PrPC Aptamer Conjugated–Gold Nanoparticles for Targeted Delivery of Doxorubicin to Colorectal Cancer Cells

Abstract

Anticancer drugs, such as fluorouracil (5-FU), oxaliplatin, and doxorubicin (Dox) are commonly used to treat colorectal cancer (CRC); however, owing to their low response rate and adverse effects, the development of efficient drug delivery systems (DDSs) is required. The cellular prion protein PrPC, which is a cell surface glycoprotein, has been demonstrated to be overexpressed in CRC, however, there has been no research on the development of PrPC-targeting DDSs for targeted drug delivery to CRC. In this study, PrPC aptamer (Apt)-conjugated gold nanoparticles (AuNPs) were synthesized for targeted delivery of Dox to CRC. Thiol-terminated PrPC-Apt was conjugated to AuNPs, followed by hybridization of its complementary DNA for drug loading. Finally, Dox was loaded onto the AuNPs to synthesize PrPC-Apt-functionalized doxorubicin-oligomer-AuNPs (PrPC-Apt DOA). The PrPC-Apt DOA were spherical nanoparticles with an average diameter of 20 nm. Treatment of CRC cells with PrPC-Apt DOA induced reactive oxygen species generation by decreasing catalase and superoxide dismutase activities. In addition, treatment with PrPC-Apt DOA inhibited mitochondrial functions by decreasing the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, complex 4 activity, and oxygen consumption rates. Compared to free Dox, PrPC-Apt DOA decreased proliferation and increased apoptosis of CRC cells to a greater degree. In this study, we demonstrated that PrPC-Apt DOA targeting could effectively deliver Dox to CRC cells. PrPC-Apt DOA can be used as a treatment for CRC, and have the potential to replace existing anticancer drugs, such as 5-FU, oxaliplatin, and Dox.

Recent Advances of Mesoporous Silica as a Platform for Cancer Immunotherapy

“…The use of nanoparticles can improve biodistribution, pharmacokinetics, and efficacy of therapeutic agents [ 5 , 6 ]. There are a variety of nanoparticles that have been employed as a nanocarrier, such as polymeric nanoparticles [ 7 , 8 , 9 ], dendrimers [ 10 , 11 , 12 ], liposomes [ 13 , 14 , 15 ], metallic nanoparticles [ 16 , 17 ], and other inorganic nanoparticles [ 18 , 19 , 20 ]. Recently, inorganic nanoparticles have garnered increased interest as a DDS, with mesoporous silica being a relatively new material for study and research.…”

Aptamer-conjugated gold nanoparticles and their diagnostic and therapeutic roles in cancer

“…Presently, various fitness-based diagnoses are also in full swing in preclinical research and clinical trials. Adapters combined with AuNPs can be used for targeted drug therapy and photothermal therapy of cervical cancer( Li M et al, 2021 ), lung cancer( Yang Y et al, 2021 ), and colorectal cancer( Go et al, 2021 ) by carrying drugs or using the optical properties of AuNPs, thereby reducing the side effects on normal tissues. In conclusion, aptamers have a wide range of physical and biochemical properties that demonstrate their potential as both diagnostic tools and therapeutic agents, and can be considered as suitable application prospects in clinical disease diagnosis and treatment.…”

“…Simultaneously, AuNPs has unique surface plasmon resonance (SPR) and adjustable surface functionality (fluorescent dyes, redox markers, and other chemical modifications can be easily carried out on AuNPs), because of which the detection results can be visualized using not only immunosensors but also computed tomography images, microscopy, and additional techniques ( Jimenez et al, 2019 ; Liao et al, 2019 ; Chakraborty et al, 2021 ). For cancer treatment, the active targeting of aptamers can more accurately select target cells to assist in the controlled and continuous transfer of therapeutic molecules (drugs ( Go et al, 2021 ) and peptides ( Kim et al, 2015 )) using AuNPs and improve the uptake of therapeutic molecules by the cells. It is worth noting that the unique photothermal conversion characteristics of AuNPs makes it a suitable photosensitizer for the photothermal treatment of colorectal cancer and additional tumours( Chugh et al, 2018 ; Wang et al, 2021 ).…”

Nanotechnology in Colorectal Cancer for Precision Diagnosis and Therapy

“…The result revealed that in comparison with free Dox treatment, the oligomer PrPC-Apt DOA decreased the growth and increased the apoptosis of CRC cells to a significant extent. This indicated the possibility of the application of PrPC-Apt DOA as a therapeutic agent for CRC (Go et al, 2021). The gold nanoparticles (GNPs) may also be used to enhance the anticancer efficacy of 5-FU and reduce its side effects.…”