites, the intended amount of the drug is released because of the low content of the drugs which is encapsulated in a hydrophobic environment.
  • Self-delivery
    • Drugs intended for release are directly conjugated to the carrier nanostructure material for easy delivery.
    • In this approach, the timing of release is crucial as the drug will not reach the target site and it dissociates from the carrier very quickly, and conversely, its bioactivity and efficacy will be decreased if it is released from its nanocarrier system at the right time.
Nanostructures could be utilized as delivery agents by encapsulating drugs or attaching therapeutic drugs and deliver them to target tissues more precisely with a controlled release.[129,130]
The main benefits of these nanoparticles are associated with their surface properties; as various proteins can be affixed to the surface.

Moreover, adjustments in nanostructures size, shape, hydrophobicity, and surface changes can further enhance the bioactivity of these nanomaterials.
>
Figure 3.  Inductive drug release by temperature difference

Figure 4.  Drug release from polymeric gels. (A) Encapsulated drug released concomitant with gel degradation. (B) Release by linker cleavage of covalently tethered drug, followed by gel degradation.



Controlled Drug Release


Controlled and sustained drug release at the target site, improving the therapeutic efficacy and reducing side effects. 

Nanostructures can stay in the blood circulatory system for a prolonged period and enable the release of drugs as per the specified dose. Moreover, pH-, thermo-, ultrasound-, or light-sensitive nanomaterials allow for controlled NP dissociation and triggered drug release. The combination of these approaches can further improve specificity and efficacy of NP-based drug delivery and brings the development of a ‘smart’ or ‘intelligent’ nanosized drug deliver system a major step forward.
How the hydrogel releases the drug is often essential to achieve desirable therapeutic outcomes, and the required duration of drug availability (short term versus long term) and its release profile (continuous versus pulsatile) depend on the specific application.[6] 
With consistent efforts, researchers have strived to engineer nanosized hydrogels by modifying their physical and chemical properties, referring to them as ‘smart’ or ‘intelligent’ hydrogels since they respond to external stimuli like temperature (Fig. 3), pH, light, magnetic and electric fields, ionic strength, or enzymatic environment.

Some NP-based drug deliver system with tunable drug release designs will be discussed in the below subsections.

Ultrasound


Natural biological processes are intricately controlled by the timing and spatial distribution of various cues. To mimic this precise level of control, the physical sizes of gold nanoparticles are utilized to sterically entrap them in hydrogel materials, where they are subsequently released only in response to ultrasound. These nanoparticles can transport bioactive factors to cells and direct cell behavior on-demand.[13]

Drug-Releasing Linkers


Most biodegradable drug-delivery implants encapsulate a drug within gels of limiting pore size that retards diffusion, and release the drug concomitant with hydrolytic degradation—often of ester bonds—of the polymer (Fig. 4A).[131,132]

In contrast, for a Tetra-PEG gels using drug-releasing linkers, they required a porous gel that readily allows diffusion, is substantially stable over the duration of drug release, and degrades subsequent to release of the drug (Fig. 4B).[21]

Smart Targeting of Nanoparticles


One of the more prevalent targeting ligands conjugated to nanoparticles are small molecules. The major advantages of using a small molecule as targeting ligand is its stability, ease of conjugation with nanoparticles, and the potential low cost, assuming it can be chemically synthesized with high yield.
Existence of a multitude of preparation methods of polymeric nanoparticles can control the release characteristics of incorporated therapeutic agents, which allows the delivery of a higher concentration of agents to the target location. 

Moreover, the surface of polymeric nanoparticles could be easily modified and functionalized with a specific recognition ligand which increases the specificity of therapeutic agents in targeted tissue.
In a review article,[140] it  illustrates methods of ligand-nanoparticle functionalization, provides a cross-section of various ligand classes, including small molecules, peptides, antibodies, engineered proteins, or nucleic acid aptamers, and discusses some unconventional approaches currently under investigation.
In this article, we will use oligonucleotides for illustration.

Oligonucleotides—Good ligands for NP Functionalization


Oligonucleotides are short DNA or RNA molecules, oligomers. The various types of oligonucleotides do not only play essential roles within living organisms but also have found widespread applications in different research areas ranging from antisense therapy and siRNA delivery to hierarchical self-assembly for the creation of new materials.[139] Their inherent properties of accurate addressability and programmability, high target specificity, as well as ease of synthesis and functionalization have made oligonucleotides attractive ligands for NP functionalization.[138]
Chemically modified oligonucleotides, such as locked nucleic acids (LNA) or peptide nucleic acids (PNA), have been developed to increase target binding affinity through increased base-stacking and to be enriched with high stability toward nuclease digestion, respectively. 
Taking into account the versatility of oligonucleotides, it is unsurprising, that oligonucleotides as ligands to coat NPs play an important role in the function of nanoparticulate systems. 
Over the last two decades DNA-coated NPs have become increasingly important for applications in nanomedicine. The DNA ligand shell stabilizes the NP core both through sterical and electrostatic interactions resulting in NPs that are highly stable in a variety of complex media. Different conjugation strategies based on direct oligonucleotide chemisorption, physisorption, or involving coupling chemistry have been developed.

References

  1. Nanoparticles—a historical perspective
  2. Preparation and Characterization of Cross-Linked Polymeric Nanoparticles for Enhanced Oil Recovery Applications (pdf)
  3. Polyacrylamide and its deriv ylamide and its derivatives for oil r es for oil recovery (pdf)
  4. Nanosizing of drugs: Effect on dissolution rate
  5. Development and functional characterization of alginate dressing as potential protein delivery system for wound healing
  6. Designing hydrogels for controlled drug delivery (good)
  7. Novavax addresses urgent global public health needs with innovative technology
  8. How the Novavax Vaccine Works
  9. Widder KJ, Senyel AE, Scarpelli GD. Magnetic microspheres: a model system of site specific drug delivery in vivo. Proc Soc Exp Biol Med. 1978;158:141–6.
  10. Nuclear molecular imaging with nanoparticles: radiochemistry, applications and translation
  11. Methods for Synthesis of Nanoparticles and Fabrication of Nanocomposites
  12. NANOPARTICULATE DRUG DELIVERY SYSTEM
  13. Switchable Release of Entrapped Nanoparticles from Alginate Hydrogels.[Adv Healthc Mater. 2015]
  14. Nanosized cationic hydrogels for drug delivery: preparation, properties and interactions with cells. Vinogradov SV, Bronich TK, Kabanov AV. Adv Drug Deliv Rev. 2002 Jan 17; 54(1):135-47.
  15. Applications of Targeted Nano Drugs and Delivery Systems
  16. Langer R. Drug delivery and targeting. Nature. 1998;392:5–10.
  17. Hoare TR, Kohane DS. Hydrogels in drug delivery: Progress and challenges. Polymer. 2008;49:1993–2007.
  18. Liechty WB, Kryscio DR, Slaughter BV, Peppas NA. Polymers for drug delivery systems. Ann Rev Chem Biomol Eng. 2010;1:149–173.
  19. Cohen J. IL-12 deaths: explanation and a puzzle. Science. 1995;270:908–908.
  20. Florence AT, Jani PU. Novel oral drug formulations. Drug Safety. 1994;10:233–266.
  21. Ashley GW, Henise J, Reid R, Santi DV. Hydrogel drug delivery system with predictable and tunable drug release and degradation rates. Proc Natl Acad Sci USA. 2013;110:2318–2323.
