Preparation Of Laponite Clay Nanoparticle-based Multifunctional Anticancer Drug Carriers For Antitumor Therapy Applications

Most of the currently used anticancer drugs lack sufficient water solubility, have limitedbioavailability, and display non-specificity, fairly limiting their clinical applications. Foreffective cancer therapy applications, it is essential to develop a carrier system that is able toimprove the water solubility of the drug and enables targeted delivery of the drug to cancer cellsvia a receptor-mediated targeting pathway. Among numerous nanoscale carrier systems, Laponite(LAP) is regarded as a novel platform with high encapsulating rate of anticancer drug andbrilliant stability under physiological conditions. Given that LAP itself is non-specific to cancercells, it is essential to develop targeted LAP nanodisks for anticancer drug delivery.In this research, LAP nanodisks were functionalized with folic acid (FA) for targetedanticancer drug delivery. In this approach, LAP nanodisks were first modified with3-aminopropyldimethylethoxysilane (APMES) to render them with abundant amine groups,followed by conjugation with FA or PEGlyted (PEG stands for polyethylene glycol) FA via EDCchemistry. The formed LM-FA and LM-PEG-FA nanodisks were subsequently utilized fordoxorubicin (DOX) loading with impressive encapsulation efficiency of92.1±2.2%and89.6±1.6%, respectively. In vitro drug release profile under different pH conditions show thatDOX is able to be sustained released from LM-FA/DOX and LM-PEG-FA/DOX complexes witha relatively higher release rate under acidic pH conditions than under physiological pHconditions. The synthesized LM-FA/DOX and LM-PEG-FA/DOX complexes displayednon-compromised therapeutic efficacy. The formed LM-FA/DOX and LM-PEG-FA/DOXcomplexes were able to specifically target cancer cells overexpressing high-affinity FA receptorsas confirmed via flow cytometric analysis and confocal microscopic observation. Importantly,LM-PEG-FA/DOX can accelerate the tumor necrosis, inhibit the growth of SK-OV-3solid tumor,and prolong the survival time of tumor-bearing mice. With a relatively lower toxicity to normalorgans, the LM-PEG-FA/DOX complexes can be metabolized thoroughly at two weekspostinjection. The developed nanocarrier system hold great promise to be used for effectivetargeted cancer therapy applications.