Manganese-loaded lipid-micellar theranostics for simultaneous drug and gene delivery to lungs
Open accessAbstract
Gadolinium (Gd) contrast agents are predominantly used for T(1) MR imaging. However, the high toxicity of Gd(3+) and potential side effects including nephrogenic systemic fibrosis have led to the search for alternative T(1) contrast agents. Since manganese (Mn) has paramagnetic properties with five unpaired electrons that permit high spin number, long electronic relaxation times, and labile water exchange, we evaluated Mn as a T(1) magnetic resonance imaging (MRI) contrast agent for lung imaging. Here we report on the design and synthesis of multifunctional lipid-micellar nanoparticles (LMNs) containing Mn oxide (M-LMNs) for MRI that can also be used for DNA and drug delivery. Oleic acid-coated MnO nanoparticles were encapsulated in micelles composed of polyethylene glycol (PEG-2000), phosphatidylethanolamine (PE), DC-cholesterol, and dioleoyl-phosphatidylethanolamine (DOPE). The particles are taken up in vitro by human embryonic kidney (HEK293), Lewis lung carcinoma (LLC1), and A549 cells and are devoid of cytotoxicity. When administered to mice intranasally, they preferentially accumulate in the lungs. In vitro phantom and ex vivo lung MRI results confirmed that M-LMNs are able to enhance T(1) MRI contrast. M-LMNs loaded with plasmid DNA and/or doxorubicin are efficiently taken up by HEK293 cells in vitro and by target cells in vivo. Taken together, these results demonstrate that M-LMNs are capable of simultaneously providing MRI contrast and DNA and/or drug delivery to target cells in the lung and therefore may prove useful as a lung theranostic, especially for lung cancers.
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Polymeric nanomicelles (PNMs) are prepared from amphiphilic polymers, range in size from 1 to 200 nm, and contain an inner hydrophobic core and an outer hydrophilic shell; the outer shell controls pharmacokinetic properties and the inner core is responsible for drug entrapment, stability, and drug-release characteristics.
“Another category is polymeric nanomicelles (PNMs) prepared from amphiphilic polymers; they have a size that ranges from 1 to 200 nm. This type of nanoparticles contains two functional portions, an “inner core” and an “outer shell”.”
From Recent Advances in Nanomicelles Delivery Systems. (2020) · cites this paper as [43]
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Hussain, Z. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-815720-6.00011-3 · Cited by 2 · see citing works
Xu, Y., Melkis, K., Sia, C. T., & Sarker, D. K. (2018) · Current Nanomedicine · doi:10.2174/2405461503666180628155014 · Cited by 1 · see citing works
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Shaikh, S. (2022) · Springer eBooks · doi:10.1007/978-981-16-9535-3_21 · Cited by 1 · see citing works
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Ashique, S., Garg, A., Hussain, A., Bhatt, S., Agrawal, A., & Mishra, N. (2023) · Springer eBooks · doi:10.1007/978-981-99-0361-0_12 · Cited by 1 · see citing works
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Costanzo, M., Carton, F., & Malatesta, M. (2017) · Istituto Lombardo - Accademia di Scienze e Lettere - Incontri di Studio · doi:10.4081/incontri.2017.269
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Nanomicelles for the management of COPD
Siddiqui, A., Fairy, Jain, P., Mirza, A., & Iqbal, Z. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-43946-9.00012-4
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Xie, Y.-K., Wang, H., Xiang, L., Shen, Y.-C., Yang, Y., Liu, J., & Teng, X. (2026) · Molecules · doi:10.3390/molecules31132238
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- Authors
- Howell, M., Mallela, J., Wang, C., Ravi, S., Dixit, S., Garapati, U., & Mohapatra, S.
- Affiliations
- University of South Florida (US)
- Corresponding author
- Mohapatra, S.
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2013-04
- Volume
- 167
- Issue
- 2
- Pages
- 210-218
- ISSN
- 0168-3659 (ISSN-L)
- PMC
- PMC3783961
- OpenAlex
- W2012144021
- Cited by
- 65
- References
- 38
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 3 · 2023: 6 · 2022: 9 · 2021: 1 · 2020: 3 · 2019: 7 · 2018: 5 · 2017: 6 · 2016: 3 · 2015: 5 · 2014: 7 · 2013: 3
- FWCI
- 2.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1r41ca139785-01a1)
- U.S. Forest Service
- National Cancer Institute (1R41CA139785, R01CA152005, R41 CA139785)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Materials Chemistry › Lanthanide and Transition Metal Complexes
- Keywords
- manganese oxide nanoparticles, T1 contrast agents, lung cancer, gene delivery, doxorubicin delivery, plasmid DNA delivery, intranasal administration, nanoparticle uptake, gadolinium alternatives, nephrogenic systemic fibrosis
- MeSH terms
- Animals, DNA, Doxorubicin, Humans, Mice, Inbred C57BL, Micelles, Oxides, Tissue Distribution, Drug Delivery Systems, Manganese Compounds, Gene Transfer Techniques, Oleic Acid, Cell Line, Tumor, Mice, Metal Nanoparticles, HEK293 Cells
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