  22. Tiwari G, et al. Drug delivery systems: An updated review. Int J Pharm Investig. 2012;2:2–11.
  23. Tibbitt MW, Dahlman JE, Langer R. Emerging frontiers in drug delivery. J Am Chem Soc.
  24. Singh, BN; Prateeksha, Gupta VK; Chen, J; Atanasov, AG (2017). "Organic Nanoparticle-Based Combinatory Approaches for Gene Therapy". Trends Biotechnol. 35 (12): 1121–1124. 2016;138:704–717.
  25. Wang, Zhenming; Wang, Zhefeng; Lu, William Weijia; Zhen, Wanxin; Yang, Dazhi; Peng, Songlin (October 2017). "Novel biomaterial strategies for controlled growth factor delivery for biomedical applications"
  26. Mitragotri S, Lahann J. Physical approaches to biomaterial design. Nat Mater. 2009;8:15–23.
  27. Euliss LE, DuPont JA, Gratton S, DeSimone J. Imparting size, shape, and composition control of materials for nanomedicine. Chem Soc Rev. 2006;35:1095–1104.
  28. Gratton SE, et al. The effect of particle design on cellular internalization pathways. Proc Natl Acad Sci USA. 2008;105:11613–11618.
  29. Geng H, Song H, Qi J, Cui D. Sustained release of VEGF from PLGA nanoparticles embedded thermo-sensitive hydrogel in full-thickness porcine bladder acellular matrix. Nanoscale Res Lett. 2011;6:1–8.
  30. Oh JK, Drumright R, Siegwart DJ, Matyjaszewski K. The development of microgels/nanogels for drug delivery applications. Prog Polym Sci. 2008;33:448–477.
  31. Crommelin DJ, Storm G. Liposomes: from the bench to the bed. J Liposome Res. 2003;13:33–6.
  32. Metselaar JM, Storm G. Liposomes in the treatment of inflammatory disorders. Expert Opin Drug Deliv. 2005;2:465–76.
  33. Noh SY, Nash A, Notman R (2020). "The aggregation of striped nanoparticles in mixed phospholipid bilayers". Nanoscale. 12 (8): 4868–81.
  34. Nanotechnologies: 6. What are potential harmful effects of nanoparticles?
  35. Thake, T.H.F; Webb, J.R; Nash, A.; Rappoport, J.Z.; Notman, R. (2013). "Permeation of polystyrene nanoparticles across model lipid bilayer membranes". Soft Matter. 9 (43): 10265 10274.
  36. Greulich, C.; Diendorf, J.; Simon, T.; Eggeler, G.; Epple, M.; Köller, M. (January 2011). "Uptake and intracellular distribution of silver nanoparticles in human mesenchymal stem cells". Acta Biomaterialia. 7 (1): 347–354.
  37. Compartmentalization Technologies via Self-Assembly and Cross-Linking of Amphiphilic Random Block Copolymers in Water
  38. Drug delivery and nanoparticles: Applications and hazards (good)
  39. The pKa Table Is Your Friend (important)
  40. Nanoparticles as a Targeted Drug Delivery System
  41. Self-Assembled Hydrogel Nanoparticles for Drug Delivery Applications
  42. Gupta M, Gupta AK. In vitro cytotoxicity studies of hydrogel pullulan nanoparticles prepared by AOT/N-hexane micellar system. J Pharm Pharmaceut Sci. 2004;7:38–46.
  43. Biocompatibility and drug delivery systems (good)
  44. S. R. Little and D. S. Kohane, Polymers for intracellular delivery of nucleic acids, J. Mater. Chem., 2008, 18, 832–841
  45. Polymeric Nucleic Acid Delivery for Immunoengineering
  46. Dubernet C., Couvreur P. Nanoparticles in cancer therapy and diagnosis. Adv. Drug Delivery Rev. 2002;54:631–651.
  47. Panyam J., Labhasetwar V. Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv. Drug Delivery Rev. 2003;55:329–347.Moghimi S.M., Hunter A.C., Murray J.C. Long-circulating and target-specific nanoparticles: Theory to practice. Pharmacol. Rev. 2001;53:283–318.
  48. Moghimi S.M., Hunter A.C., Murray J.C. Long-circulating and target-specific nanoparticles: Theory to practice. Pharmacol. Rev. 2001;53:283–318.
