pHe- and glutathione-stepwise-responsive polypeptide nanogel for smart and efficient drug delivery
Source abstract
Abstract
Smart drug delivery system of core–shell-type polypeptide nanogel of poly(Z-l-lysine-co-l-cystine) (PLL-LC) has been synthesized, which showed high drug loading content (DLC 16.5%) of DOX and pHe–glutathione (GSH) stepwise responsive disassembly. Modifying the shell of the nanogel by 2,3-dimethylmaleic anhydride (DMA) makes it quickly respond to the weak acidic tumor microenvironment (pHe 6.8–6.5), inducing the surface charge reversal and promoting the nanogel efficient uptake by cancer cells. Next, the nanogel can release encapsulated DOX in cytoplasm in the presence of high level of GSH therein via reduction and disassembly of the nanogel, resulting in highly selective cytotoxicity. MTT studies reveal the good biocompatibility of the nanogel before charge reversal and an efficient toxicity to cell under pHe microenvironment. In vitro experiments confirm the smart stepwise degradability of the nanogel and efficient therapy ability to cancer cell, indicating the nanogel is a potential drug delivery system.
Source: openaire · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Nanoparticle-Based Drug Delivery · Graphene and Nanomaterials Applications · Nanoplatforms for cancer theranostics
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (30)
Show source-provided references
1. Ge Z, Liu S (2013) Functional block copolymer assemblies responsive to tumor and intracellular microenvironments for site-specific drug delivery and enhanced imaging performance. Chem Soc Rev 42:7289–732510.1039/c3cs60048c ↗
2. Yu X, Zhang B, Wang T, Zhang J, Mu S, Liu C, Zhang N (2016) Two-stage pH-sensitive doxorubicin hydrochloride loaded core–shell nanoparticles with dual drug-loading strategies for the potential anti-tumor treatment. RSC Adv 6:104049–10406610.1039/C6RA19242D ↗
3. Han SS, Li ZY, Zhu JY, Han K, Zeng ZY, Hong W, Li WX, Jia HZ, Liu Y, Zhuo RX, Zhang XZ (2015) Dual-pH sensitive charge-reversal polypeptide micelles for tumor-triggered targeting uptake and nuclear drug delivery. Small 11:2543–255410.1002/smll.201402865 ↗
4. Ding J, Shi F, Xiao C, Lin L, Chen L, He C, Zhuang X, Chen X (2011) One-step preparation of reduction-responsive poly(ethylene glycol)-poly(amino acid)s nanogels as efficient intracellular drug delivery platforms. Polymer Chem 2:2857–286410.1039/c1py00360g ↗
5. Chen J, Ding J, Xu W, Sun T, Xiao H, Zhuang X, Chen X (2017) Receptor and microenvironment dual-recognizable nanogel for targeted chemotherapy of highly metastatic malignancy. Nano Lett 17:4526–453310.1021/acs.nanolett.7b02129 ↗
6. Maeda H (2015) Toward a full understanding of the EPR effect in primary and metastatic tumors as well as issues related to its heterogeneity. Adv Drug Deliv Rev 91:3–610.1016/j.addr.2015.01.002 ↗
7. Li S, Zhang T, Xu W, Ding J, Yin F, Xu J, Sun W, Wang H, Sun M, Cai Z, Hua Y (2018) Sarcoma-targeting peptide-decorated polypeptide nanogel intracellularly delivers shikonin for upregulated osteosarcoma necroptosis and diminished pulmonary metastasis. Theranostics 8:1361–137510.7150/thno.18299 ↗
8. Kanapathipillai M, Brock A, Ingber DE (2014) Nanoparticle targeting of anti-cancer drugs that alter intracellular signaling or influence the tumor microenvironment. Adv Drug Deliv Rev 79–80:107–11810.1016/j.addr.2014.05.005 ↗
9. Feng L, Dong Z, Tao D, Zhang Y, Liu Z (2017) The acidic tumor microenvironment: a target for smart cancer nano-theranostics. Natl Sci Rev 5:269–28610.1093/nsr/nwx062 ↗
10. Dong C, Liu Z, Zhang L, Guo W, Li X, Liu J, Wang H, Chang J (2015) pHe-induced charge-reversible NIR fluorescence nanoprobe for tumor-specific imaging. ACS Appl Mater Interfaces 7:7566–757510.1021/am509011y ↗
11. Du JZ, Du XJ, Mao CQ, Wang J (2011) Tailor-made dual pH-sensitive polymer-doxorubicin nanoparticles for efficient anticancer drug delivery. J Am Chem Soc 133:17560–1756310.1021/ja207150n ↗
