Lipoproteins tethered dendrimeric nanoconstructs for effective targeting to cancer cells
Source abstract
Abstract
In the present investigation, poly (propylene imine) dendrimers up to fifth generation (PPI G5.0) were synthesized using ethylene diamine and acrylonitrile. Lipoproteins (high-density lipoprotein; HDL and low-density lipoprotein; LDL) were isolated from human plasma by discontinuous density gradient ultracentrifugation, characterized and tethered to G5.0 PPI dendrimers to construct LDL- and HDL-conjugated dendrimeric nanoconstructs for tumor-specific delivery of docetaxel. Developed formulations showed sustained release characteristics in in vitro drug release and in vivo pharmacokinetic studies. The cancer targeting potential of lipoprotein coupled dendrimers was investigated by ex vivo cytotoxicity and cell uptake studies using human hepatocellular carcinoma cell lines (HepG2 cells) and biodistribution studies in albino rats of Sprague–Dawley strain. Lipoprotein anchored dendrimeric nanoconstructs showed significant uptake by cancer cells as well as higher biodistribution of docetaxel to liver and spleen. It is concluded that these precisely synthesized engineered dendrimeric nanoconstructs could serve as promising drug carrier for fighting with the fatal disease, i.e., cancer, attributed to their defined targeting and therapeutic potential.
Source: openaire · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Dendrimers and Hyperbranched Polymers · RNA Interference and Gene Delivery · Cancer, Lipids, and Metabolism
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (38)
Show source-provided references
1. Agarwal A, Gupta U, Asthana A, Jain NK (2009) Dextran conjugated dendritic nanoconstructs as potential vectors for anti-cancer agent. Biomaterials 30:3588–359610.1016/j.biomaterials.2009.03.016 ↗
2. Agashe HB, Dutta T, Garg M, Jain NK (2006) Investigations on the toxicological profile of functionalized fifth-generation poly (propylene imine) dendrimer. J Pharm Pharmacol 58:1491–149810.1211/jpp.58.11.0010 ↗
3. Agrawal U, Mehra NK, Gupta U, Jain NK (2013) Hyperbranched dendritic nano-carriers for topical delivery of dithranol. J Drug Target. doi: 10.3109/1061186X.2013.771778
4. Asthana A, Chauhan AS, Diwan PV, Jain NK (2005) Poly (amidoamine) (PAMAM) dendritic nanostructures for controlled site specific delivery of acidic anti-inflammatory active ingredient. AAPS Pharm Sci Tech 6:536–54210.1208/pt060367 ↗
5. Bagari R, Bansal D, Gulbake A, Jain A, Soni V, Jain SK (2010) Chondroitin sulfate functionalized liposomes for solid tumor targeting. J Drug Target 19:251–25710.3109/1061186X.2010.492525 ↗
6. Bhadra D, Bhadra S, Jain S, Jain NK (2005) A PEGylated dendritic nanoparticulate carrier of fluorouracil. Int J Pharm 257:111–12410.1016/S0378-5173(03)00132-7 ↗
7. Cadenas C, Vosbeck S, Hein EM, Hellwig B, Langer A, Hayen H, Franckenstein D, Büttner B, Hammad S, Marchan R, Hermes M, Selinski S, Rahnenführer J, Peksel B, Török Z, Vígh L, Hengstler JG (2012) Glycerophospholipid profile in oncogene-induced senescence. Biochim Biophys Acta 1821:1256–126810.1016/j.bbalip.2011.11.008 ↗
8. Chen L, Sha X, Jiang X, Chen Y, Ren Q, Fang X (2013) Pluronic P105/F127 mixed micelles for the delivery of docetaxel against Taxol-resistant non-small cell lung cancer: optimization and in vitro, in vivo evaluation. Int J Nanomed 8:73–84
