The Effect of Multistage Nanovector Targeting of VEGFR2 Positive Tumor Endothelia on Cell Adhesion and Local Payload Accumulation

Overview

Journal Biomaterials

Specialty Biomedical Engineering

Date 2014 Sep 2

PMID 25176066

Citations 13

Authors

Jonathan O Martinez

Michael Evangelopoulos

Vivek Karun

Evan Shegog

Joshua A Wang

Christian Boada

Xuewu Liu

Mauro Ferrari

Ennio Tasciotti

Affiliations

Soon will be listed here.

Abstract

Nanovectors are a viable solution to the formulation of poorly soluble anticancer drugs. Their bioaccumulation in the tumor parenchyma is mainly achieved exploiting the enhanced permeability and retention (EPR) effect of the leaky neovasculature. In this paper we demonstrate that multistage nanovectors (MSV) exhibit rapid tumoritropic homing independent of EPR, relying on particle geometry and surface adhesion. By studying endothelial cells overexpressing vascular endothelial growth factor receptor-2 (VEGFR2), we developed MSV able to preferentially target VEGFR2 expressing tumor-associated vessels. Static and dynamic targeting revealed that MSV conjugated with anti-VEGFR2 antibodies displayed greater than a 4-fold increase in targeting efficiency towards VEGFR2 expressing cells while exhibiting minimal adherence to control cells. Additionally, VEGFR2 conjugation bestowed MSV with a significant increase in breast tumor targeting and in the delivery of a model payload while decreasing their accumulation in the liver. Surface functionalization with an anti-VEGFR2 antibody provided enhanced affinity towards the tumor vascular endothelium, which promoted enhanced adhesion and tumoritropic accumulation of a reporter molecule released by the MSV.

Citing Articles

Lysyl oxidase engineered lipid nanovesicles for the treatment of triple negative breast cancer.

De Vita A, Liverani C, Molinaro R, Martinez J, Hartman K, Spadazzi C Sci Rep. 2021; 11(1):5107.

PMID: 33658580 PMC: 7930284. DOI: 10.1038/s41598-021-84492-3.

Development and Characterization of PLGA-Based Multistage Delivery System for Enhanced Payload Delivery to Targeted Vascular Endothelium.

Palma-Chavez J, Fuentes K, Applegate B, Jo J, Charoenphol P Macromol Biosci. 2021; 21(3):e2000377.

PMID: 33393217 PMC: 8203499. DOI: 10.1002/mabi.202000377.

Manipulation of immune‒vascular crosstalk: new strategies towards cancer treatment.

Zhao Y, Yu X, Li J Acta Pharm Sin B. 2020; 10(11):2018-2036.

PMID: 33304777 PMC: 7714955. DOI: 10.1016/j.apsb.2020.09.014.

Cell membrane protein functionalization of nanoparticles as a new tumor-targeting strategy.

Pasto A, Giordano F, Evangelopoulos M, Amadori A, Tasciotti E Clin Transl Med. 2019; 8(1):8.

PMID: 30877412 PMC: 6420595. DOI: 10.1186/s40169-019-0224-y.

Trends towards Biomimicry in Theranostics.

Evangelopoulos M, Parodi A, Martinez J, Tasciotti E Nanomaterials (Basel). 2018; 8(9).

PMID: 30134564 PMC: 6164646. DOI: 10.3390/nano8090637.

References

Raoof M, Cisneros B, Guven A, Phounsavath S, Corr S, Wilson L . Remotely triggered cisplatin release from carbon nanocapsules by radiofrequency fields. Biomaterials. 2012; 34(7):1862-9. PMC: 3694780. DOI: 10.1016/j.biomaterials.2012.11.033. View

Huang H, Held-Feindt J, Buhl R, Mehdorn H, Mentlein R . Expression of VEGF and its receptors in different brain tumors. Neurol Res. 2005; 27(4):371-7. DOI: 10.1179/016164105X39833. View

Martinez J, Brown B, Quattrocchi N, Evangelopoulos M, Ferrari M, Tasciotti E . Multifunctional to multistage delivery systems: The evolution of nanoparticles for biomedical applications. Chin Sci Bull. 2014; 57(31):3961-3971. PMC: 3938208. DOI: 10.1007/s11434-012-5387-5. View

