Glycol chitosan amphiphile nanotheranostic system for ultrasound-mediated localized release and biodistribution of doxorubicin
Source abstract
Abstract
Ultrasound-mediated delivery has garnered attention as a noninvasive modality for localized drug delivery in cancer. Doxorubicin, a chemotherapeutic drug, shows low penetration, nonspecific distribution, and uncontrolled release. We have synthesized a hydrophobic doxorubicin (hDox)-loaded palmitoyl-modified glycol chitosan amphiphile (PmGCA) polymer-based nanotheranostic drug delivery system (hDox-NDS) for ultrasound (US)-mediated release. PmGCA encapsulates 210 μg/mL hDox in 90 ± 15 nm cationic micelles. The reappearance of the Dox fluorescence peak after 2 MHz US exposure confirms the encapsulated drug release. hDox-NDS display a considerable drug release (~30 to 50%) over 72 h, following the Weibull model. Fluorescence microscopy shows a higher uptake of hDox-NDS (~10%) in rhabdomyosarcoma (RD) cells compared to DoxHCl. Ultrasound exposure significantly (p < 0.001) enhances the anticancer effect of hDox-NDS on RD cells, as shown by its lower IC50 value of 1.7 ± 0.05 μM compared to that of DoxHCl (2.62 ± 1.2 μM). In vivo optical imaging shows significantly lower fluorescence in the heart (~84%) and liver (~59%) compared to DoxHCl, thereby reducing side effects. This nanotheranostic hDox-NDS has been considered an effective drug delivery system, offering enhanced therapeutic effects in cancer treatment.
Source: expertdata · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Ultrasound and Hyperthermia Applications · Nanoparticle-Based Drug Delivery · Nanoplatforms for cancer theranostics
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (59)
Show source-provided references
1. Ladju RB, Ulhaq ZS, Soraya GV (2022) Nanotheranostics: a powerful next-generation solution to tackle hepatocellular carcinoma. World J Gastroenterol 28:17610.3748/wjg.v28.i2.176 ↗
2. Afadzi M, Myhre OF, Yemane PT et al (2020) Effect of acoustic radiation force on the distribution of nanoparticles in solid tumors. IEEE Trans Ultrason Ferroelectr Freq Control 68:432–44510.1109/TUFFC.2020.3027072 ↗
3. Kim D, Lee JH, Moon H et al (2021) Development and evaluation of an ultrasound-triggered microbubble combined transarterial chemoembolization (TACE) formulation on rabbit VX2 liver cancer model. Theranostics 11:7910.7150/thno.45348 ↗
4. Young RC, Ozols RF, Myers CE (1981) The anthracycline antineoplastic drugs. N Engl J Med 305:139–15310.1056/NEJM198107163050305 ↗
5. Melim C, Magalhães M, Santos AC et al (2022) Nanoparticles as phytochemical carriers for cancer treatment: news of the last decade. Expert Opin Drug Deliv 19:179–19710.1080/17425247.2022.2041599 ↗
6. Gabizon A, Shmeeda H, Barenholz Y (2003) Pharmacokinetics of pegylated liposomal doxorubicin. Clin Pharmacokinet 42:419–43610.2165/00003088-200342050-00002 ↗
7. Hekmatirad S, Moloudizargari M, Moghadamnia AA et al (2021) Inhibition of exosome release sensitizes U937 cells to PEGylated liposomal doxorubicin. Front Immunol 12:200810.3389/fimmu.2021.692654 ↗
8. Hilger RA, Richly H, Grubert M et al (2005) Pharmacokinetics (PK) of a liposomal encapsulated fraction containing doxorubicin and of doxorubicin released from the liposomal capsule after intravenous infusion of Caelyx/Doxil. Int J Clin Pharmacol Ther 43:588–58910.5414/CPP43588 ↗
9. Liu L, Kshirsagar PG, Gautam SK et al (2022) Nanocarriers for pancreatic cancer imaging, treatments, and immunotherapies. Theranostics 12:103010.7150/thno.64805 ↗
