“SMART” Drug Delivery Systems: Double-Targeted pH-Responsive Pharmaceutical Nanocarriers
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To develop targeted pharmaceutical carriers additionally capable of responding to certain local stimuli, such as decreased pH values in tumors or infarcts, targeted long-circulating PEGylated liposomes and PEG-phosphatidylethanolamine (PEG-PE)-based micelles have been prepared with several functions. First, they are capable of targeting a specific cell or organ by attaching the monoclonal antimyosin antibody 2G4 to their surface via pNP-PEG-PE moieties. Second, these liposomes and micelles were additionally modified with biotin or TAT peptide (TATp) moieties attached to the surface of the nanocarrier by using biotin-PE or TATp-PE or TATp-short PEG-PE derivatives. PEG-PE used for liposome surface modification or for micelle preparation was made degradable by inserting the pH-sensitive hydrazone bond between PEG and PE (PEG-Hz-PE). Under normal pH values, biotin and TATp functions on the surface of nanocarriers were "shielded" by long protecting PEG chains (pH-degradable PEG(2000)-PE or PEG(5000)-PE) or by even longer pNP-PEG-PE moieties used to attach antibodies to the nanocarrier (non-pH-degradable PEG(3400)-PE or PEG(5000)-PE). At pH 7.4-8.0, both liposomes and micelles demonstrated high specific binding with 2G4 antibody substrate, myosin, but very limited binding on an avidin column (biotin-containing nanocarriers) or internalization by NIH/3T3 or U-87 cells (TATp-containing nanocarriers). However, upon brief incubation (15-30 min) at lower pH values (pH 5.0-6.0), nanocarriers lost their protective PEG shell because of acidic hydrolysis of PEG-Hz-PE and acquired the ability to become strongly retained on an avidin column (biotin-containing nanocarriers) or effectively internalized by cells via TATp moieties (TATp-containing nanocarriers). We consider this result as the first step in the development of multifunctional stimuli-sensitive pharmaceutical nanocarriers.
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Selective delivery is achieved via novel design of various stimuli-responsive nanomicelles that release drugs based on endogenous or exogenous stimulations such as pH, temperature, ultrasound, light, redox potential, and others.
“Selective delivery is achieved via novel design of various stimuli-responsive nanomicelles that release drugs based on endogenous or exogenous stimulations such as pH, temperature, ultrasound, light, redox potential, and others.”
From Recent Advances in Nanomicelles Delivery Systems. (2020) · cites this paper as [18]
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- Authors
- Sawant, R. M., Hurley, J. P., Salmaso, S., Kale, A., Tolcheva, E., Levchenko, T. S., & Torchilin, V. P.
- Affiliations
- Northeastern University (US)
- Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts 02115
- Corresponding author
- Torchilin, V. P.
- Venue
- Bioconjugate Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2006-06-30
- Volume
- 17
- Issue
- 4
- Pages
- 943-949
- ISSN
- 1043-1802 (ISSN-L)
- 1520-4812
- PMC
- PMC2538444
- OpenAlex
- W2056252055
- Cited by
- 540
- References
- 33
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 8 · 2023: 13 · 2022: 20 · 2021: 20 · 2020: 18 · 2019: 15 · 2018: 27 · 2017: 20 · 2016: 36 · 2015: 38 · 2014: 33 · 2013: 43 · 2012: 51
- FWCI
- 17.81
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Bioconjugate Chemistry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Padua Research Archive (University of Padova) (submittedVersion, other-oa)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01 HL55519, R01HL055519)
- National Cancer Institute (R01CA121838)
- National Institute of Biomedical Imaging and Bioengineering (R01EB001961)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- pH-responsive nanocarriers, PEGylated liposomes, stimuli-responsive drug delivery, targeted drug delivery, TAT peptide, avidin binding, cellular internalization, tumor acidic pH, multifunctional nanocarriers
- MeSH terms
- Drug Carriers, Enzyme-Linked Immunosorbent Assay, Hydrogen-Ion Concentration, Liposomes, Micelles, Magnetic Resonance Spectroscopy, Phosphatidylethanolamines, Polyethylene Glycols, Drug Delivery Systems, Nanoparticles
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