Enkephalin loaded and RGD decorated PLGA–poloxamer nanoparticles for effective targeting in cancer cells
Source abstract
Abstract
Enkephalins have been shown to retard cell proliferation in various human cancer cell lines, including breast, soft tissue, gastrointestinal, brain, pancreatic, and liver cell cultures. In this study, we have synthesized polymeric PLGA [poly (lactide-co-glycolic acid)]–poloxamer nanoparticles loaded with enkephalins in order to achieve a consistent release of these neuropeptides. In order to provide targeting abilities toward cancerous cells, these nanoparticles were functionalized with RGD (Arg-Gly-Asp-amide, a cancer cell marker). The synthesized nanoparticles (NPs) were further thoroughly characterized for biological activity including cytotoxicity, anticancer activity as well as cancer cell uptake abilities. Interestingly, it was observed that the fluorescent marker containing cancer cell-targeting peptide (RGD) conjugated nano-formulation(s) exhibited good uptake and internalization into cancer cells. The results indicate that the developed enkephalin-RGD-PLGA nanoparticles can serve as suitable targeted drug delivery vehicle/system for existing conventional drugs as well as in increasing the efficacy of drugs.
Source: expertdata · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Neuropeptides and Animal Physiology · Supramolecular Self-Assembly in Materials · Advanced Drug Delivery Systems
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (38)
Show source-provided references
1. Mongi-Bragato B, Avalos MP, Guzmán AS et al (2018) Enkephalin as a pivotal player in neuroadaptations related to psychostimulant addiction. Front Psych. https://doi.org/10.3389/fpsyt.2018.0022210.3389/fpsyt.2018.00222 ↗
2. Xu H, Shi X, Li X et al (2020) Neurotransmitter and neuropeptide regulation of mast cell function: a systematic review. J Neuroinflammation 17:356–371. https://doi.org/10.1186/s12974-020-02029-310.1186/s12974-020-02029-3 ↗
3. Yeo XY, Cunliffe G, Ho RC et al (2022) Potentials of neuropeptides as therapeutic agents for neurological diseases. Biomedicines 10:343–370. https://doi.org/10.3390/biomedicines1002034310.3390/biomedicines10020343 ↗
4. Neugebauer V, Mazzitelli M, Cragg B et al (2020) Amygdala, neuropeptides, and chronic pain-related affective behaviors. Neuropharmacology 170:108052–108115. https://doi.org/10.1016/j.neuropharm.2020.10805210.1016/j.neuropharm.2020.108052 ↗
5. Palmer CB, Meyrath M, Canals M et al (2022) Atypical opioid receptors: unconventional biology and therapeutic opportunities. Pharmacol Ther 233:108014–108029. https://doi.org/10.1016/j.pharmthera.2021.10801410.1016/j.pharmthera.2021.108014 ↗
6. Wang R, Zhang Y, Shan F (2019) Interaction of opioid growth factor (OGF) and opioid antagonist and their significance in cancer therapy. Int Immunopharmacol 75:105785. https://doi.org/10.1016/j.intimp.2019.10578510.1016/j.intimp.2019.105785 ↗
7. Wang X, Jiao X, Meng Y et al (2018) Methionine enkephalin (MENK) inhibits human gastric cancer through regulating tumor associated macrophages (TAMs) and PI3K/AKT/mTOR signaling pathway inside cancer cells. Int Immunopharmacol 65:312–322. https://doi.org/10.1016/j.intimp.2018.10.02310.1016/j.intimp.2018.10.023 ↗
8. Huang H, Liu B, Qu N et al (2021) Research progress of opioid growth factor in immune-related diseases and cancer diseases. Int Immunopharmacol 99:107713–107723. https://doi.org/10.1016/j.intimp.2021.10771310.1016/j.intimp.2021.107713 ↗
9. Wang X, Tian J, Jiao X et al (2018) The novel mechanism of anticancer effect on gastric cancer through inducing G0/G1 cell cycle arrest and caspase-dependent apoptosis in vitro and in vivo by methionine enkephalin. Cancer Manag Res 10:4773–4787. https://doi.org/10.2147/CMAR.S17834310.2147/CMAR.S178343 ↗
10. Wang D-M, Wang G-C, Yang J et al (2016) Inhibition of the growth of human melanoma cells by methionine enkephalin. Mol Med Rep 14:5521–5527. https://doi.org/10.3892/mmr.2016.594110.3892/mmr.2016.5941 ↗
11. Bai X, Cao X, Qu N et al (2021) Methionine enkephalin activates autophagy and stimulates tumour cell immunogenicity in human cutaneous squamous cell carcinoma. Int Immunopharmacol 96:107733–107745. https://doi.org/10.1016/j.intimp.2021.10773310.1016/j.intimp.2021.107733 ↗
12. Lueptow LM, Fakira AK, Bobeck EN (2018) The contribution of the descending pain modulatory pathway in opioid tolerance. Front Neurosci. https://doi.org/10.3389/fnins.2018.0088610.3389/fnins.2018.00886 ↗
13. Kumar M, Pandey RS, Patra KC et al (2013) Evaluation of neuropeptide loaded trimethyl chitosan nanoparticles for nose to brain delivery. Int J Biol Macromol 61:189–195. https://doi.org/10.1016/j.ijbiomac.2013.06.04110.1016/j.ijbiomac.2013.06.041 ↗
14. Komatsu T, Katsuyama S, Mizoguchi H et al (2014) Spinal ERK2 activation through δ2-opioid receptors contributes to nociceptive behavior induced by intrathecal injection of leucine-enkephalin. Peptides (NY) 54:131–139. https://doi.org/10.1016/j.peptides.2014.01.01410.1016/j.peptides.2014.01.014 ↗
15. Budka J, Kowalski S, Chylinska M et al (2021) Opioid growth factor and its derivatives as potential non-toxic multifunctional anticancer and analgesic compounds. Curr Med Chem 28:673–686. https://doi.org/10.2174/092986732766620030412240610.2174/0929867327666200304122406 ↗
16. Shechter Y, Tsubery H, Mironchik M et al (2005) Reversible PEGylation of peptide YY 3–36 prolongs its inhibition of food intake in mice. FEBS Lett 579:2439–2444. https://doi.org/10.1016/j.febslet.2005.03.04410.1016/j.febslet.2005.03.044 ↗
17. Shechter Y, Mironchik M, Saul A et al (2007) New technologies to prolong life-time of peptide and protein drugs in vivo. Int J Pept Res Ther 13:105–117. https://doi.org/10.1007/s10989-006-9052-110.1007/s10989-006-9052-1 ↗
18. Shechter Y, Heldman E, Sasson K et al (2010) Delivery of neuropeptides from the periphery to the brain: studies with enkephalin. ACS Chem Neurosci 1:399–406. https://doi.org/10.1021/cn100001j10.1021/cn100001j ↗
19. Uchegbu IF, Carlos M, McKay C et al (2014) Chitosan amphiphiles provide new drug delivery opportunities. Polym Int 63:1145–1153. https://doi.org/10.1002/pi.472110.1002/pi.4721 ↗
20. Malatesta M, Galimberti V, Cisterna B et al (2014) Chitosan nanoparticles are efficient carriers for delivering biodegradable drugs to neuronal cells. Histochem Cell Biol 141:551–558. https://doi.org/10.1007/s00418-013-1175-910.1007/s00418-013-1175-9 ↗
21. Kim GC, Cheon DH, Lee Y (2021) Challenge to overcome current limitations of cell-penetrating peptides. Biochim Biophys Acta (BBA) Proteins Proteom 1869:140604–140624. https://doi.org/10.1016/j.bbapap.2021.14060410.1016/j.bbapap.2021.140604 ↗
22. Jafari B, Pourseif MM, Barar J et al (2019) Peptide-mediated drug delivery across the blood-brain barrier for targeting brain tumors. Expert Opin Drug Deliv 16:583–605. https://doi.org/10.1080/17425247.2019.161491110.1080/17425247.2019.1614911 ↗