10. Entzian K, Aigner A (2021) Drug delivery by ultrasound-responsive nanocarriers for cancer treatment. Pharmaceutics 13:113510.3390/pharmaceutics13081135 ↗
11. Mohan P, Rapoport N (2010) Doxorubicin as a molecular nanotheranostic agent: effect of doxorubicin encapsulation in micelles or nanoemulsions on the ultrasound-mediated intracellular delivery and nuclear trafficking. Mol Pharm 7:1959–197310.1021/mp100269f ↗
12. Mi P (2020) Stimuli-responsive nanocarriers for drug delivery, tumor imaging, therapy and theranostics. Theranostics 10:455710.7150/thno.38069 ↗
13. Behera SK, Mohanty ME, Mohapatra M (2021) A fluorescence study of the interaction of anticancer drug molecule doxorubicin hydrochloride in pluronic P123 and F127 micelles. J Fluoresc 31:17–2710.1007/s10895-020-02630-y ↗
14. Afshari AR, Sanati M, Mollazadeh H et al (2022) Nanoparticle-based drug delivery systems in cancer: a focus on inflammatory pathways. Semin Cancer Biol. https://doi.org/10.1016/j.semcancer.2022.01.00810.1016/j.semcancer.2022.01.008 ↗
15. Xia H, Yang D, He W et al (2021) Ultrasound-mediated microbubbles cavitation enhanced chemotherapy of advanced prostate cancer by increasing the permeability of blood-prostate barrier. Transl Oncol 14:10117710.1016/j.tranon.2021.101177 ↗
16. Zia N, Iqbal Z, Raza A et al (2022) Glycol-chitosan-based Technetium-99m-loaded multifunctional nanomicelles: synthesis, evaluation, and in vivo biodistribution. Nanomaterials 12:2198. https://doi.org/10.3390/nano1213219810.3390/nano12132198 ↗
17. Uchegbu IF, Sadiq L, Arastoo M et al (2001) Quaternary ammonium palmitoyl glycol chitosan—a new polysoap for drug delivery. Int J Pharm 224:185–19910.1016/S0378-5173(01)00763-3 ↗
18. Lalatsa A, Schätzlein AG, Garrett NL et al (2015) Chitosan amphiphile coating of peptide nanofibres reduces liver uptake and delivers the peptide to the brain on intravenous administration. J Controlled Release 197:87–96. https://doi.org/10.1016/j.jconrel.2014.10.02810.1016/j.jconrel.2014.10.028 ↗
19. Min HS, You DG, Son S et al (2015) Echogenic glycol chitosan nanoparticles for ultrasound-triggered cancer Theranostics. Theranostics 5:1402–1418. https://doi.org/10.7150/thno.1309910.7150/thno.13099 ↗
20. Zhou X, Guo L, Shi D et al (2019) Biocompatible chitosan nanobubbles for ultrasound-mediated targeted delivery of doxorubicin. Nanoscale Res Lett 14:24. https://doi.org/10.1186/s11671-019-2853-x10.1186/s11671-019-2853-x ↗
21. Meng D, Guo L, Shi D et al (2019) Charge-conversion and ultrasound-responsive O-carboxymethyl chitosan nanodroplets for controlled drug delivery. Nanomed 14:2549–256510.2217/nnm-2019-0217 ↗
22. Kanwal U, Bukhari NI, Rana NF et al (2019) Doxorubicin-loaded quaternary ammonium palmitoyl glycol chitosan polymeric nanoformulation: uptake by cells and organs. Int J Nanomedicine 14:1–1510.2147/IJN.S176868 ↗
23. Wei T, Chen C, Liu J et al (2015) Anticancer drug nanomicelles formed by self-assembling amphiphilic dendrimer to combat cancer drug resistance. Proc Natl Acad Sci 112:2978–298310.1073/pnas.1418494112 ↗
24. Khan MA, Ansari MM, Arif ST et al (2021) Eplerenone nanocrystals engineered by controlled crystallization for enhanced oral bioavailability. Drug Deliv 28:2510–252410.1080/10717544.2021.2008051 ↗
25. Ovais M, Nadhman A, Khalil AT et al (2017) Biosynthesized colloidal silver and gold nanoparticles as emerging leishmanicidal agents: an insight. Nanomed 12:2807–281910.2217/nnm-2017-0233 ↗
