Advances in Clinical and Experimental Medicine
2019, vol. 28, nr 4, April, p. 479–487
Publication type: original article
Low-density lipoprotein-decorated and Adriamycin-loaded silica nanoparticles for tumor-targeted chemotherapy of colorectal cancer
1 Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, China
Background. Chemotherapy for colorectal cancer remains an unsatisfactory method of treatment and requires the development of more advanced drug delivery systems (DDSs). Among inorganic materials, silica nanoparticles (SLNs) have been considered a suitable candidate to be developed as versatile carriers for drug delivery and imaging applications. Low-density lipoprotein (LDL) is a widespread material that is responsible for cholesterol transport in plasma. The concept of employing LDL-modified nanoparticles for tumor-targeted drug delivery has been widely adopted.
Objectives. The objective of this study was to develop and test a new DDS for effective chemotherapy of colorectal cancer.
Material and Methods. We successfully developed an Adriamycin (Adr)-loaded DDS based on LDL-modified SLNs (LDL/SLN/Adr). The tumor-homing property of LDL and the drug-loading capability of SLNs were combined to prepare LDL/SLN/Adr that can specifically deliver Adr to the cancer site to achieve effective chemotherapy of HT-29 colorectal cancer.
Results. In vitro analysis showed that LDL/SLN/Adr consisted of nano-sized particles and was capable of targeting the low-density lipoprotein receptors (LDLR) which were overexpressed in many cancer cell lines. As a result, LDL/SLN/Adr exerted better cytotoxicity than unmodified SLNs and free drugs. In vivo imaging and anticancer assays also confirmed the preferable tumor-homing and enhanced anticancer effect of LDL/SLN/Adr.
Conclusion. LDL/SLN/Adr might be a promising DDS for effective chemotherapy of colorectal cancer.
colorectal cancer, low-density lipoprotein, silica nanoparticles, Adriamycin
- Wang C, Chen S, Yu Q, Hu F, Yuan H. Taking advantage of the disadvantage: Employing the high aqueous instability of amorphous calcium carbonate to realize burst drug release within cancer cells. J Mater Chem B Mater. 2017;5:2068–2073.
- Brown SD, Nativo P, Smith JA, et al. Gold nanoparticles for the improved anticancer drug delivery of the active component of oxaliplatin. J Am Chem Soc. 2010;132(13):4678–4684.
- Slowing II, Vivero-Escoto JL, Wu CW, Lin VS. Mesoporous silica nanoparticles as controlled release drug delivery and gene transfection carriers. Adv Drug Deliv Rev. 2008;60(11):1278–1288.
- Ye Z, Fahrenholtz C, Hackett C, et al. Large‐pore functionalized mesoporous silica nanoparticles as drug delivery vector for a highly cytotoxic hybrid platinum‐acridine anticancer agent. Chemistry. 2017; 23(14):3386–3479.
- Croissant JG, Qi C, Mongin O, et al. Disulfide-gated mesoporous silica nanoparticles designed for two-photon-triggered drug release and imaging. J Mater Chem B Mater. 2015;3:6456–6461.
- Sobot D, Mura S, Couvreur P. How can nanomedicines overcome cellular-based anticancer drug resistance? J Mater Chem B Mater. 2016;4: 5078–5100.
- Li SD, Huang L. Nanoparticles evading the reticuloendothelial system: Role of the supported bilayer. Biochim Biophys Acta. 2009;1788(10): 2259–2266.
- Adumeau L, Genevois C, Roudier L, Schatz C, Couillaud F, Mornet S. Impact of surface grafting density of PEG macromolecules on dually fluorescent silica nanoparticles used for the in vivo imaging of subcutaneous tumors. Biochim Biophys Acta. 2017;1861(6):1587–1596.
- Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol: Modification of low-density lipoprotein that increase its atherogenicity. N Engl J Med. 1989;320(14):915–924.
- Song H, Li Y, Lee J, Schwartz AL, Bu G. Low-density lipoprotein receptor-related protein 1 promotes cancer cell migration and invasion by inducing the expression of matrix metalloproteinase 2 and 9. Cancer Res. 2009;69(3):879–886.
- Nikanjam M, Blakely EA, Bjornstad KA, Shu X, Budinger TF, Forte TM. Synthetic nano-low density lipoprotein as targeted drug delivery vehicle for glioblastoma multiforme. Int J Pharm. 2007;328(1):86–94.
- Dai L, Liu J, Luo Z, Li M, Cai K. Tumor therapy: Targeted drug delivery systems. J Mater Chem B Mater. 2016;4:6758–6772.
- Zhang N, Tao J, Hua H, Sun P, Zhao Y. Low-density lipoprotein peptide-combined DNA nanocomplex as an efficient anticancer drug delivery vehicle. Eur J Pharm Biopharm. 2015;94:20–29.
- Wang C, Li M, Yang T, et al. A self-assembled system for tumor-targeted co-delivery of drug and gene. Mater Sci Eng C Mater Biol Appl. 2015;56:280–285.
- Wu H, Zhao Y, Mu X, et al. A silica-polymer composite nano system for tumor-targeted imaging and p53 gene therapy of lung cancer. J Biomater Sci Polym Ed. 2015;26(6):384–400.
- Zhang Y, Han L, Hu L-L, et al. Mesoporous carbon nanoparticles capped with polyacrylic acid as drug carrier for bi-trigger continuous drug release. J Mater Chem B Mater. 2016;4:5178–5184.
- Yan L, Wang H, Zhang A, Zhao C, Chen Y, Li X. Bright and stable near-infrared pluronic-silica nanoparticles as contrast agents for in vivo optical imaging. J Mater Chem B Mater. 2016;4:5560–5566.
- Gulzar A, Gai S, Yang P, Li C, Ansari MB, Lin J. Stimuli responsive drug delivery application of polymer and silica in biomedicine. J Mater Chem B Mater. 2015;3:8599–8622.
- Antonietti M, Basten R, Lohmann S. Polymerization in microemulsions: A new approach to ultrafine, highly functionalized polymer dispersions. Macromol Chem Phys. 1995;196:441–466.
- Zarur AJ, Ying JY. Reverse microemulsion synthesis of nanostructured complex oxides for catalytic combustion. Nature. 2000;403(6765):65–67.
- Ruff J, Steitz J, Buchkremer A, et al. Multivalency of PEG-thiol ligands affects the stability of NIR-absorbing hollow gold nanospheres and gold nanorods. J Mater Chem B Mater. 2016;4:2828–2241.
- Stoffelen C, Staltari-Ferraro E, Huskens J. Effects of the molecular weight and the valency of guest-modified poly(ethylene glycol)s on the stability, size and dynamics of supramolecular nanoparticles. J Mater Chem B Mater. 2015;3:6945–6952.
- Wang C, Bao X, Ding X, et al. A multifunctional self-dissociative polyethyleneimine derivative coating polymer for enhancing the gene transfection efficiency of DNA/polyethyleneimine polyplexes in vitro and in vivo. Polym Chem. 2015;6:780–796.
- Mazière JC, Mazière C, Emami S, et al. Processing and characterization of the low density lipoprotein receptor in the human colonic carcinoma cell subclone HT29-18: A potential pathway for delivering therapeutic drugs and genes. Biosci Rep. 1992;12(6):483–494.
- Wang J, Wang R, Zhang F, et al. Overcoming multidrug resistance by a combination of chemotherapy and photothermal therapy mediated by carbon nanohorns. J Mater Chem B Mater. 2016;4:6043–6051.