Hydrolysable Core Crosslinked Particle for Receptor-mediated PH-sensitive Anticancer Drug Delivery

Overview

Journal New J Chem

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2016 May 3

PMID 27134519

Citations 6

Authors

Xifeng Liu

A Lee Miller 2nd

Brian E Waletzki

Tewodros K Mamo

Michael J Yaszemski

Lichun Lu

Affiliations

Soon will be listed here.

Abstract

Biodegradable micelle systems with both extracellular stabilities and specific targeting properties are highly desirable for anti-cancer drug delivery. Here, we report a biodegradable and crosslinkable poly(propylene fumarate)--poly(lactide--glycolide)--poly(ethylene glycol) (PPF-PLGA-PEG) copolymer conjugated with folate (FA) molecules for receptor-mediated delivery of doxorubicin. Micelles with folate ligands on surface and fumarate bonds within the core were self-assembled and crosslinked, which exhibited better stability against potential physiological conditions during and after drug administration. A pH sensitive drug release profile was observed showing robust release at acidic environment due to the ester hydrolysis of PLGA (50:50). Further, micelles with folate ligands on surface showed strong targeting ability and therapeutic efficacy through receptor-mediated endocytosis, as evidenced by efficacious cancer killing and fatal DNA damage. These results imply promising potential for ligand-conjugated core crosslinked PPF-PLGA-PEG-FA micelles as carrier system for targeted anti-cancer drug delivery.

Citing Articles

Mechanistic Study on the Degradation of Hydrolysable Core-Crosslinked Polymeric Micelles.

Hebels E, van Steenbergen M, Haegebaert R, Seinen C, Mesquita B, van den Dikkenberg A Langmuir. 2023; 39(34):12132-12143.

PMID: 37581242 PMC: 10469444. DOI: 10.1021/acs.langmuir.3c01399.

Rapid conjugation of nanoparticles, proteins and siRNAs to microbubbles by strain-promoted click chemistry for ultrasound imaging and drug delivery.

Liu X, Gong P, Song P, Xie F, Lee Miller 2nd A, Chen S Polym Chem. 2022; 10(6):705-717.

PMID: 36187167 PMC: 9523532. DOI: 10.1039/c8py01721b.

Covalent crosslinking of graphene oxide and carbon nanotube into hydrogels enhances nerve cell responses.

Liu X, Miller Ii A, Park S, Waletzki B, Terzic A, Yaszemski M J Mater Chem B. 2020; 4(43):6930-6941.

PMID: 32263560 PMC: 8844883. DOI: 10.1039/c6tb01722c.

Progress in Polymeric Nano-Medicines for Theranostic Cancer Treatment.

Ali I, Alsehli M, Scotti L, Scotti M, Tsai S, Yu R Polymers (Basel). 2020; 12(3).

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PLGA Microspheres Loaded with β-Cyclodextrin Complexes of Epigallocatechin-3-Gallate for the Anti-Inflammatory Properties in Activated Microglial Cells.

Cheng C, Pho Q, Wu X, Chin T, Chen C, Fang P Polymers (Basel). 2019; 10(5).

PMID: 30966553 PMC: 6415370. DOI: 10.3390/polym10050519.

References

Yhee J, Lee S, Kim K . Advances in targeting strategies for nanoparticles in cancer imaging and therapy. Nanoscale. 2014; 6(22):13383-90. DOI: 10.1039/c4nr04334k. View

Busseron E, Ruff Y, Moulin E, Giuseppone N . Supramolecular self-assemblies as functional nanomaterials. Nanoscale. 2013; 5(16):7098-140. DOI: 10.1039/c3nr02176a. View

Qi R, Liu S, Chen J, Xiao H, Yan L, Huang Y . Biodegradable copolymers with identical cationic segments and their performance in siRNA delivery. J Control Release. 2012; 159(2):251-60. DOI: 10.1016/j.jconrel.2012.01.015. View

Wang S, Lu L, Yaszemski M . Bone-tissue-engineering material poly(propylene fumarate): correlation between molecular weight, chain dimensions, and physical properties. Biomacromolecules. 2006; 7(6):1976-82. PMC: 2530912. DOI: 10.1021/bm060096a. View

Zolnik B, Burgess D . Effect of acidic pH on PLGA microsphere degradation and release. J Control Release. 2007; 122(3):338-44. DOI: 10.1016/j.jconrel.2007.05.034. View