  49. Sun T.-M., Du J.-Z., Yan L.-F., Mao H.-Q., Wang J. Self-assembled biodegradable micellar nanoparticles of amphiphilic and cationic block copolymer for siRNA delivery. Biomaterials. 2008;29:4348–4355.
  50. Jain A.K., Goyal A.K., Gupta P.N., Khatri K., Mishra N., Mehta A., Mangal S., Vyas S.P. Synthesis, characterization and evaluation of novel triblock copolymer based nanoparticles for vaccine delivery against hepatitis B. J. Control. Release. 2009;136:161–169.
  51. Niidome T, Yamagata M, Okamoto Y, et al. PEG-modified gold nanorods with a stealth character for in vivo applications. J Control Release. 2006;114:343–7.
  52. M. Goldberg, R. Langer and X. Jia, Nanostructured materials for applications in drug delivery and tissue engineering, J. Biomater. Sci., Polym. Ed., 2007, 18, 241–268.
  53. D. S. Kohane, Microparticles and nanoparticles for drug delivery, Biotechnol. Bioeng., 2007, 96, 203–209
  54. What Are Lipid Nanoparticles in mRNA Vaccines? 
  55. Plard J.P., Bazile D. Comparison of the safety profiles of PLA(50) and Me.PEG-PLA(50) nanoparticles after single dose intravenous administration to rat. Colloids Surf. B. 1999;16:173–183.
  56. Peracchia M.T., Fattal E., Desmaele D., Besnard M., Noel J.P., Gomis J.M., Appel M., d'Angelo J., Couvreur P. Stealth PEGylated polycyanoacrylate nanoparticles for intravenous administration and splenic targeting. J. Control. Release. 1999;60:121–128.
  57. Matsumura Y., Maeda H. A New Concept for macromolecular therapeutics in cancer chemotherapy: Mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs1. Cancer Res. 1986;46:6387–6392.
  58. Brannon-Peppas L., Blanchette J.O. Nanoparticle and targeted systems for cancer therapy. Adv. Drug Delivery Rev. 2004;56:1649–1659.
  59. Moghimi S.M., Hunter A.C., Murray J.C. Nanomedicine: Current status and future prospects. FASEB J. 2005;19:311–330.
  60. Fang C, Shi B, Pei YY, et al. In vivo tumor targeting of tumor necrosis factor-alpha-loaded stealth nanoparticles: Effect of MePEG molecular weight and particle size. Eur J Pharm Sci. 2006;27:27–36.
  61. Shim J, Seok Kang H, Park WS, et al. Transdermal delivery of minoxidil with block copolymer nanoparticles. J Control Release. 2004;97:477–84.
  62. Zhang L, Hu Y, Jiang X, et al. Camptothecin derivative-loaded poly(caprolactone-co-lactide)-b-PEG-b-poly(caprolactone-co-lactide) nanoparticles and their biodistribution in mice. J Control Release. 2004;96:135–48.
  63. A programmable chemical switch based on triggerable Michael acceptors
  64. SELF-IMMOLATIVE CHEMISTRY: Structural Features and Applications in Designing Smart Materials (pdf)
  65. Measuring particle size distribution of nanoparticle enabled medicinal products, the joint view of EUNCL and NCI-NCL. A step by step approach combining orthogonal measurements with increasing complexity
  66. D’Mello SR, Cruz CN, Chen ML, Kapoor M, Lee SL, Tyner KM. The evolving landscape of drug products containing nanomaterials in the United States. Nat. Nanotechnol. 12(6), 523–529 (2017).
  67. US FDA. Guidance Document: Drug Products, Including Biological Products, that Contain Nanomaterials – Guidance for Industry.
  68. EMA. Development of Block-Copolymer-Micelle Medicinal Products (Reference Number EMA/CHMP/130299/2013).
  69. EMA (Committee for Medicinal Products for Human Use). Reflection Paper on the Data Requirements for Intravenous Iron-Based Nano-Colloidal Products Developed with Reference to an Innovator Medicinal Product (2012).