23. Newman MR, Benoit DSW (2018) In vivo translation of peptide-targeted drug delivery systems discovered by phage display. Bioconjug Chem 29:2161–2169. https://doi.org/10.1021/acs.bioconjchem.8b0028510.1021/acs.bioconjchem.8b00285 ↗
24. Hoppenz P, Els-Heindl S, Beck-Sickinger AG (2020) Peptide-drug conjugates and their targets in advanced cancer therapies. Front Chem. https://doi.org/10.3389/fchem.2020.0057110.3389/fchem.2020.00571 ↗
25. Islam Y, Leach AG, Smith J et al (2020) Peptide based drug delivery systems to the brain. Nano Express 1:12002–12026. https://doi.org/10.1088/2632-959X/ab900810.1088/2632-959X/ab9008 ↗
26. Szweda R, Trzebicka B, Dworak A et al (2016) Smart Polymeric Nanocarriers of Met-enkephalin. Biomacromolecules 17:2691–2700. https://doi.org/10.1021/acs.biomac.6b0072510.1021/acs.biomac.6b00725 ↗
27. Ansari R, Sadati SM, Mozafari N et al (2020) Carbohydrate polymer-based nanoparticle application in drug delivery for CNS-related disorders. Eur Polym J 128:109607–109621. https://doi.org/10.1016/j.eurpolymj.2020.10960710.1016/j.eurpolymj.2020.109607 ↗
28. Godfrey L, Iannitelli A, Garrett NL et al (2018) Nanoparticulate peptide delivery exclusively to the brain produces tolerance free analgesia. J Control Release 270:135–144. https://doi.org/10.1016/j.jconrel.2017.11.04110.1016/j.jconrel.2017.11.041 ↗
29. Zhang L, Li G, Gao M et al (2016) RGD-peptide conjugated inulin-ibuprofen nanoparticles for targeted delivery of Epirubicin. Colloids Surf B 144:81–89. https://doi.org/10.1016/j.colsurfb.2016.03.07710.1016/j.colsurfb.2016.03.077 ↗
30. Fotakis G, Timbrell JA (2006) In vitro cytotoxicity assays: comparison of LDH, neutral red, MTT and protein assay in hepatoma cell lines following exposure to cadmium chloride. Toxicol Lett 160:171–177. https://doi.org/10.1016/j.toxlet.2005.07.00110.1016/j.toxlet.2005.07.001 ↗
31. Liang H, Jin C, Tang Y et al (2014) Cytotoxicity of silica nanoparticles on HaCaT cells. J Appl Toxicol 34:367–372. https://doi.org/10.1002/jat.295310.1002/jat.2953 ↗
32. Sapsford KE, Tyner KM, Dair BJ et al (2011) Analyzing nanomaterial bioconjugates: a review of current and emerging purification and characterization techniques. Anal Chem 83:4453–4488. https://doi.org/10.1021/ac200853a10.1021/ac200853a ↗
33. Chaganti LK, Venkatakrishnan N, Bose K (2018) An efficient method for FITC labelling of proteins using tandem affinity purification. Biosci Rep. https://doi.org/10.1042/BSR2018176410.1042/BSR20181764 ↗
34. Surugau N, Urban PL (2009) Electrophoretic methods for separation of nanoparticles. J Sep Sci 32:1889–1906. https://doi.org/10.1002/jssc.20090007110.1002/jssc.200900071 ↗
35. Pyell U (2010) Characterization of nanoparticles by capillary electromigration separation techniques. Electrophoresis 31:814–831. https://doi.org/10.1002/elps.20090055510.1002/elps.200900555 ↗
36. Danhier F, Ansorena E, Silva JM et al (2012) PLGA-based nanoparticles: an overview of biomedical applications. J Control Release 161:505–522. https://doi.org/10.1016/j.jconrel.2012.01.04310.1016/j.jconrel.2012.01.043 ↗
37. Gu J-H, Ge J-B, Li M et al (2013) Poloxamer 188 protects neurons against ischemia/reperfusion injury through preserving integrity of cell membranes and blood brain barrier. PLoS ONE 8:e61641–61652. https://doi.org/10.1371/journal.pone.006164110.1371/journal.pone.0061641 ↗
38. Javed R, Zia M, Naz S et al (2020) Role of capping agents in the application of nanoparticles in biomedicine and environmental remediation: recent trends and future prospects. J Nanobiotechnol 18:172–187. https://doi.org/10.1186/s12951-020-00704-410.1186/s12951-020-00704-4 ↗