Skip to main content
Top
Published in: Investigational New Drugs 1/2024

21-12-2023 | Research

Targeted delivery of liposomal Ribociclib to SLC7A5 transporters in breast cancer cells

Authors: Mahtab Afsharzadeh, Jaleh Varshosaz, Mina Mirian, Farshid Hasanzadeh

Published in: Investigational New Drugs | Issue 1/2024

Login to get access

Summary

This study aimed to prepare SLC7A5 transporters targeted liposomes of Ribociclib (RB) by stear(o)yl conjugation of Phe, Asp, Glu amino acids to liposomes as targeting moieties. The liposomes were optimized for their formulations. Cell analysis on two cell lines of MCF-7 and NIH-3T3 were done including; cell viability test by MTT assay, cellular uptake, and cell cycle arrest by flow cytometry. The optimal liposomes showed the particle size of 123.6 ± 1.3 nm, drug loading efficiency and release efficiency of 83.87% ± 1.33% and 60.55% ± 0.46%, respectively. The RB loaded liposomes showed no hemolysis activity. Targeted liposomes increased cytotoxicity on MCF-7 cells more significantly than NIH-3T3 cells. Cell flow cytometry indicated that targeted liposomes uptake was superior to plain (non-targted) liposomes and free drug. Free drug and RB-loaded liposomes interrupted cell cycle in G1. However, amino acid-targeted liposomes arrested cells more than the free drug at this stage. Targeted liposomes reduced cell cycle with more interruption in the G2/M phase compared to the negative control.