  70. Committee for Human Medicinal Products. Reflection Paper on the Data Requirements for Intravenous Liposomal Products Developed with Reference to Aninnovator Liposomal Product (2013).
  71. US FDA. Liposome Drug Products: Chemistry, Manufacturing, and Controls; Human Pharmacokinetics and Bioavailability; and Labeling Documentation (2018).
  72. Nano-enabled medicinal products: time for an international advanced community?
  73. El-Sayed, M. A. Some interesting properties of metals confined in time and nanometer space of different shapes. Accounts Chem. Res. 34, 257–264 (2001).
  74. Trindade, T., O'Brien, P. & Pickett, N. L. Nanocrystalline semiconductors: synthesis, properties and perspectives. Chem. Mater. 13, 3843–3858 (2001).
  75. Kelly, K. L., Coronado, E., Zhao, L. L. & Schatz, G. C. The optical properties of metal nanoparticles: the influence of size, shape, and dielectric environment. J. Phys. Chem. B. 107, 668–677 (2003).
  76. Seo, W. S. et al. Size-dependent magnetic properties of colloidal Mn3O4 and MnO nanoparticles. Angew. Chem. Int. Ed. 43, 1115–1117 (2004).
  77. Mohanty, A., Garg, N. & Jin, R. A universal approach to the synthesis of noble metal nanodendrites and their catalytic properties. Angew. Chem. Int. Ed. 49, 4962–4966 (2010).
  78. Rao, C. N. R., Kulkarni, G. U., Thomas, P. J. & Edwards, P. P. Size-dependent chemistry: properties of nanocrystals. Chem. Eur. J. 8, 29–35 (2002).
  79. Boal, A. K. et al. Self-assembly of nanoparticles into structured spherical and network aggregates. Nature 404, 746–748 (2000).
  80. Li, P., Kaslan, M., Lee, S. H., Yao, J. & Gao, Z. Progress in exosome isolation techniques. Theranostics 7, 789 (2017).
  81. Lane, R. E., Korbie, D., Anderson, W., Vaidyanathan, R. & Trau, M. Analysis of exosome purification methods using a model liposome system and tunable-resistive pulse sensing. Sci. Rep. 5, 7639 (2015).
  82. Batrakova, E. V. & Kim, M. S. Using exosomes, naturally-equipped nanocarriers, for drug delivery. J. Control. Rel. 219, 396–405 (2015).
  83. Prime, KL; Whitesides, GM (1991). "Self-assembled organic monolayers: model systems for studying adsorption of proteins at surfaces". Science. 252 (5009): 1164–7.
  84. Liu, Wenhao; Greytak, Andrew B.; Lee, Jungmin; Wong, Cliff R.; Park, Jongnam; Marshall, Lisa F.; Jiang, Wen; Curtin, Peter N.; Ting, Alice Y.; Nocera, Daniel G.; Fukumura, Dai; Jain, Rakesh K.; Bawendi, Moungi G. (20 January 2010). 
  85. "Compact Biocompatible Quantum Dots via RAFT-Mediated Synthesis of Imidazole-Based Random Copolymer Ligand". Journal of the American Chemical Society. 132 (2): 472–483.
  86. Gupta AK, Gupta M. Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials. 2005;26:3995–4021.
  87. "Nanoparticles play at being red blood cells". Archived from the original on 1 July 2011. Retrieved 1 July 2011.
  88. Surface-Energy Control and Characterization of Nanoparticle Coatings
  89. Core–shell nanostructures: perspectives towards drug delivery applications
  90. Cancer Cell Membrane-Coated Nanoparticles for Anticancer Vaccination and Drug Delivery
  91. Akerman ME, Chan WC, Laakkonen P, Bhatia SN, Ruoslahti E (2002). "Nanocrystal targeting in vivo". Proceedings of the National Academy of Sciences of the United States of America. 99(20): 12617–12621.
  92. Praaning-van Dalen, DP; Brouwer, A; Knook, DL (December 1981). "Clearance capacity of rat liver Kupffer, Endothelial, and parenchymal cells". Gastroenterology. 81 (6): 1036–44.
