Preparation Of PH-Responsive K5 Polysaccharide-Gold Nanocluster For Drug Delivery

Drug nanocarriers which have distinctive dimension, structure and outstanding performance could evade many problems generated by conventional drug carriers, with promising application in terms of drug delivery. This work aimed to develop a series of p H-responsive drug nanocarriers based on K5 polysaccharide, for loading and deliverying hydrophobic anticancer drugs.(1) Preparation of K5 polysaccharide based p H-responsive drug carrier for cancer therapyWe designed and fabricated a series of p H-responsive K5 polysaccharide-histidine conjugates(KHs). These KHs could self-assemble into nanoparticles in the physiological environment and encapsulate model drug Doxorubicin(DOX). Their chemical structures identified by 1H NMR, the degrees of substitution(DS) were calculated to be 20%, 28% and 39%, respectively. The obtained drug-loaded KH nanoparticles(KHD) had uniform size distribution in aqueous solution. Among them, KH3 processed optimal stability and drug loading efficiency. The critical aggregation concentration(CAC) of KH3 was calculated as 23 mg/ L. The size of KH3 and KHD3 were 275.9 nm and 207.7 nm. In vitro drug release sduty of KHD3 revealed apparent p H responsiveness. Cytotoxicity assay showed that KHD3 could effectively transport DOX into cancer cells and showed accelerated DOX release behavior in the acidic milieu. These carriers had favorable biocompatibility and could significantly improve the selectivity of chemotherapy, showing potential in the application of clinical treatment.(2) Preparation of p H-responsive K5 polysaccharide-gold nanocluster for cancer therapyWe prepared ?-cyclodextrin modified gold nanoparticles(CA), for improving the stability and controllability of the system. Through the high affinity between ?-cyclodextrin(CD) and histidine(His) moieties, KH and CA assembled(host-guest assembly) into a novel nanocluster supramolecular conjugates(KA NCs) possessing p H-responsive property for loading DOX. The existence of CA on gold nanoparticles surface were characterized by TGA and FT-IR, and the mass fraction of CD in CA were calculated to be 48%, 56% and 64%, respectively. The size of KA NCs decreased with the increasing of CD/His ratio in the complex, and KA NC made from KH3 has smaller size and PDI. KH3/CA at His: CD molar ratio of 1 : 1 and 2: 1 for loading DOX were further studied for their anticancer activity. Dox loaded KA NCs(KAD NCs) still had a narrow size distribution below the CAC of KH, suggesting that the stability of the system was improved significantly. In vitro cellular uptake assay illustrated KAD NCs could be rapidly internalized into cancer cells. KAD4 NCs exhibited equivalent cytostatic effect as DOX and showed accelerate DOX release behavior in acidic milieu of tumour. In addition, gold nanoparticles incorporated in this system had potential applications in photothermal therapy and diagnosis.In summary, KAD NCs exhibited superior stability, possessed p H-responsive DOX release, and improved selectivity of chemotherapy. Our results indicated that KAD NCs have great potential to be explored as drug carrier in cancer therapy.