Intracellularly Swollen Polypeptide Nanogel Assists Hepatoma Chemotherapy

Overview

Journal Theranostics

Date 2017 Mar 4

PMID 28255361

Citations 15

Authors

Bo Shi

Kexin Huang

Jianxun Ding

Weiguo Xu

Yu Yang

Haiyan Liu

Lesan Yan

Xuesi Chen

Affiliations

Soon will be listed here.

Abstract

Nowadays, chemotherapy is one of the principal modes of treatment for tumor patients. However, the traditional formulations of small molecule drugs show short circulation time, low tumor selectivity, and high toxicity to normal tissues. To address these problems, a facilely prepared, and pH and reduction dual-responsive polypeptide nanogel was prepared for selectively intracellular delivery of chemotherapy drug. As a model drug, doxorubicin (DOX) was loaded into the nanogel through a sequential dispersion and dialysis technique, resulting in a high drug loading efficiency (DLE) of 96.7 wt.%. The loading nanogel, defined as NG/DOX, exhibited a uniform spherical morphology with a mean hydrodynamic radius of 58.8 nm, pH and reduction dual-triggered DOX release, efficient cell uptake, and cell proliferation inhibition . Moreover, NG/DOX exhibited improved antitumor efficacy toward H22 hepatoma-bearing BALB/c mouse model compared with free DOX·HCl. Histopathological and immunohistochemical analyses were implemented to further confirm the tumor suppression activity of NG/DOX. Furthermore, the variations of body weight, histopathological morphology, bone marrow cell micronucleus rate, and white blood cell count verified that NG/DOX showed excellent safety . With these excellent properties and , the pH and reduction dual-responsive polypeptide nanogel exhibits great potential for on-demand intracellular delivery of antitumor drug, and holds good prospect for future clinical application.

Citing Articles

The effects of metformin and PCL-sorafenib nanoparticle co-treatment on MCF-7 cell culture model of breast cancer.

Heydarnia E, Sepasi A, Asefi N, Khakshournia S, Mohammadnejad J Naunyn Schmiedebergs Arch Pharmacol. 2024; 397(9):7213-7221.

PMID: 38656346 DOI: 10.1007/s00210-024-03049-z.

Polypeptide-Based Systems: From Synthesis to Application in Drug Delivery.

Stepanova M, Nikiforov A, Tennikova T, Korzhikova-Vlakh E Pharmaceutics. 2023; 15(11).

PMID: 38004619 PMC: 10674432. DOI: 10.3390/pharmaceutics15112641.

Nanogels as Novel Nanocarrier Systems for Efficient Delivery of CNS Therapeutics.

Zhang Y, Zou Z, Liu S, Miao S, Liu H Front Bioeng Biotechnol. 2022; 10:954470.

PMID: 35928954 PMC: 9343834. DOI: 10.3389/fbioe.2022.954470.

Tumor Microenvironment-Responsive Polypeptide Nanogels for Controlled Antitumor Drug Delivery.

Liu Y, Chen L, Shi Q, Zhao Q, Ma H Front Pharmacol. 2021; 12:748102.

PMID: 34776965 PMC: 8578677. DOI: 10.3389/fphar.2021.748102.

A light-controlled multi-step drug release nanosystem targeting tumor hypoxia for synergistic cancer therapy.

Zhang B, Xu Z, Zhou W, Liu Z, Zhao J, Gou S Chem Sci. 2021; 12(35):11810-11820.

PMID: 34659720 PMC: 8442699. DOI: 10.1039/d1sc01888d.

References

Li D, Sun H, Ding J, Tang Z, Zhang Y, Xu W . Polymeric topology and composition constrained polyether-polyester micelles for directional antitumor drug delivery. Acta Biomater. 2013; 9(11):8875-84. DOI: 10.1016/j.actbio.2013.06.041. View

Nukolova N, Oberoi H, Zhao Y, Chekhonin V, Kabanov A, Bronich T . LHRH-targeted nanogels as a delivery system for cisplatin to ovarian cancer. Mol Pharm. 2013; 10(10):3913-21. PMC: 3809768. DOI: 10.1021/mp4003688. View

Ding J, Shi F, Li D, Chen L, Zhuang X, Chen X . Enhanced endocytosis of acid-sensitive doxorubicin derivatives with intelligent nanogel for improved security and efficacy. Biomater Sci. 2020; 1(6):633-646. DOI: 10.1039/c3bm60024f. View

Wolfe T, Chatterjee D, Lee J, Grant J, Bhattarai S, Tailor R . Targeted gold nanoparticles enhance sensitization of prostate tumors to megavoltage radiation therapy in vivo. Nanomedicine. 2015; 11(5):1277-83. PMC: 4476911. DOI: 10.1016/j.nano.2014.12.016. View