  93. Anderson, CL (December 2015). "The liver sinusoidal endothelium reappears after being eclipsed by the Kupffer cell: a 20th century biological delusion corrected". Journal of Leukocyte Biology. 98(6): 875–6.
  94. Ganesan, LP; Mohanty, S; Kim, J; Clark, KR; Robinson, JM; Anderson, CL (September 2011). "Rapid and efficient clearance of blood-borne virus by liver sinusoidal endothelium". PLoS Pathogens. 7 (9): e1002281.
  95. Hoshino, A; Fujioka, K; Oku, T; Nakamura, S; Suga, M; Yamaguchi, Y; Suzuki, K; Yasuhara, M; Yamamoto, K (2004). "Quantum dots targeted to the assigned organelle in living cells". Microbiology and Immunology. 48 (12): 985–94.
  96. Suzuki, KG; Fujiwara, TK; Edidin, M; Kusumi, A (2007). "Dynamic recruitment of phospholipase C at transiently immobilized GPI-anchored receptor clusters induces IP3 Ca2+ signaling: single-molecule tracking study 2". The Journal of Cell Biology. 177 (4): 731–42.
  97. Sung, KM; Mosley, DW; Peelle, BR; Zhang, S; Jacobson, JM (2004). "Synthesis of monofunctionalized gold nanoparticles by fmoc solid-phase reactions". Journal of the American Chemical Society. 126 (16): 5064–5.
  98. Fu, A; Micheel, CM; Cha, J; Chang, H; Yang, H; Alivisatos, AP (2004). "Discrete nanostructures of quantum dots/Au with DNA". Journal of the American Chemical Society. 126 (35): 10832–3.
  99. Howarth, M; Liu, W; Puthenveetil, S; Zheng, Y; Marshall, LF; Schmidt, MM; Wittrup, KD; Bawendi, MG; Ting, AY (2008). "Monovalent, reduced-size quantum dots for imaging receptors on living cells". Nature Methods. 5 (5): 397–9.
  100. van Furth R, Cohn ZA, Hirsch JG, Humphrey JH, Spector WG, Langevoort HL. [Mononuclear phagocytic system: new classification of macrophages, monocytes and of their cell line]. Bull World Health Organ (1972) 47:651–8.
  101. Jokerst, V. J.; Lobovkina, T.; Zare, N. R.; Gambhir, S. S. Nanoparticle PEGylation for imaging and therapy. Nanomedicine 2012, 6, 715– 728.
  102. Hak, S.; Helgesen, E.; Hektoen, H. H.; Huuse, E. M.; Jarzyna, P. A.; Mulder, W. J. M.; Haraldseth, O.; de Lange Davies, C. L. The Effect of Nanoparticle Polyethylene Glycol Surface Density on Ligand-Directed Tumor Targeting Studied in Vivo by Dual Modality Imaging. ACS Nano 2012, 6, 5648– 5658.
  103. Pelaz, B.; del Pino, P.; Maffre, P.; Hartmann, R.; Gallego, M.; Rivera-Fernández, S.; de la Fuente, J. M.; Nienhaus, G. U.; Parak, W. J. Surface Functionalization of Nanoparticles with Polyethylene Glycol: Effects on Protein Adsorption and Cellular Uptake. ACS Nano 2015, 9, 6996– 7008.
  104. He X, Nie H, Wang K, Tan W, Wu X, Zhang P. Anal Chem. 2008;80:9597–9603. 
  105. Huang X, Li L, Liu T, Hao N, Liu H, Chen D, Tang F. ACS Nano. 2011;5:5390–5399. 
  106. Kumar R, Roy I, Ohulchanskky TY, Vathy LA, Bergey EJ, Sajjad M, Prasad PN. ACS Nano. 2010;4:699–708. 
  107. Liu T, Li L, Teng X, Huang X, Liu H, Chen D, Ren J, He J, Tang F. Biomaterials. 2011;32:1657–1668. 
  108. Liu Y, Hu Y, Huang L. Biomaterials. 2014;35:3027–3034. 
  109. Ohno K, Akashi T, Tsujii Y, Yamamoto M, Tabata Y. Biomacromolecules. 2012;13:927–936. 
  110. Owens DE, 3rd, Peppas NA. Int J Pharm. 2006;307:93–102.
  111. Nanoparticle Uptake: The Phagocyte Problem. (good)
  112. Dobrovolskaia MA, Aggarwal P, Hall JB, McNeil SE. Mol Pharm. 2008;5:487–495.
  113. Jenkin CR, Rowley D. J Exp Med. 1961;114:363–374.
  114. Absolom DR. Methods Enzymol. 1986;132:281–318.
  115. Mortimer GM, Butcher NJ, Musumeci AW, Deng ZJ, Martin DJ, Minchin RF. ACS Nano. 2014;8:3357–3366.
  116. Andrade J, Hlady V. Biopolymers/Non-Exclusion HPLC. Springer; 1986. Protein adsorption and materials biocompatibility: a tutorial review and suggested hypotheses; pp. 1–63. 