9. Clarke SJ, Rivory LP (1999) Clinical pharmacokinetics of DTX. Clin Pharmacokinet 36:99–11410.2165/00003088-199936020-00002 ↗
10. Corbin IR, Chen J, Cao W, Li H, Lund-Katz S, Zheng G (2007) Enhanced cancer-targeted delivery using engineered high density lipoprotein based nanocarriers. J Biomed Nanotechnol 3:367–37610.1166/jbn.2007.053 ↗
11. Dong J, Guo H, Yang R, Li H, Wang S, Zhang J, Chen W (2011) Serum LDL- and HDL-cholesterol determined by ultracentrifugation and HPLC. J Lipid Res 52:383–38810.1194/jlr.D008979 ↗
12. Dong J, Guo H, Yang R, Li H, Wang S, Zhang J, Zhou W, Chen W (2012) A novel and precise method for simultaneous measurement of serum HDL and LDL subfractions and lipoprotein (a) cholesterol by ultracentrifugation and high-performance liquid chromatography. Clin Chim Acta 413:1071–107610.1016/j.cca.2012.02.022 ↗
13. Gajbhiye V, Jain NK (2011) The treatment of Glioblastoma Xenografts by surfactant conjugated dendritic nano-conjugates. Biomaterials 32:6213–622510.1016/j.biomaterials.2011.04.057 ↗
14. Gajbhiye V, Ganesh N, Barve J, Jain NK (2013) Synthesis, characterization and targeting potential of zidovudine loaded sialic acid conjugated-mannosylated poly(propyleneimine) dendrimers. Eur J Pharm Sci 48:668–67910.1016/j.ejps.2012.12.027 ↗
15. Gupta U, Dwivedi SKD, Bid HK, Konwar R, Jain NK (2010) Ligand anchored dendrimers based nanoconstructs for effective targeting to cancer cells. Int J Pharm 393:185–19610.1016/j.ijpharm.2010.04.002 ↗
16. Houghton P (2007) The sulphorhodamine (SRB) assay and other approaches to testing plant extracts and derived compounds for activities related to reputed anticancer activity. Methods 42:377–38710.1016/j.ymeth.2007.01.003 ↗
17. Jain A, Agarwal A, Majumder S, Lariya N, Khaya A, Agrawal H, Majumdar S, Agrawal GP (2010a) Mannosylated solid lipid nanoparticles as vectors for site-specific delivery of an anti-cancer drug. J Control Rel 148:359–36710.1016/j.jconrel.2010.09.003 ↗
18. Jain K, Kesharwani P, Gupta U, Jain NK (2010b) Dendrimer toxicity: let’s meet the challenge. Int J Pharm 394:122–14210.1016/j.ijpharm.2010.04.027 ↗
19. Jia J, Xiao Y, Liu J, Zhang W, He H, Chen L, Zhang M (2012) Preparation, characterizations, and in vitro metabolic processes of paclitaxel-loaded discoidal recombinant high-density lipoproteins. J Pharm Sci 101:2900–290810.1002/jps.23210 ↗
20. Kader A, Pater A (2002) Loading anticancer drugs into HDL as well as LDL has little affect on properties of complexes and enhances cytotoxicity to human carcinoma cells. J Control Rel 80:29–4410.1016/S0168-3659(01)00536-3 ↗
21. Lo ST, Kumar A, Hsieh JT, Sun X (2013) Dendrimer nanoscaffolds for potential theranostics of prostate cancer with a focus on radiochemistry. Mol Pharm 10:793–81210.1021/mp3005325 ↗
22. Lodhi N, Mehra NK, Jain NK (2013) Development and characterization of dexamethasone mesylate anchored on multi walled carbon nanotubes. J Drug Target 21(1):67–7610.3109/1061186X.2012.729213 ↗
23. Moura JA, Valduga CJ, Tavares ER, Kretzer IF, Maria DA, Maranhao RC (2011) Novel formulation of a methotrexate derivative with a lipid nanoemulsion. Int J Nanomed 6:2285–2295
24. Ng KK, Lovell JF, Zheng G (2011) Lipoprotein inspired nanoparticles for cancer theranostics. Acc Chem Res 44:1105–111310.1021/ar200017e ↗