26. Li K, Li P, Jia Z et al (2018) Enhanced fluorescent intensity of magnetic-fluorescent bifunctional PLGA microspheres based on Janus electrospraying for bioapplication. Sci Rep 8:1–11
27. Rehman M, Raza A, Khan JA, Zia MA (2021) Laser responsive cisplatin-gold nano-assembly synergizes the effect of cisplatin with compliance. J Pharm Sci 110:1749–176010.1016/j.xphs.2021.01.012 ↗
28. Mannaris C, Teo BM, Seth A et al (2018) Gas-stabilizing gold nanocones for acoustically mediated drug delivery. Adv Healthc Mater 7:180018410.1002/adhm.201800184 ↗
29. Sarwar U, Naeem M, Nurjis F, et al (2022) Ultrasound-mediated in vivo biodistribution of coumarin-labeled sorafenib-loaded liposome-based nanotheranostic system. Nanomed 17:1909–192710.2217/nnm-2022-0137 ↗
30. Salgarella AR, Zahoranová A, Šrámková P et al (2018) Investigation of drug release modulation from poly (2-oxazoline) micelles through ultrasound. Sci Rep 8:1–1310.1038/s41598-018-28140-3 ↗
31. Nelson TR, Fowlkes JB, Abramowicz JS, Church CC (2009) Ultrasound biosafety considerations for the practicing sonographer and sonologist. J Ultrasound Med 28:139–150. https://doi.org/10.7863/jum.2009.28.2.13910.7863/jum.2009.28.2.139 ↗
32. Schneider CA, Rasband WS, Eliceiri KW (2012) NIH Image to ImageJ: 25 years of image analysis. Nat Methods 9:671–67510.1038/nmeth.2089 ↗
33. Lefort CT, Kim M (2010) Human T lymphocyte isolation, culture and analysis of migration in vitro. JoVE J Vis Exp e201710.3791/2017-v ↗
34. Jawaid P, Rehman MU, Hassan MA et al (2016) Effect of platinum nanoparticles on cell death induced by ultrasound in human lymphoma U937 cells. Ultrason Sonochem 31:206–215. https://doi.org/10.1016/j.ultsonch.2015.12.01310.1016/j.ultsonch.2015.12.013 ↗
35. Esmaeilzadeh-Gharedaghi E, Faramarzi MA, Amini MA et al (2012) Effects of processing parameters on particle size of ultrasound prepared chitosan nanoparticles: an artificial neural networks study. Pharm Dev Technol 17:638–64710.3109/10837450.2012.696269 ↗
36. Uchegbu IF, Breznikar J, Zaffalon A et al (2021) Polymeric micelles for the enhanced deposition of hydrophobic drugs into ocular tissues, without plasma exposure. Pharmaceutics 13:74410.3390/pharmaceutics13050744 ↗
37. Gnapareddy B, Reddy Dugasani S, Ha T et al (2015) Chemical and physical characteristics of doxorubicin hydrochloride drug-doped salmon DNA thin films. Sci Rep 5:1–910.1038/srep12722 ↗
38. Huang K-Y, He H-X, He S-B et al (2019) Gold nanocluster-based fluorescence turn-off probe for sensing of doxorubicin by photoinduced electron transfer. Sens Actuators B Chem 296:12665610.1016/j.snb.2019.126656 ↗
39. Chooi KW, Carlos MIS, Soundararajan R et al (2014) Physical characterisation and long-term stability studies on quaternary ammonium palmitoyl glycol chitosan (GCPQ)—a new drug delivery polymer. J Pharm Sci 103:2296–230610.1002/jps.24026 ↗
40. Lu Y, Zhang E, Yang J, Cao Z (2018) Strategies to improve micelle stability for drug delivery. Nano Res 11:4985–4998. https://doi.org/10.1007/s12274-018-2152-310.1007/s12274-018-2152-3 ↗
41. Lu D, Wen X, Liang J et al (2009) A pH-sensitive nano drug delivery system derived from pullulan/doxorubicin conjugate. J Biomed Mater Res B Appl Biomater 89B:177–183. https://doi.org/10.1002/jbm.b.3120310.1002/jbm.b.31203 ↗
42. Choi J-S, Park J-W, Seu Y-B, Doh K-O (2021) Enhanced efficacy of folate-incorporated cholesteryl doxorubicin liposome in folate receptor abundant cancer cell. J Drug Deliv Sci Technol 62:10238510.1016/j.jddst.2021.102385 ↗