Qi R, Xiao H, Wu S, Li Y, Zhang Y, Jing X . Design and delivery of camplatin to overcome cisplatin drug resistance. J Mater Chem B. 2020; 3(2):176-179. DOI: 10.1039/c4tb01146e. View

Lu Y, Low P . Folate-mediated delivery of macromolecular anticancer therapeutic agents. Adv Drug Deliv Rev. 2002; 54(5):675-93. DOI: 10.1016/s0169-409x(02)00042-x. View

Xiao H, Song H, Yang Q, Cai H, Qi R, Yan L . A prodrug strategy to deliver cisplatin(IV) and paclitaxel in nanomicelles to improve efficacy and tolerance. Biomaterials. 2012; 33(27):6507-19. DOI: 10.1016/j.biomaterials.2012.05.049. View

Wen Y, Collier J . Supramolecular peptide vaccines: tuning adaptive immunity. Curr Opin Immunol. 2015; 35:73-9. PMC: 4610357. DOI: 10.1016/j.coi.2015.06.007. View

10.

Peer D, Karp J, Hong S, Farokhzad O, Margalit R, Langer R . Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol. 2008; 2(12):751-60. DOI: 10.1038/nnano.2007.387. View

11.

Farokhzad O, Cheng J, Teply B, Sherifi I, Jon S, Kantoff P . Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo. Proc Natl Acad Sci U S A. 2006; 103(16):6315-20. PMC: 1458875. DOI: 10.1073/pnas.0601755103. View

12.

Savic R, Azzam T, Eisenberg A, Maysinger D . Assessment of the integrity of poly(caprolactone)-b-poly(ethylene oxide) micelles under biological conditions: a fluorogenic-based approach. Langmuir. 2006; 22(8):3570-8. DOI: 10.1021/la0531998. View

13.

Danhier F, Ansorena E, Silva J, Coco R, Le Breton A, Preat V . PLGA-based nanoparticles: an overview of biomedical applications. J Control Release. 2012; 161(2):505-22. DOI: 10.1016/j.jconrel.2012.01.043. View

14.

Hovorka O, Stastny M, Etrych T, Subr V, Strohalm J, Ulbrich K . Differences in the intracellular fate of free and polymer-bound doxorubicin. J Control Release. 2002; 80(1-3):101-17. DOI: 10.1016/s0168-3659(02)00016-0. View

15.

Rijcken C, Snel C, Schiffelers R, van Nostrum C, Hennink W . Hydrolysable core-crosslinked thermosensitive polymeric micelles: synthesis, characterisation and in vivo studies. Biomaterials. 2007; 28(36):5581-93. DOI: 10.1016/j.biomaterials.2007.08.047. View

16.

Ross J, Chaudhuri P, Ratnam M . Differential regulation of folate receptor isoforms in normal and malignant tissues in vivo and in established cell lines. Physiologic and clinical implications. Cancer. 1994; 73(9):2432-43. DOI: 10.1002/1097-0142(19940501)73:9<2432::aid-cncr2820730929>3.0.co;2-s. View

17.

Wen Y, Liu W, Bagia C, Zhang S, Bai M, Janjic J . Antibody-functionalized peptidic membranes for neutralization of allogeneic skin antigen-presenting cells. Acta Biomater. 2014; 10(11):4759-4767. PMC: 4186902. DOI: 10.1016/j.actbio.2014.08.003. View

18.

Henry M, Cai L, Liu X, Zhang L, Dong J, Chen L . Roles of hydroxyapatite allocation and microgroove dimension in promoting preosteoblastic cell functions on photocured polymer nanocomposites through nuclear distribution and alignment. Langmuir. 2015; 31(9):2851-60. DOI: 10.1021/la504994e. View

19.

Unger F, Wittmar M, Morell F, Kissel T . Branched polyesters based on poly[vinyl-3-(dialkylamino)alkylcarbamate-co-vinyl acetate-co-vinyl alcohol]-graft-poly(D,L-lactide-co-glycolide): effects of polymer structure on in vitro degradation behaviour. Biomaterials. 2008; 29(13):2007-14. DOI: 10.1016/j.biomaterials.2007.12.027. View

20.

Liu X, Lee Miller 2nd A, Waletzki B, Yaszemski M, Lu L . Novel biodegradable poly(propylene fumarate)--poly(l-lactic acid) porous scaffolds fabricated by phase separation for tissue engineering applications. RSC Adv. 2016; 5(27):21301-21309. PMC: 4792309. DOI: 10.1039/C5RA00508F. View