25. Oda MN, Hargreaves PL, Beckstead JA, Redmond KA, van Antwerpen R, Ryan RO (2006) Reconstituted high density lipoprotein enriched with the polyene antibiotic amphotericin B. J Lipid Res 47:260–26710.1194/jlr.D500033-JLR200 ↗
26. Oliveira JM, Salgado AJ, Sousa N, Mano JF, Reis RL (2010) Dendrimers and derivatives as a potential therapeutic tool in regenerative medicine strategies-a review. Prog Polym Sci 35:1163–119410.1016/j.progpolymsci.2010.04.006 ↗
27. Opitz AW, Czymmek KJ, Wickstrom E, Wagner NJ (2013) Uptake, efflux, and mass transfer coefficient of fluorescent PAMAM dendrimers into pancreatic cancer cells. Biochim Biophys Acta 1828:294–30110.1016/j.bbamem.2012.09.016 ↗
28. Patel SK, Gajbhiye V, Jain NK (2012) Synthesis, characterization and brain targeting potential of paclitaxel loaded thiamine-PPI nanoconjugates. J Drug Target 20:841–84910.3109/1061186X.2012.719231 ↗
29. Perrot G, Langlois B, Devy J, Jeanne A, Verzeaux L, Almagro S, Sartelet H, Hachet C, Schneider C, Sick E, David M, Khrestchatisky M, Emonard H, Martiny L, Dedieu S (2012) LRP-1–CD44, a new cell surface complex regulating tumor cell adhesion. Mol Cell Biol 32:3293–330710.1128/MCB.00228-12 ↗
30. Pinzon-Daza M, Garzon R, Couraud P, Romero IA, Weksler B, Ghigo D, Bosia A, Riganti C (2012) The association of statins plus LDL receptor-targeted liposome-encapsulated doxorubicin increases in vitro drug delivery across blood-brain barrier cells. Br J Pharmacol 167:1431–144710.1111/j.1476-5381.2012.02103.x ↗
31. Pires LA, Hegg R, Freitas ER, Tavares ER, Almeida CP, Baracat EC, Maranhão RC (2012) Effect of neoadjuvant chemotherapy on low-density lipoprotein (LDL) receptor and LDL receptor-related protein 1 (LRP-1) receptor in locally advanced breast cancer. Braz J Med Biol Res 45:557–56410.1590/S0100-879X2012007500068 ↗
32. Saleh EM, El-Awady RA, Anis N (2013) Predictive markers for the response to 5-fluorouracil therapy in cancer cells: Constant-field gel electrophoresis as a tool for prediction of response to 5-fluorouracil-based chemotherapy. Oncol Lett 5:321–32710.3892/ol.2012.965 ↗
33. She W, Luo K, Zhang C, Wang G, Geng Y, Li L, He B, Gu Z (2013) The potential of self-assembled, pH-responsive nanoparticles of mPEGylated peptide dendron-doxorubicin conjugates for cancer therapy. Biomaterials 34:1613–162310.1016/j.biomaterials.2012.11.007 ↗
34. Singh R, Mehra NK, Jain V, Jain NK (2013) Gemcitabine-loaded smart carbon nanotubes for effective targeting to cancer cell. J Drug Target. doi: 0.3109/1061186X.2013.778264
35. Szulc A, Appelhans D, Voit B, Bryszewska M, Klajnert B (2013) Studying complexes between PPI dendrimers and Mant-ATP. J Fluoresc 23:349–35610.1007/s10895-012-1153-y ↗
36. Wang MD, Kiss RS, Franklin V, McBride HM, Whitman SC, Marcel YL (2007) Different cellular traffic of LDL-cholesterol and acetylated LDL-cholesterol leads to distinct reverse cholesterol transport pathways. J Lipid Res 48:633–64510.1194/jlr.M600470-JLR200 ↗
37. Webster DM, Sundaram P, Byrne ME (2013) Injectable nanomaterials for drug delivery: carriers, targeting moieties, and therapeutics. Euro J Pharm Biopharm. doi: 10.1016/j.ejpb.2012.12.009
38. Zhao L, Wei YM, Zhong XD, Liang Y, Zhang XM, Li W (2009) PK and tissue distribution of DTX in rabbits after i.v. administration of liposomal and injectable formulations. J Pharm Biomed Anal 49:989–99610.1016/j.jpba.2009.01.016 ↗