Alternating block copolymer-based nanoparticles as tools to modulate the loading of multiple chemotherapeutics and imaging probes

被引:14
作者
Mattu, C. [1 ,6 ]
Brachi, G. [1 ,6 ]
Menichetti, L. [2 ,3 ]
Flori, A. [3 ]
Armanetti, P. [2 ]
Ranzato, E. [4 ]
Martinotti, S. [5 ]
Nizzero, S. [6 ,7 ]
Ferrari, M. [6 ,8 ]
Ciardelli, G. [1 ]
机构
[1] Politecn Torino, DIMEAS, C So Duca Abruzzi 24, I-10129 Turin, Italy
[2] CNR, Inst Clin Physiol, Via G Moruzzi 1, I-56124 Pisa, Italy
[3] Fdn Reg Toscana G Monasterio, Via Giuseppe Moruzzi 1, I-56124 Pisa, Italy
[4] Univ Piemonte Orientale, DiSIT Dipartimento Sci & Innovaz Tecnol, Piazza St Eusebio 5, I-13100 Vercelli, Italy
[5] Univ Piemonte Orientale, DiSIT Dipartimento Sci & Innovaz Tecnol, Viale Teresa Michel 11, I-15121 Alessandria, Italy
[6] Houston Methodist Hosp, Res Inst, Dept Nanomed, Houston, TX 77030 USA
[7] Rice Univ, Smalley Curl Inst, Appl Phys Grad Program, Houston, TX 77005 USA
[8] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA
关键词
IRON-OXIDE NANOPARTICLES; SEMICONDUCTING POLYMER NANOPARTICLES; DRUG-DELIVERY; CONTRAST AGENTS; CANCER-THERAPY; REGENERATIVE MEDICINE; DOCETAXEL; DOXORUBICIN; MICELLES; RELEASE;
D O I
10.1016/j.actbio.2018.09.021
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Cancer therapy often relies on the combined action of different molecules to overcome drug resistance and enhance patient outcome. Combined strategies relying on molecules with different pharmacokinetics often fail due to the lack of concomitant tumor accumulation and, thus, to the loss of synergistic effect. Due to their ability to enhance treatment efficiency, improve drug pharmacokinetics, and reduce adverse effects, polymer nanoparticles (PNPs) have been widely investigated as co-delivery vehicles for cancer therapies. However, co-encapsulation of different drugs and probes in PNPs requires a flexible polymer platform and a tailored particle design, in which both the bulk and surface properties of the carriers are carefully controlled. In this work, we propose a core-shell PNP design based on a polyurethane (PUR) core and a phospholipid external surface. The modulation of the hydrophilic/hydrophobic balance of the PUR core enhanced the encapsulation of two chemotherapeutics with dramatically different water solubility (Doxorubicin hydrochloride, DOXO and Docetaxel, DCTXL) and of Iron Oxide Nanoparticles for MRI imaging. The outer shell remained unchanged among the platforms, resulting in un-modified cellular uptake and in vivo biodistribution. We demonstrate that the choice of PUR core allowed a high entrapment efficiency of all drugs, superior or comparable to previously reported results, and that higher core hydrophilicity enhances the loading efficiency of the hydrophilic DOXO and the MRI contrast effect. Moreover, we show that changing the PUR core did not alter the surface properties of the carriers, since all particles showed a similar behavior in terms of cell internalization and in vivo biodistribution. We also show that PUR PNPs have high passive tumor accumulation and that they can efficient co-deliver the two drugs to the tumor, reaching an 11-fold higher DOXO/DCTXL ratio in tumor as compared to free drugs. (C) 2018 Acta Materialia Inc. Published by Elsevier Ltd.
引用
收藏
页码:341 / 351
页数:11
相关论文
共 42 条
[1]   HPLC quantification of doxorubicin in plasma and tissues of rats treated with doxorubicin loaded poly(alkylcyanoacrylate) nanoparticles [J].
Alhareth, Khairallah ;
Vauthier, Christine ;
Gueutin, Claire ;
Ponchel, Gilles ;
Moussa, Fathi .
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 2012, 887 :128-132
[2]   Strategies for non-invasive imaging of polymeric biomaterial in vascular tissue engineering and regenerative medicine using ultrasound and photoacoustic techniques [J].
Avigo, Cinzia ;
Flori, Alessandra ;
Armanetti, Paolo ;
Di Lascio, Nicole ;
Kusmic, Claudia ;
Jose, Jithin ;
Losi, Paola ;
Soldani, Giorgio ;
Faita, Francesco ;
Menichetti, Luca .
POLYMER INTERNATIONAL, 2016, 65 (07) :734-740
[3]   Principles of nanoparticle design for overcoming biological barriers to drug delivery [J].
Blanco, Elvin ;
Shen, Haifa ;
Ferrari, Mauro .
NATURE BIOTECHNOLOGY, 2015, 33 (09) :941-951
[4]  
Blanco E, 2014, THER DELIV, V5, P737, DOI [10.4155/TDE.14.51, 10.4155/tde.14.51]
[5]   Colocalized Delivery of Rapamycin and Paclitaxel to Tumors Enhances Synergistic Targeting of the PI3K/Akt/mTOR Pathway [J].
Blanco, Elvin ;
Sangai, Takafumi ;
Wu, Suhong ;
Hsiao, Angela ;
Ruiz-Esparza, Guillermo U. ;
Gonzalez-Delgado, Carlos A. ;
Cara, Francisca E. ;
Granados-Principal, Sergio ;
Evans, Kurt W. ;
Akcakanat, Argun ;
Wang, Ying ;
Do, Kim-Anh ;
Meric-Bernstam, Funda ;
Ferrari, Mauro .
MOLECULAR THERAPY, 2014, 22 (07) :1310-1319
[6]   Passion fruit-like nano-architectures: a general synthesis route [J].
Cassano, D. ;
David, J. ;
Luin, S. ;
Voliani, V. .
SCIENTIFIC REPORTS, 2017, 7
[7]   Design of water-based ferrofluids as contrast agents for magnetic resonance imaging [J].
Casula, Maria F. ;
Corrias, Anna ;
Arosio, Paolo ;
Lascialfari, Alessandro ;
Sen, Tapas ;
Floris, Patrizia ;
Bruce, Ian J. .
JOURNAL OF COLLOID AND INTERFACE SCIENCE, 2011, 357 (01) :50-55
[8]   Emerging Role of the Spleen in the Pharmacokinetics of Monoclonal Antibodies, Nanoparticles and Exosomes [J].
Cataldi, Mauro ;
Vigliotti, Chiara ;
Mosca, Teresa ;
Cammarota, MariaRosaria ;
Capone, Domenico .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2017, 18 (06)
[9]  
Dash S, 2010, ACTA POL PHARM, V67, P217
[10]  
Dessy A. P. A., 2012, NANO BIOMED ENG, V4, P6