Matsumura Y, Maeda H . A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res. 1986; 46(12 Pt 1):6387-92. View

Azim Jr H, de Azambuja E, Colozza M, Bines J, Piccart M . Long-term toxic effects of adjuvant chemotherapy in breast cancer. Ann Oncol. 2011; 22(9):1939-1947. DOI: 10.1093/annonc/mdq683. View

Parodi A, Quattrocchi N, van de Ven A, Chiappini C, Evangelopoulos M, Martinez J . Synthetic nanoparticles functionalized with biomimetic leukocyte membranes possess cell-like functions. Nat Nanotechnol. 2012; 8(1):61-8. PMC: 3751189. DOI: 10.1038/nnano.2012.212. View

Folkman J . Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971; 285(21):1182-6. DOI: 10.1056/NEJM197111182852108. View

Song E, Zhu P, Lee S, Chowdhury D, Kussman S, Dykxhoorn D . Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors. Nat Biotechnol. 2005; 23(6):709-17. DOI: 10.1038/nbt1101. View

Terman B, Carrion M, Dimitrov D, Armellino D, GOSPODAROWICZ D, Bohlen P . Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor. Biochem Biophys Res Commun. 1992; 187(3):1579-86. DOI: 10.1016/0006-291x(92)90483-2. View

10.

Wu E, Park J, Park J, Segal E, Cunin F, Sailor M . Oxidation-triggered release of fluorescent molecules or drugs from mesoporous Si microparticles. ACS Nano. 2009; 2(11):2401-9. PMC: 2664163. DOI: 10.1021/nn800592q. View

11.

Godin B, Chiappini C, Srinivasan S, Alexander J, Yokoi K, Ferrari M . Discoidal Porous Silicon Particles: Fabrication and Biodistribution in Breast Cancer Bearing Mice. Adv Funct Mater. 2012; 22(20):4225-4235. PMC: 3516182. DOI: 10.1002/adfm.201200869. View

12.

Kim J, Cho J, Seidler P, Kurland N, Yadavalli V . Investigations of chemical modifications of amino-terminated organic films on silicon substrates and controlled protein immobilization. Langmuir. 2010; 26(4):2599-608. DOI: 10.1021/la904027p. View

13.

Hou H, Nieto A, Ma F, Freeman W, Sailor M, Cheng L . Tunable sustained intravitreal drug delivery system for daunorubicin using oxidized porous silicon. J Control Release. 2014; 178:46-54. PMC: 3951847. DOI: 10.1016/j.jconrel.2014.01.003. View

14.

Park M, Choi M, Kwak D, Oh K, Yoon D, Han S . Anti-cancer effect of bee venom in prostate cancer cells through activation of caspase pathway via inactivation of NF-κB. Prostate. 2011; 71(8):801-12. DOI: 10.1002/pros.21296. View

15.

Martinez J, Boada C, Yazdi I, Evangelopoulos M, Brown B, Liu X . Short and long term, in vitro and in vivo correlations of cellular and tissue responses to mesoporous silicon nanovectors. Small. 2012; 9(9-10):1722-33. PMC: 3707147. DOI: 10.1002/smll.201201939. View

16.

Decuzzi P, Ferrari M . Design maps for nanoparticles targeting the diseased microvasculature. Biomaterials. 2007; 29(3):377-84. DOI: 10.1016/j.biomaterials.2007.09.025. View

17.

Tasciotti E, Godin B, Martinez J, Chiappini C, Bhavane R, Liu X . Near-infrared imaging method for the in vivo assessment of the biodistribution of nanoporous silicon particles. Mol Imaging. 2011; 10(1):56-68. PMC: 3088648. View

18.

Lee S, Ferrari M, Decuzzi P . Shaping nano-/micro-particles for enhanced vascular interaction in laminar flows. Nanotechnology. 2009; 20(49):495101. DOI: 10.1088/0957-4484/20/49/495101. View

19.

Potente M, Gerhardt H, Carmeliet P . Basic and therapeutic aspects of angiogenesis. Cell. 2011; 146(6):873-87. DOI: 10.1016/j.cell.2011.08.039. View

20.

Castanotto D, Rossi J . The promises and pitfalls of RNA-interference-based therapeutics. Nature. 2009; 457(7228):426-33. PMC: 2702667. DOI: 10.1038/nature07758. View