In Situ Synthesis of Fluorescent Mesoporous Silica–Carbon Dot Nanohybrids Featuring Folate Receptor-Overexpressing Cancer Cell Targeting and Drug Delivery

Abstract

HIGHLIGHTS• A one-pot method was developed for the preparation of fluorescent mesoporous silica nanoparticles-carbon dots (MSNs-CDs) nanohybrid.• The MSNs-CDs nanohybrid showed stable and bright yellow emission, excellent biocompatibility, and specific targeting capability toward folate receptor-overexpressing cancer cells and can be applied as fluorescence imaging-guided drug carriers for effectively delivering anticancer drugs to tumor sites.ABSTRACT Multifunctional nanocarrier-based theranostics is supposed to overcome some key problems in cancer treatment. In this work, a novel method for the preparation of a fluorescent mesoporous silica-carbon dot nanohybrid was developed. Carbon dots (CDs), from folic acid as the raw material, were prepared in situ and anchored on the surface of amino-modified mesoporous silica nanoparticles (MSNs-NH 2 ) via a microwave-assisted solvothermal reaction. The as-prepared nanohybrid (designated MSNs-CDs) not only exhibited strong and stable yellow emission but also preserved the unique features of MSNs (e.g., mesoporous structure, large specific surface area, and good biocompatibility), demonstrating a potential capability for fluorescence imagingguided drug delivery. More interestingly, the MSNs-CDs nanohybrid was able to selectively target folate receptor-overexpressing cancer cells (e.g., HeLa), indicating that folic acid still retained its function even after undergoing the solvothermal reaction. Benefited by these excellent properties, the fluorescent MSNs-CDs nanohybrid can be employed as a fluorescence-guided nanocarrier for the targeted delivery MSNs-CDs@DOX Cancer cell targeted delivery Endocytosis DOX release FL imaging Enhanced chemotherapy FA receptor Cytoplasm N u c le u s pH of anticancer drugs (e.g., doxorubicin), thereby enhancing chemotherapeutic efficacy and reducing side effects. Our studies may provide a facile strategy for the fabrication of multifunctional MSN-based theranostic platforms, which is beneficial in the diagnosis and therapy of cancers in future.

Recent advance of carbon dots in bio-related applications

“…The heat generated by laser light by the complexes easily damage the cells which triggered the release of DOX from complexes. Prasad et al [162,163] used mesoporous silica nanoparticles as a carrier. DOX and CDs were loaded into the mesoporous silica nanoparticles and conjugated FA on the surface of nanoparticles.…”

Multimodal Decorations of Mesoporous Silica Nanoparticles for Improved Cancer Therapy

“…In mostly 80–90% of epithelial ovarian cancers, other gynecological cancers, lung cancers and breast cancers, the FRα is highly overexpressed and gaining increasing importance to be exploited for targeted cancer therapy [ 81 ]. Considering this fact, several research groups have reported the enhanced specific cellular uptake of MSN in various cancer cells, having overexpressed folate receptors by modifying MSN surface with folic acid [ 82 , 83 , 84 , 85 , 86 ]. Nonetheless, using two different human pancreatic cancer xenografts on different mouse species, Lu et al have also shown dramatic improvements in tumor-suppression effect by using folic acid functionalized camptothecin-loaded MSN in comparison with unfunctionalized MSN [ 87 ].…”

“…Functionalized QD-embedded MSN with high quantum yield have been largely exploited for selective tumor imaging in vivo, as well as for cancer cell imaging and detection in vitro by the intracellular internalization of QDs [ 278 , 279 ]. Recently, Zhao et al have reported the synthesis of fluorescent Carbon Dot-MSN nanohybrids [ 86 ]. Nevertheless, Cheng et al have reported tri-functionalized MSN, effectively decorated to be used in the field of theranostics coordinating the trio of target, imaging, and therapy in a discrete entity [ 280 ].…”

Recent developments in the use of organic–inorganic nanohybrids for drug delivery

“…The results indicated that SONH has higher drug loading ability where about 97% of the drug is released in a lower pH over 7 days in contrast to 20% release at neutral pH. In addition, multifunctional fluorescent mesoporous amine functionalized SONH decorated with folate receptors (MSN–CDs) has been developed to allow image guided delivery of DOX into folate receptor overexpressing HeLa cells (S. Zhao et al, ). Codelivery of drugs with small interfering RNA (siRNA), targeting the pump P‐gp can overcome issues pertaining to MDR.…”