  117. Andrade JD, Hlady VL, Van Wagenen RA. Pure Appl Chem. 1984;56:1345–1350.
  118. Vertegel AA, Siegel RW, Dordick JS. Langmuir. 2004;20:6800–6807. 
  119. Davidson WS, Jonas A, Clayton DF, George JM. J Biol Chem. 1998;273:9443–9449.
  120. Lord MS, Foss M, Besenbacher F. Nano Today. 2010;5:66–78. 
  121. Walkey CD, Chan WC. Chem Soc Rev. 2012;41:2780–2799. 
  122. Banda NK, Mehta G, Chao Y, Wang G, Inturi S, Fossati-Jimack L, Botto M, Wu L, Moghimi SM, Simberg D. Part Fibre Toxicol. 2014;11:64. 
  123. Nano based drug delivery systems: recent developments and future prospects (good)
  124. Engineering the Dynamics of Cell Adhesion Cues in Supramolecular Hydrogels for Facile Control over Cell Encapsulation and Behavior
  125. Nanoparticles in the clinic: An update post COVID‐19 vaccines
  126. Lu H, Wang J, Wang T, Zhong J, Bao Y, Hao H. Recent progress on nanostructures for drug delivery applications. J Nanomater. 2016;2016:20.
  127. Pouliquen D, Le Jeune J, Perdrisot R, Ermias A, Jallet P. J Magn Reson Im. 1991;9:275–283.
  128. Briley-Saebo K, Bjornerud A, Grant D, Ahlstrom H, Berg T, Kindberg GM. Cell Tissue Res. 2004;316:315–323.
  129. Jahangirian H, Lemraski EG, Webster TJ, Rafiee-Moghaddam R, Abdollahi Y. A review of drug delivery systems based on nanotechnology and green chemistry: green nanomedicine. Int J Nanomed. 2017;12:2957.
  130. Lam P-L, Wong W-Y, Bian Z, Chui C-H, Gambari R. Recent advances in green nanoparticulate systems for drug delivery: efficient delivery and safety concern. Nanomedicine. 2017;12:357–85.
  131. Fredenberg S, Wahlgren M, Reslow M, Axelsson A. The mechanisms of drug release in poly(lactic-co-glycolic acid)-based drug delivery systems—a review. Int J Pharm. 2011;415(1-2):34–52.
  132. Censi R, Di Martino P, Vermonden T, Hennink WE. Hydrogels for protein delivery in tissue engineering. J Control Release. 2012;161(2):680–692.
  133. McMillan J., Batrakova E. Cell delivery of therapeutic nanoparticles. Prog. Mol. Biol. Transl. Sci. 2011;104:563–601.
  134. Therapeutic Nanoparticles and Their Targeted Delivery Applications
  135. Ernsting, M.J.; Murakami, M.; Roy, A.; Li, S.-D. Factors controlling the pharmacokinetics, biodistribution and intratumoral penetration of nanoparticles. J. Control. Release 2013, 172, 782–794.
  136. Wu, W.; Luo, L.; Wang, Y.; Wu, Q.; Dai, H.B.; Li, J.S.; Durkan, C.; Wang, N.; Wang, G.X. Endogenous pH-responsive nanoparticles with programmable size changes for targeted tumor therapy and imaging applications. Theranostics 2018, 8, 3038–3058.
  137. Bhatia, S. Nanoparticles Types, Classification, Characterization, Fabrication Methods and Drug Delivery Applications. In Natural Polymer Drug Delivery Systems: Nanoparticles, Plants, and Algae; Bhatia, S., Ed.; Springer International Publishing: Cham, Switzerland, 2016; pp. 33–93.
  138. Parak, W. J.; Pellegrino, T.; Micheel, C. M.; Gerion, D.; Williams, S. C.; Alivisatos, A. P. Conformation of Oligonucleotides Attached to Gold Nanocrystals Probed by Gel Electrophoresis. Nano Lett. 2003, 3, 33– 36.
  139. Seeman, N. C.; Sleiman, H. F. DNA Nanotechnology. Nat. Rev. Mater. 2017, 3, 17068.
  140. The Smart Targeting of Nanoparticles
  141. Designing spatial and temporal control of vaccine responses (good)
  142. Role of drug delivery technologies in the success of COVID-19 vaccines: a perspective
Posted by at
Labels: , , , , ,

No comments:

Post a Comment

Subscribe to: Post Comments (Atom)