43. Wu P, Jia Y, Qu F et al (2017) Ultrasound-responsive polymeric micelles for sonoporation-assisted site-specific therapeutic action. ACS Appl Mater Interfaces 9:25706–2571610.1021/acsami.7b05469 ↗
44. Lalatsa A, Schatzlein AG, Uchegbu IF (2014) Strategies to deliver peptide drugs to the brain. Mol Pharm 11:1081–109310.1021/mp400680d ↗
45. Izci M, Maksoudian C, Manshian BB, Soenen SJ (2021) The use of alternative strategies for enhanced nanoparticle delivery to solid tumors. Chem Rev 121:1746–180310.1021/acs.chemrev.0c00779 ↗
46. Herdiana Y, Wathoni N, Shamsuddin S, Muchtaridi M (2022) Drug release study of the chitosan-based nanoparticles. Heliyon 8:e08674. https://doi.org/10.1016/j.heliyon.2021.e0867410.1016/j.heliyon.2021.e08674 ↗
47. Foroozandeh P, Aziz AA (2018) Insight into cellular uptake and intracellular trafficking of nanoparticles. Nanoscale Res Lett 13:1–1210.1186/s11671-018-2728-6 ↗
48. Snipstad S, Berg S, Mørch Ý et al (2017) Ultrasound improves the delivery and therapeutic effect of nanoparticle-stabilized microbubbles in breast cancer xenografts. Ultrasound Med Biol 43:2651–266910.1016/j.ultrasmedbio.2017.06.029 ↗
49. Xiong R, Xu RX, Huang C et al (2021) Stimuli-responsive nanobubbles for biomedical applications. Chem Soc Rev 50:5746–577610.1039/C9CS00839J ↗
50. Champion JA, Walker A, Mitragotri S (2008) Role of particle size in phagocytosis of polymeric microspheres. Pharm Res 25:1815–182110.1007/s11095-008-9562-y ↗
51. Fang C, Kievit FM, Cho Y-C et al (2012) Effect of cationic side-chains on intracellular delivery and cytotoxicity of pH sensitive polymer–doxorubicin nanocarriers. Nanoscale 4:7012–702010.1039/c2nr32159a ↗
52. Jiang LQ, Wang TY, Webster TJ et al (2017) Intracellular disposition of chitosan nanoparticles in macrophages: intracellular uptake, exocytosis, and intercellular transport. Int J Nanomedicine 12:638310.2147/IJN.S142060 ↗
53. Alqahtani MS, Syed R, Alshehri M (2020) Size-dependent phagocytic uptake and immunogenicity of gliadin nanoparticles. Polymers 12:257610.3390/polym12112576 ↗
54. Vonarbourg A, Passirani C, Saulnier P, Benoit J-P (2006) Parameters influencing the stealthiness of colloidal drug delivery systems. Biomaterials 27:4356–437310.1016/j.biomaterials.2006.03.039 ↗
55. Nittayacharn P, Yuan H-X, Hernandez C et al (2019) Enhancing tumor drug distribution with ultrasound-triggered nanobubbles. J Pharm Sci 108:3091–309810.1016/j.xphs.2019.05.004 ↗
56. Fant C, Lafond M, Rogez B et al (2019) In vitro potentiation of doxorubicin by unseeded controlled non-inertial ultrasound cavitation. Sci Rep 9:15581. https://doi.org/10.1038/s41598-019-51785-710.1038/s41598-019-51785-7 ↗
57. Liang H-D, Lu QL, Xue S-A et al (2004) Optimisation of ultrasound-mediated gene transfer (sonoporation) in skeletal muscle cells. Ultrasound Med Biol 30:1523–1529. https://doi.org/10.1016/j.ultrasmedbio.2004.08.02110.1016/j.ultrasmedbio.2004.08.021 ↗
58. Zhang Z, Wang Y, Ma Q et al (2021) Biomimetic carrier-free nanoparticle delivers digoxin and doxorubicin to exhibit synergetic antitumor activity in vitro and in vivo. Chem Eng J 406:12680110.1016/j.cej.2020.126801 ↗
59. Liu D, Mori A, Huang L (1992) Role of liposome size and RES blockade in controlling biodistribution and tumor uptake of GM1-containing liposomes. Biochim Biophys Acta BBA - Biomembr 1104:95–101. https://doi.org/10.1016/0005-2736(92)90136-A10.1016/0005-2736(92)90136-A ↗