Roth B, Krilov L, Adams S, Aghajanian C, Bach P, Braiteh F . Clinical cancer advances 2012: annual report on progress against cancer from the american society of clinical oncology. J Clin Oncol. 2012; 31(1):131-61. DOI: 10.1200/JCO.2012.47.1938. View

Soragni A, Janzen D, Johnson L, Lindgren A, Nguyen A, Tiourin E . A Designed Inhibitor of p53 Aggregation Rescues p53 Tumor Suppression in Ovarian Carcinomas. Cancer Cell. 2016; 29(1):90-103. PMC: 4733364. DOI: 10.1016/j.ccell.2015.12.002. View

Li H, Du J, Du X, Xu C, Sun C, Wang H . Stimuli-responsive clustered nanoparticles for improved tumor penetration and therapeutic efficacy. Proc Natl Acad Sci U S A. 2016; 113(15):4164-9. PMC: 4839420. DOI: 10.1073/pnas.1522080113. View

Ueki N, Wang W, Swenson C, McNaughton C, Sampson N, Hayman M . Synthesis and Preclinical Evaluation of a Highly Improved Anticancer Prodrug Activated by Histone Deacetylases and Cathepsin L. Theranostics. 2016; 6(6):808-16. PMC: 4860889. DOI: 10.7150/thno.13826. View

Xu W, Ding J, Xiao C, Li L, Zhuang X, Chen X . Versatile preparation of intracellular-acidity-sensitive oxime-linked polysaccharide-doxorubicin conjugate for malignancy therapeutic. Biomaterials. 2015; 54:72-86. DOI: 10.1016/j.biomaterials.2015.03.021. View

10.

Parks S, Chiche J, Pouyssegur J . Disrupting proton dynamics and energy metabolism for cancer therapy. Nat Rev Cancer. 2013; 13(9):611-23. DOI: 10.1038/nrc3579. View

11.

Ding J, Xu W, Zhang Y, Sun D, Xiao C, Liu D . Self-reinforced endocytoses of smart polypeptide nanogels for "on-demand" drug delivery. J Control Release. 2013; 172(2):444-55. DOI: 10.1016/j.jconrel.2013.05.029. View

12.

Adiseshaiah P, Hall J, McNeil S . Nanomaterial standards for efficacy and toxicity assessment. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2010; 2(1):99-112. DOI: 10.1002/wnan.66. View

13.

Zhang R, Cai P, Zhang T, Chen K, Li J, Cheng J . Polymer-lipid hybrid nanoparticles synchronize pharmacokinetics of co-encapsulated doxorubicin-mitomycin C and enable their spatiotemporal co-delivery and local bioavailability in breast tumor. Nanomedicine. 2016; 12(5):1279-90. DOI: 10.1016/j.nano.2015.12.383. View

14.

Cheng P, Rao X, Duan X, Li X, Egger M, McMasters K . Virotherapy targeting cyclin E overexpression in tumors with adenovirus-enhanced cancer-selective promoter. J Mol Med (Berl). 2014; 93(2):211-23. PMC: 4320008. DOI: 10.1007/s00109-014-1214-6. View

15.

Huang K, Shi B, Xu W, Ding J, Yang Y, Liu H . Reduction-responsive polypeptide nanogel delivers antitumor drug for improved efficacy and safety. Acta Biomater. 2015; 27:179-193. DOI: 10.1016/j.actbio.2015.08.049. View

16.

Xu W, Ding J, Li L, Xiao C, Zhuang X, Chen X . Acid-labile boronate-bridged dextran-bortezomib conjugate with up-regulated hypoxic tumor suppression. Chem Commun (Camb). 2015; 51(31):6812-5. DOI: 10.1039/c5cc01371b. View

17.

Maciel D, Figueira P, Xiao S, Hu D, Shi X, Rodrigues J . Redox-responsive alginate nanogels with enhanced anticancer cytotoxicity. Biomacromolecules. 2013; 14(9):3140-6. DOI: 10.1021/bm400768m. View

18.

Ge Z, Liu S . Functional block copolymer assemblies responsive to tumor and intracellular microenvironments for site-specific drug delivery and enhanced imaging performance. Chem Soc Rev. 2013; 42(17):7289-325. DOI: 10.1039/c3cs60048c. View

19.

Li M, Tang Z, Lv S, Song W, Hong H, Jing X . Cisplatin crosslinked pH-sensitive nanoparticles for efficient delivery of doxorubicin. Biomaterials. 2014; 35(12):3851-64. DOI: 10.1016/j.biomaterials.2014.01.018. View

20.

Ding J, Xiao C, Yan L, Tang Z, Zhuang X, Chen X . pH and dual redox responsive nanogel based on poly(l-glutamic acid) as potential intracellular drug carrier. J Control Release. 2011; 152 Suppl 1:e11-3. DOI: 10.1016/j.jconrel.2011.08.091. View