Graphical abstract

Literature
1.
go back to reference Lima SM et al (2021) Global breast cancer incidence and mortality trends by region, age-groups, and fertility patterns. EClinMedicine 38:100985CrossRef Lima SM et al (2021) Global breast cancer incidence and mortality trends by region, age-groups, and fertility patterns. EClinMedicine 38:100985CrossRef
2.
3.
4.
go back to reference Tosello G et al (2018) Breast surgery for metastatic breast cancer. Cochrane Database System Rev 3:CD011276 Tosello G et al (2018) Breast surgery for metastatic breast cancer. Cochrane Database System Rev 3:CD011276
5.
go back to reference Slamon DJ et al (2020) Overall survival with Ribociclib plus fulvestrant in advanced breast cancer. New Eng J Med 382(6):514–524CrossRefPubMed Slamon DJ et al (2020) Overall survival with Ribociclib plus fulvestrant in advanced breast cancer. New Eng J Med 382(6):514–524CrossRefPubMed
6.
go back to reference Shah A et al (2018) FDA approval: Ribociclib for the treatment of postmenopausal women with hormone receptor-positive, HER2-negative advanced or metastatic breast cancer. Clin Cancer Res 24(13):2999–3004CrossRefPubMed Shah A et al (2018) FDA approval: Ribociclib for the treatment of postmenopausal women with hormone receptor-positive, HER2-negative advanced or metastatic breast cancer. Clin Cancer Res 24(13):2999–3004CrossRefPubMed
7.
go back to reference Arora S et al (2017) Project ECHO: an effective means of increasing palliative care capacity. Am J Manag Care 23(7):SP267–SP271 Arora S et al (2017) Project ECHO: an effective means of increasing palliative care capacity. Am J Manag Care 23(7):SP267–SP271
9.
go back to reference Hurler J et al (2013) The effect of lipid composition and liposome size on the release properties of liposomes-in-hydrogel. Int J Pharm 456(1):49–57CrossRefPubMed Hurler J et al (2013) The effect of lipid composition and liposome size on the release properties of liposomes-in-hydrogel. Int J Pharm 456(1):49–57CrossRefPubMed
10.
go back to reference Guimarães D et al (2021) Design of liposomes as drug delivery system for therapeutic applications. Int J Pharm 601:120571CrossRefPubMed Guimarães D et al (2021) Design of liposomes as drug delivery system for therapeutic applications. Int J Pharm 601:120571CrossRefPubMed
11.
go back to reference Yin Y et al (2022) Choline-induced SLC5A7 impairs colorectal cancer growth by stabilizing p53 protein. Cancer Let 525:55–66CrossRef Yin Y et al (2022) Choline-induced SLC5A7 impairs colorectal cancer growth by stabilizing p53 protein. Cancer Let 525:55–66CrossRef
12.
go back to reference Gynther M et al (2010) Brain uptake of ketoprofen-lysine prodrug in rats. Int J Pharm 399(1–2):121–128CrossRefPubMed Gynther M et al (2010) Brain uptake of ketoprofen-lysine prodrug in rats. Int J Pharm 399(1–2):121–128CrossRefPubMed
13.
go back to reference Wu W et al (2015) Aspartate-modified doxorubicin on its N-terminal increases drug accumulation in LAT1-overexpressing tumors. Cancer Sci 106(6):747–756CrossRefPubMedPubMedCentral Wu W et al (2015) Aspartate-modified doxorubicin on its N-terminal increases drug accumulation in LAT1-overexpressing tumors. Cancer Sci 106(6):747–756CrossRefPubMedPubMedCentral
14.
go back to reference Shennan DB et al (2004) L-Leucine transport in human breast cancer cells (MCF-7 and MDA-MB-231): Kinetics, regulation by estrogen and molecular identity of the transporter. Biochim et Biophy Acta - Biomembranes 1664(2):206–216CrossRef Shennan DB et al (2004) L-Leucine transport in human breast cancer cells (MCF-7 and MDA-MB-231): Kinetics, regulation by estrogen and molecular identity of the transporter. Biochim et Biophy Acta - Biomembranes 1664(2):206–216CrossRef
15.
go back to reference Metselaar JM et al (2003) A novel family of l-amino acid-based biodegradable polymer-lipid conjugates for the development of long-circulating liposomes with effective drug-targeting capacity. Bioconjug Chem 14(6):1156–1164CrossRefPubMed Metselaar JM et al (2003) A novel family of l-amino acid-based biodegradable polymer-lipid conjugates for the development of long-circulating liposomes with effective drug-targeting capacity. Bioconjug Chem 14(6):1156–1164CrossRefPubMed
16.
go back to reference Li L et al (2016) Large amino acid transporter 1 mediated glutamate modified docetaxel-loaded liposomes for glioma targeting. Colloid Surf B: Biointerf 141:260–267CrossRef Li L et al (2016) Large amino acid transporter 1 mediated glutamate modified docetaxel-loaded liposomes for glioma targeting. Colloid Surf B: Biointerf 141:260–267CrossRef
17.
go back to reference Li L et al (2017) Targeting tumor highly-expressed LAT1 transporter with amino acid-modified nanoparticles: Toward a novel active targeting strategy in breast cancer therapy. Nanomed Nanotech Biol Med 13(3):987–998ADSCrossRef Li L et al (2017) Targeting tumor highly-expressed LAT1 transporter with amino acid-modified nanoparticles: Toward a novel active targeting strategy in breast cancer therapy. Nanomed Nanotech Biol Med 13(3):987–998ADSCrossRef
18.
go back to reference Wang Z et al (2019) Tyrosine modified irinotecan-loaded liposomes capable of simultaneously targeting LAT1 and ATB0,+ for efficient tumor therapy. J Control Rel 316:22–33CrossRef Wang Z et al (2019) Tyrosine modified irinotecan-loaded liposomes capable of simultaneously targeting LAT1 and ATB0,+ for efficient tumor therapy. J Control Rel 316:22–33CrossRef
19.
go back to reference Brandl M (2001) Liposomes as drug carriers: A technological approach. Biotechnol Annu Rev 7:59–85CrossRefPubMed Brandl M (2001) Liposomes as drug carriers: A technological approach. Biotechnol Annu Rev 7:59–85CrossRefPubMed
20.
go back to reference Pinto F et al (2018) Design of multifunctional nanostructured lipid carriers enriched with α-tocopherol using vegetable oils. Ind Crops Product 118:149–159CrossRef Pinto F et al (2018) Design of multifunctional nanostructured lipid carriers enriched with α-tocopherol using vegetable oils. Ind Crops Product 118:149–159CrossRef