12. Sun CY, Shen S, Xu CF, Li HJ, Liu Y, Cao ZT, Yang XZ, Xia JX, Wang J (2015) Tumor acidity-sensitive polymeric vector for active targeted siRNA delivery. J Am Chem Soc 137:15217–1522410.1021/jacs.5b09602 ↗
13. Li J, Yu X, Wang Y, Yuan Y, Xiao H, Cheng D, Shuai X (2014) A reduction and pH dual-sensitive polymeric vector for long-circulating and tumor-targeted siRNA delivery. Adv Mater 26:8217–822410.1002/adma.201403877 ↗
14. Pacardo DB, Ligler FS, Gu Z (2015) Programmable nanomedicine: synergistic and sequential drug delivery systems. Nanoscale 7:3381–339110.1039/C4NR07677J ↗
15. Xing T, Mao C, Lai B, Yan L (2012) Synthesis of disulfide-cross-linked polypeptide nanogel conjugated with a near-infrared fluorescence probe for direct imaging of reduction-induced drug release. ACS Appl Mater Interfaces 4:5662–567210.1021/am301600u ↗
16. Ding J, Shi F, Li D, Chen L, Zhuang X, Chen X (2013) Enhanced endocytosis of acid-sensitive doxorubicin derivatives with intelligent nanogel for improved security and efficacy. Biomater Sci 1:633–64610.1039/C3BM60024F ↗
17. Chen J, Ding J, Wang Y, Cheng J, Ji S, Zhuang X, Chen X (2017) Sequentially responsive shell-stacked nanoparticles for deep penetration into solid tumors. Adv Mater. https://doi.org/10.1002/adma.20170117010.1002/adma.201701170 ↗
18. Guo H, Xu W, Chen J, Yan L, Ding J, Hou Y, Chen X (2017) Positively charged polypeptide nanogel enhances mucoadhesion and penetrability of 10-hydroxycamptothecin in orthotopic bladder carcinoma. J Control Release 259:136–14810.1016/j.jconrel.2016.12.041 ↗
19. Huang K, Shi B, Xu W, Ding J, Yang Y, Liu H, Zhuang X, Chen X (2015) Reduction-responsive polypeptide nanogel delivers antitumor drug for improved efficacy and safety. Acta Biomater 27:179–19310.1016/j.actbio.2015.08.049 ↗
20. Shi F, Ding J, Xiao C, Zhuang X, He C, Chen L, Chen X (2012) Intracellular microenvironment responsive PEGylated polypeptide nanogels with ionizable cores for efficient doxorubicin loading and triggered release. J Mater Chem 22:14168–1417910.1039/c2jm32033a ↗
21. Tang S, Meng Q, Sun H, Su J, Yin Q, Zhang Z, Yu H, Chen L, Gu W, Li Y (2017) Dual pH-sensitive micelles with charge-switch for controlling cellular uptake and drug release to treat metastatic breast cancer. Biomaterials 114:44–5310.1016/j.biomaterials.2016.06.005 ↗
22. Chen F, Zhang J, Wang L, Wang Y, Chen M (2015) Tumor pH(e)-triggered charge-reversal and redox-responsive nanoparticles for docetaxel delivery in hepatocellular carcinoma treatment. Nanoscale 7:15763–1577910.1039/C5NR04612B ↗
23. Li Y, Maciel D, Rodrigues J, Shi X, Tomas H (2015) Biodegradable polymer nanogels for drug/nucleic acid delivery. Chem Rev 115:8564–860810.1021/cr500131f ↗
24. Gravel C, Lapierre D, Labelle J, Keillor JW (2007) Acyl transfer from carboxylate, carbonate, and thiocarbonate esters to enzymatic and nonenzymatic thiolates. Can J Chem 85:164–17410.1139/v07-011 ↗
25. Sulistio A, Widjaya A, Blencowe A, Zhang X, Qiao G (2011) Star polymers composed entirely of amino acid building blocks: a route towards stereospecific, biodegradable and hierarchically functionalized stars. Chem Commun 47:1151–115310.1039/C0CC03541F ↗
26. Jing T, Fu L, Liu L, Yan L (2016) A reduction-responsive polypeptide nanogel encapsulating NIR photosensitizer for imaging guided photodynamic therapy. Polym Chem 7:951–95710.1039/C5PY01629K ↗
27. Kataoka K, Harada A, Nagasaki Y (2001) Block copolymer micelles for drug delivery: design, characterization and biological significance. Adv Drug Deliv Rev 47:113–13110.1016/S0169-409X(00)00124-1 ↗
28. Zhai D, Xu W, Zhang L, Chang YT (2014) The role of “disaggregation” in optical probe development. Chem Soc Rev 43:2402–241110.1039/c3cs60368g ↗
29. Yang F, Teves SS, Kemp CJ, Henikoff S (2014) Doxorubicin, DNA torsion, and chromatin dynamics. Biochim Biophys Acta 1845:84–89
30. Nemoto S, Xiang J, Huang S, Lin A (1998) Induction of apoptosis by SB202190 through inhibition of p38β mitogen-activated protein kinase. J Bio Chem 273:16415–1642010.1074/jbc.273.26.16415 ↗