Image-Based Quantification of Gold Nanoparticle Uptake and Localization in 3D Tumor Models to Inform Radiosensitization Schedule.
| Title: | Image-Based Quantification of Gold Nanoparticle Uptake and Localization in 3D Tumor Models to Inform Radiosensitization Schedule. |
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| Authors: | Petrovic LZ; Department of Physics, University of Massachusetts at Boston, Boston, MA 02125, USA.; Oumano M; Medical Physics Program, Department of Physics and Applied Physics, University of Massachusetts Lowell, Lowell, MA 02125, USA.; Hanlon J; ZEISS Group, Carl Zeiss Meditec, Inc., Dublin, CA 94568, USA.; Arnoldussen M; ZEISS Group, Carl Zeiss Meditec, Inc., Dublin, CA 94568, USA.; Koruga I; ZEISS Group, Carl Zeiss Meditec, Inc., Dublin, CA 94568, USA.; Yasmin-Karim S; Dana-Farber/Harvard Cancer Center, Boston, MA 02215, USA.; Ngwa W; Medical Physics Program, Department of Physics and Applied Physics, University of Massachusetts Lowell, Lowell, MA 02125, USA.; Dana-Farber/Harvard Cancer Center, Boston, MA 02215, USA.; Department of Radiation Oncology, Johns Hopkins University, Washington, DC 20016, USA.; Celli J; Department of Physics, University of Massachusetts at Boston, Boston, MA 02125, USA. |
| Source: | Pharmaceutics [Pharmaceutics] 2022 Mar 18; Vol. 14 (3). Date of Electronic Publication: 2022 Mar 18. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101534003 Publication Model: Electronic Cited Medium: Print ISSN: 1999-4923 (Print) Linking ISSN: 19994923 NLM ISO Abbreviation: Pharmaceutics Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Original Publication: Basel, Switzerland : MDPI |
| Abstract: | Gold nanoparticles (GNPs) have shown particular promise as radiosensitizing agents and as complementary drug delivery agents to improve therapeutic index in cancer treatment. Optimal implementation, however, depends critically on the localization of GNPs at the time of irradiation, which, in turn, depends on their size, shape, and chemical functionalization, as well as organism-level pharmacokinetics and interactions with the tumor microenvironment. Here, we use in vitro 3D cultures of A549 lung carcinoma cells, which recapitulate interaction with extracellular matrix (ECM) components, combined with quantitative fluorescence imaging to study how time-dependent localization of ultrasmall GNPs in tumors and ECM impacts the degree of damage enhancement to tumor cells. Confocal imaging of fluorescence-labeled GNPs in 3D culture reveals that nanoparticles are initially embedded in ECM and only gradually accumulate in cancer cells over multiple days. Furthermore, the timing of GNP redistribution from ECM to cellular compartments directly impacts efficacy, with major damage enhancement when irradiation is performed after GNPs have accumulated significantly in 3D tumor nodules. These results underscore the importance of the timing and scheduling in treatment planning to ensure optimal radiosensitization, as well as the necessity of studying these effects in model systems that recapitulate elements of tumor microenvironment interaction. |
| References: | Sci Rep. 2016 Jan 20;6:19442. (PMID: 26787230); J Biomed Opt. 2010 Sep-Oct;15(5):051603. (PMID: 21054077); Nano Lett. 2015 Nov 11;15(11):7488-96. (PMID: 26418302); Nat Nanotechnol. 2011 Apr 24;6(6):385-91. (PMID: 21516092); Br J Radiol. 2012 Feb;85(1010):101-13. (PMID: 22010024); CA Cancer J Clin. 2021 Jan;71(1):7-33. (PMID: 33433946); Phys Med Biol. 2016 Dec 21;61(24):N697-N707. (PMID: 27910826); Crit Rev Oncol Hematol. 2000 Nov-Dec;36(2-3):193-207. (PMID: 11033306); Front Oncol. 2017 Sep 19;7:208. (PMID: 28971063); Nat Nanotechnol. 2010 Jun;5(6):465-72. (PMID: 20383126); Sci Rep. 2014 Jan 17;4:3751. (PMID: 24435043); Front Oncol. 2018 Mar 12;8:56. (PMID: 29594038); Nat Nanotechnol. 2007 Dec;2(12):751-60. (PMID: 18654426); Nanomaterials (Basel). 2019 Feb 19;9(2):. (PMID: 30791480); Phys Med Biol. 2004 Sep 21;49(18):N309-15. (PMID: 15509078); Int J Radiat Oncol Biol Phys. 2011 Feb 1;79(2):531-9. (PMID: 21095075); ACS Nano. 2012 May 22;6(5):4483-93. (PMID: 22540892); Chem Sci. 2017 Mar 1;8(3):1719-1735. (PMID: 28451297); Future Oncol. 2014 May;10(7):1311-27. (PMID: 24947267); Toxicol Lett. 2008 Jun 30;179(2):78-84. (PMID: 18502058); Int J Nanomedicine. 2020 Nov 24;15:9407-9430. (PMID: 33262595); J Natl Cancer Inst. 2010 Apr 7;102(7):448-50. (PMID: 20339135); Sci Rep. 2017 Mar 16;7:44752. (PMID: 28300190); Nat Protoc. 2006;1(5):2315-9. (PMID: 17406473); Int J Radiat Oncol Biol Phys. 2015 Feb 1;91(2):385-92. (PMID: 25482302); Theranostics. 2012;2(9):827-39. (PMID: 23082096); Cancer Nanotechnol. 2017;8(1):2. (PMID: 28217176); Nanomedicine (Lond). 2014 May;9(7):1063-82. (PMID: 24978464); Theranostics. 2018 Feb 12;8(7):1824-1849. (PMID: 29556359); Adv Mater. 2007;19:3136-3141. (PMID: 19020672); Transl Cancer Res. 2013 Aug;2(4):. (PMID: 24392307); Phys Med Biol. 2015 Sep 21;60(18):7035-43. (PMID: 26309064) |
| Grant Information: | R00 CA155045 United States CA NCI NIH HHS; R01 CA239042 United States CA NCI NIH HHS; R00CA155045 to JPC, and R01CA239042 to WN United States NH NIH HHS |
| Contributed Indexing: | Keywords: 3D tumor models; cancer; nanoparticles; pharmacokinetics; radiosensitization |
| Entry Date(s): | Date Created: 20220326 Latest Revision: 20230301 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC8953383 |
| DOI: | 10.3390/pharmaceutics14030667 |
| PMID: | 35336040 |
| Database: | MEDLINE |
Journal Article