21.
go back to reference Kępczyński M et al (2008) Which physical and structural factors of liposome carriers control their drug-entrapment efficiency. Chem Phys Lipid 155(1):7–15 Kępczyński M et al (2008) Which physical and structural factors of liposome carriers control their drug-entrapment efficiency. Chem Phys Lipid 155(1):7–15
22.
go back to reference Zhao L et al (2015) Preparation of liposomes using supercritical carbon dioxide technology: Effects of phospholipids and sterols. Food Res Int 77:63–72CrossRef Zhao L et al (2015) Preparation of liposomes using supercritical carbon dioxide technology: Effects of phospholipids and sterols. Food Res Int 77:63–72CrossRef
24.
go back to reference Accardo A, Morelli G (2015) Peptide-targeted liposomes for selective drug delivery: advantages and problematic issues. Biopolymers 104(5):462–479CrossRefPubMed Accardo A, Morelli G (2015) Peptide-targeted liposomes for selective drug delivery: advantages and problematic issues. Biopolymers 104(5):462–479CrossRefPubMed
25.
go back to reference Hong SS et al (2015) Effects of triglycerides on the hydrophobic drug loading capacity of saturated phosphatidylcholine-based liposomes. Int J Pharm 483(1–2):142–150CrossRefPubMed Hong SS et al (2015) Effects of triglycerides on the hydrophobic drug loading capacity of saturated phosphatidylcholine-based liposomes. Int J Pharm 483(1–2):142–150CrossRefPubMed
26.
go back to reference Kaddah S et al (2018) Cholesterol modulates the liposome membrane fluidity and permeability for a hydrophilic molecule. Food Chem Toxicol 113:40–48CrossRefPubMed Kaddah S et al (2018) Cholesterol modulates the liposome membrane fluidity and permeability for a hydrophilic molecule. Food Chem Toxicol 113:40–48CrossRefPubMed
27.
go back to reference Luo Q et al (2016) Transporter occluded-state conformation-induced endocytosis: Amino acid transporter ATB°+-mediated tumor targeting of liposomes for docetaxel delivery for hepatocarcinoma therapy. J Control Rel 243:370–380CrossRef Luo Q et al (2016) Transporter occluded-state conformation-induced endocytosis: Amino acid transporter ATB°+-mediated tumor targeting of liposomes for docetaxel delivery for hepatocarcinoma therapy. J Control Rel 243:370–380CrossRef
28.
go back to reference Kim CK, Park DK (1987) Stability and drug release properties of liposomes containing cytarabine as a drug carrier. Arch Pharm Res 10(2):75–79CrossRef Kim CK, Park DK (1987) Stability and drug release properties of liposomes containing cytarabine as a drug carrier. Arch Pharm Res 10(2):75–79CrossRef
29.
go back to reference Papageorgiou F et al (2019) Physicochemical study of the protein–liposome interactions: influence of liposome composition and concentration on protein binding. J Liposome Res 29(4):313–321CrossRef Papageorgiou F et al (2019) Physicochemical study of the protein–liposome interactions: influence of liposome composition and concentration on protein binding. J Liposome Res 29(4):313–321CrossRef
30.
go back to reference Arnida et al (2011) Geometry and surface characteristics of gold nanoparticles influence their biodistribution and uptake by macrophages. Eur J Pharm Biopharm 77(3):417–423CrossRefPubMed Arnida et al (2011) Geometry and surface characteristics of gold nanoparticles influence their biodistribution and uptake by macrophages. Eur J Pharm Biopharm 77(3):417–423CrossRefPubMed
31.
go back to reference Sartaj A et al (2022) Ribociclib nanostructured lipid carrier aimed for breast cancer: formulation optimization, attenuating in vitro specification, and in vivo scrutinization. BioMed Res Int 2022:6009309CrossRefPubMedPubMedCentral Sartaj A et al (2022) Ribociclib nanostructured lipid carrier aimed for breast cancer: formulation optimization, attenuating in vitro specification, and in vivo scrutinization. BioMed Res Int 2022:6009309CrossRefPubMedPubMedCentral
32.
go back to reference Nakanishi T et al (2011) Solute carrier transporters as targets for drug delivery and pharmacological intervention for chemotherapy. J Pharm Sci 100(9):3731–3750CrossRefPubMed Nakanishi T et al (2011) Solute carrier transporters as targets for drug delivery and pharmacological intervention for chemotherapy. J Pharm Sci 100(9):3731–3750CrossRefPubMed
33.
go back to reference Salatin S et al (2015) Effect of the surface modification, size, and shape on cellular uptake of nanoparticles. Cell Biol Int 39(8):881–890CrossRefPubMed Salatin S et al (2015) Effect of the surface modification, size, and shape on cellular uptake of nanoparticles. Cell Biol Int 39(8):881–890CrossRefPubMed
34.
go back to reference Dickson MA (2014) Molecular pathways: CDK4 inhibitors for cancer therapy. Clin Cancer Res 20(13):3379–3383CrossRefPubMed Dickson MA (2014) Molecular pathways: CDK4 inhibitors for cancer therapy. Clin Cancer Res 20(13):3379–3383CrossRefPubMed
35.
go back to reference Kommineni N et al (2022) Stealth liposomal chemotherapeutic agent for triple negative breast cancer with improved pharmacokinetics. Nanotheranostics 6(4):424–435CrossRefPubMedPubMedCentral Kommineni N et al (2022) Stealth liposomal chemotherapeutic agent for triple negative breast cancer with improved pharmacokinetics. Nanotheranostics 6(4):424–435CrossRefPubMedPubMedCentral
36.
Metadata
Title
Targeted delivery of liposomal Ribociclib to SLC7A5 transporters in breast cancer cells
Authors
Mahtab Afsharzadeh
Jaleh Varshosaz
Mina Mirian
Farshid Hasanzadeh
Publication date
21-12-2023
Publisher
Springer US
Published in
Investigational New Drugs / Issue 1/2024
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI
https://doi.org/10.1007/s10637-023-01409-9

Other articles of this Issue 1/2024

Investigational New Drugs 1/2024 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine