Ultrasound-enhanced tumor targeting of polymeric micellar drug carriers
Open accessAbstract
Cancer chemotherapy is often complicated by toxic side effects of anticancer drugs. We are developing a new modality of tumor chemotherapy aimed at circumventing side effects of treatment via drug targeting to tumors. The technique is based on drug encapsulation in polymeric micelles followed by a controlled drug release at a target site triggered by ultrasonic irradiation. The encouraging in vitro results of previous years warranted animal experiments for verification of the in vivo feasibility of the proposed technique. We report here on the effect of ultrasound on a biodistribution of a micellar drug carrier (fluorescently labeled Pluronic micelles) in ovarian cancer-bearing nu/nu mice. The degree of carrier accumulation in the cells of various organs was characterized by flow cytometry. Polymeric micelles were formed in either pure Pluronic P-105 solutions (unstabilized micelles) or 1:1 (weight) mixtures of Pluronic P-105 with PEG-diacylphospholipid (stabilized micelles). Intraperitoneal (ip) and intravenous (iv) injections were compared. The data showed that a 30 s ultrasonic irradiation by 1 or 3 MHz ultrasound applied locally to the tumor significantly enhanced accumulation of Pluronic in the tumor cells, which was observed for both ip and iv injections and for unstabilized and stabilized micelles. The data indicated targeting of Pluronic micelles to the tumors; the degree of targeting was enhanced by a local tumor sonication.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The results showed that locally applied irradiation of the tumor with 1-3 MHz ultrasound during 30 s resulted in considerable accumulation of both types of Pluronic nanomicelles after intraperitoneal and intravenous injections.
“The results showed that locally applied to the irradiation of the tumor with 1–3 MHz ultrasound during 30 s resulted in considerable accumulation of both types of Pluronic nanomicelles after intraperitoneal and intravenous injections.”
From Recent Advances in Nanomicelles Delivery Systems. (2020) · cites this paper as [208]
The selectivity of ultrasound-responsive Pluronic-based nanomicelles toward tumors cells was demonstrated.
“Thus, the selectivity of ultrasound-responsive Pluronic-based nanomicelles toward tumors cells was demonstrated.”
From Recent Advances in Nanomicelles Delivery Systems. (2020) · cites this paper as [208]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Conjugates of anticancer agents and polymers: advantages of macromolecular therapeutics in vivo
Maeda, H., Seymour, L. W., & Miyamoto, Y. (1992) · Bioconjugate Chemistry · doi:10.1021/bc00017a001 · Cited by 563 · see citing works
Collins, P. D., Rosano, G. M. C., Sarrel, P. M., Ulrich, L. G., Adamopoulos, S. N., Beale, C. M., McNeill, J. G., & Poole-Wilson, P. A. (1995) · Circulation · doi:10.1161/01.cir.92.1.24 · Cited by 530 · see citing works
Kabanov, A. V., Batrakova, E. V., & Miller, D. W. (2003) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(02)00176-x · Cited by 325 · see citing works
Alakhov, V. Y., Moskaleva, E. Y., Batrakova, E. V., & Kabanov, A. V. (1996) · Bioconjugate Chemistry · doi:10.1021/bc950093n · Cited by 304 · see citing works
Batrakova, E. V., Li, S., Vinogradov, S. V., Alakhov, V. Y., Miller, D. W., & Kabanov, A. V. (2001) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)29254-5 · Cited by 292 · see citing works
Batrakova, E. V., Lee, S., Li, S., Venne, A., Alakhov, V. Y., & Kabanov, A. V. (1999) · Pharmaceutical Research · doi:10.1023/a:1018942823676 · Cited by 289 · see citing works
Factors affecting acoustically triggered release of drugs from polymeric micelles
Husseini, G. A., Myrup, G. D., Pitt, W. G., Christensen, D. A., & Rapoport, N. Y. (2000) · Journal of Controlled Release · doi:10.1016/s0168-3659(00)00278-9 · Cited by 228 · see citing works
Self-citationVenne, A., Li, S., Mandeville, R., Kabanov, A. V., & Alakhov, V. Y. (1996) · PubMed · Cited by 225 · see citing works
Marin, A., Sun, H., Husseini, G. A., Pitt, W. G., Christensen, D. A., & Rapoport, N. Y. (2002) · Journal of Controlled Release · doi:10.1016/s0168-3659(02)00262-6 · Cited by 213 · see citing works
Batrakova, E. V., Li, S., Miller, D. W., & Kabanov, A. V. (1999) · Pharmaceutical Research · doi:10.1023/a:1018990706838 · Cited by 206 · see citing works
Drug delivery in polymeric micelles: from in vitro to in vivo
Rapoport, N. Y. (2003) · Journal of Controlled Release · doi:10.1016/s0168-3659(03)00218-9 · Cited by 191 · see citing works
Self-citationStabilization and activation of Pluronic micelles for tumor-targeted drug delivery
Rapoport, N. Y. (1999) · Colloids and Surfaces B Biointerfaces · doi:10.1016/s0927-7765(99)00063-6 · Cited by 181 · see citing works
Self-citationCombined cancer therapy by micellar-encapsulated drug and ultrasound
Rapoport, N. Y. (2004) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2003.09.048 · Cited by 158 · see citing works
Self-citationUltrasound-triggered drug targeting of tumors in vitro and in vivo
Rapoport, N. Y., Christensen, D. A., Fain, H. D., Barrows, L. R., & Gao, Z. (2004) · Ultrasonics · doi:10.1016/j.ultras.2004.01.087 · Cited by 150 · see citing works
Self-citationRapoport, N. Y., Marin, A., Luo, Y., Prestwich, G. D., & Muniruzzaman, M. (2002) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.10006 · Cited by 128 · see citing works
Self-citationRapoport, N. Y., Herron, J. N., Pitt, W. G., & Pitina, L. (1999) · Journal of Controlled Release · doi:10.1016/s0168-3659(98)00149-7 · Cited by 123 · see citing works
Self-citationAcoustic activation of drug delivery from polymeric micelles: effect of pulsed ultrasound
Marin, A., Muniruzzaman, M., & Rapoport, N. Y. (2001) · Journal of Controlled Release · doi:10.1016/s0168-3659(01)00216-4 · Cited by 112 · see citing works
Self-citationCalcium Antagonists in Coronary Artery Disease and Hypertension
Yusuf, S. (1995) · Circulation · doi:10.1161/01.cir.92.5.1079 · Cited by 110 · see citing works
Shiah, J.-G., Sun, Y., Kopečková, P., Peterson, C. M., Straight, R. C., & Kopec̆ek, J. (2001) · Journal of Controlled Release · doi:10.1016/s0168-3659(01)00325-x · Cited by 105 · see citing works
Mechanism of the ultrasonic activation of micellar drug delivery
Marin, A., Muniruzzaman, M., & Rapoport, N. (2001) · Journal of Controlled Release · doi:10.1016/s0168-3659(01)00363-7 · Cited by 102 · see citing works
Self-citationKinetics of ultrasonic release of doxorubicin from pluronic P105 micelles
Husseini, G. A., Rapoport, N. Y., Christensen, D. A., Pruitt, J. D., & Pitt, W. G. (2002) · Colloids and Surfaces B Biointerfaces · doi:10.1016/s0927-7765(01)00273-9 · Cited by 100 · see citing works
Self-citationRapid Quantitation from Inhomogeneously Broadened EPR Spectra by a Fast Convolution Algorithm
Smirnov, A. I., & Belford, R. L. (1995) · Journal of Magnetic Resonance Series A · doi:10.1006/jmra.1995.1057 · Cited by 95 · see citing works
In vivo target-specific delivery of macromolecular agents with MR-guided focused ultrasound.
Bednarski, M. D., Lee, J. W., Callstrom, M. R., & Li, K. C. (1997) · Radiology · doi:10.1148/radiology.204.1.9205257 · Cited by 89 · see citing works
Schaer, G. L., Spaccavento, L. J., Browne, K. F., Krueger, K. A., Krichbaum, D. W., Phelan, J. M., Fletcher, W. O., Grines, C. L., Edwards, S., Jolly, M. K., et al. (1996) · Circulation · doi:10.1161/01.cir.94.3.298 · Cited by 86 · see citing works
pH-sensitive hemolysis by random copolymers of alkyl acrylates and acrylic acid
Murthy, N., Chang, I., Stayton, P. S., & Hoffman, A. S. (2001) · Macromolecular Symposia · doi:10.1002/1521-3900(200107)172:1 · Cited by 53 · see citing works
Intracellular uptake of Pluronic copolymer: effects of the aggregation state
Muniruzzaman, M., Marin, A., Luo, Y., Prestwich, G. D., Pitt, W. G., Husseini, G. A., & Rapoport, N. Y. (2002) · Colloids and Surfaces B Biointerfaces · doi:10.1016/s0927-7765(01)00329-0 · Cited by 46 · see citing works
Self-citationSvenson, S. (2004) · ACS symposium series · doi:10.1021/bk-2004-0879.ch001 · Cited by 43 · see citing works
Frazzini, V. I., Kagetsu, N. J., Johnson, C. E., et al. (1997) · Radiology · doi:10.1148/radiology.204.1.9205258 · Cited by 37 · see citing works
Tóth, K., Bogár, L., Juricskay, I., et al. (1997) · PubMed · Cited by 30 · see citing works
Potential anticancer agents--nitroxyl derivatives of Rubomycin.
Nm, E., Np, K., & Rf, D. (1985) · PubMed · Cited by 16 · see citing works
Advances in Controlled Drug Delivery
Dinh, S. M., & Liu, P. (2003) · ACS symposium series · doi:10.1021/bk-2003-0846 · Cited by 14 · see citing works
Rapoport, N. Y., Marin, A., Muniruzzaman, M., & Christensen, D. A. (2003) · ACS symposium series · doi:10.1021/bk-2003-0846.ch007 · Cited by 13 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 4
- [7]Rapoport N, Marin A, Christensen D. Ultrasound-Activated Micellar Drug Delivery. Drug Delivery Syst Sci. 2002;2:37–46. [Google Scholar]
- [19]Hermanson, G. T. Bioconjugate techniques; Academic Press: San Diego, 1996; pp 303–306.
- [26]Batrakova E, Alakhov V, Kabanov A. Selective energy depletion and sensitization of multiple drug resistant cancer cells by Pluronic block copolymer. Polym Prepr (Am Chem Soc, Div Polym Chem) 2000;41:1739–1740. [Google Scholar]
- [30]Yusuf S. Evaluation of RheothRx, a novel hemorheologic agent, in acute myocardial infarction. Circulation. 1995;92(Suppl I):I–24 . (Abstract). [Google Scholar]
Cited by
Sorted by citations
Targeting multidrug resistance in cancer
Szakács, G., Paterson, J. K., Ludwig, J. A., Booth-Genthe, C., & Gottesman, M. M. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd1984 · Cited by 3,609 · see citing works
Kamaly, N., Yameen, B., Wu, J., & Farokhzad, O. C. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00346 · Cited by 3,070 · see citing works
Batrakova, E. V., & Kabanov, A. V. (2008) · Journal of Controlled Release · doi:10.1016/j.jconrel.2008.04.013 · Cited by 1,278 · see citing works
Physical stimuli-responsive polymeric micelles for anti-cancer drug delivery
Rapoport, N. (2007) · Progress in Polymer Science · doi:10.1016/j.progpolymsci.2007.05.009 · Cited by 1,002 · see citing works
Self-citationRole of integrated cancer nanomedicine in overcoming drug resistance
Iyer, A. K., Singh, A., Ganta, S., & Amiji, M. M. (2013) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2013.07.012 · Cited by 343 · see citing works
Recent Advances in Nanomicelles Delivery Systems.
Tawfik, S. M., Azizov, S., Elmasry, M. R., Sharipov, M., & Lee, Y.-I. (2020) · Nanomaterials · doi:10.3390/nano11010070 · Cited by 156 · see citing works
“9 nm (fluorescently labeled Pluronic micelles) loaded with DOX was studied by Gao and coworkers in ovarian cancer [208].”
BackgroundDistribution kinetics of a micelle-forming block copolymer Pluronic P85
Batrakova, E. V., Li, S., Li, Y., Alakhov, V. Y., Elmquist, W. F., & Kabanov, A. V. (2004) · Journal of Controlled Release · doi:10.1016/j.jconrel.2004.09.002 · Cited by 121 · see citing works
Ultrasonically triggered drug delivery: Breaking the barrier
Husseini, G. A., Pitt, W. G., & Martins, A. M. (2014) · Colloids and Surfaces B: Biointerfaces · doi:10.1016/j.colsurfb.2014.07.051 · Cited by 87 · see citing works
Ultrasonic-activated micellar drug delivery for cancer treatment
Husseini, G. A., & Pitt, W. G. (2009) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.21444 · Cited by 83 · see citing works
WANG, Y., LI, Y., WANG, Q., WU, J., & FANG, X. (2008) · YAKUGAKU ZASSHI · doi:10.1248/yakushi.128.941 · Cited by 29 · see citing works
- Authors
- Gao, Z., Fain, H. D., & Rapoport, N.
- Affiliations
- University of Utah (US)
- Corresponding author
- Rapoport, Natalya
- ORCID
- Gao, Zhonggao
- Venue
- Molecular Pharmaceutics
- Publisher
- American Chemical Society (ACS)
- Published
- 2004-06-02
- Volume
- 1
- Issue
- 4
- Pages
- 317-330
- ISSN
- 1543-8384 (ISSN-L)
- 1543-8392
- PMC
- PMC1351321
- OpenAlex
- W2087045033
- Cited by
- 121
- References
- 32
- Citations by year
- 2026: 1 · 2025: 2 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 6 · 2015: 5 · 2014: 10 · 2013: 8 · 2012: 7
- FWCI
- 4.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Pharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Biomedical Imaging and Bioengineering (R01 EB1033, R01EB001033)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Keywords
- ultrasound-triggered drug release, polymeric micelles, tumor targeting, tissue distribution, ovarian cancer, sonication, targeted drug delivery
- MeSH terms
- Animals, Carcinoma, Drug Carriers, Feasibility Studies, Female, Flow Cytometry, Injections, Intraperitoneal, Injections, Intravenous, Male, Mice, Nude, Micelles, Neoplasm Transplantation, Neoplasms, Ovarian Neoplasms, Polymers, Ultrasonic Therapy, Drug Delivery Systems, Cell Line, Tumor, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
