Hypocrellin A-cisplatin-intercalated hectorite nano formulation for chemo-photodynamic tumor-targeted synergistic therapy

Hectorite is trioctahedral clay mineral that possess unique characteristics of surface reactivity and adsorption, cation exchange capacity and easy delamination in water into individual nano layers. Thus, hectorite can be a promising nanocarrier with biocompatibility, high payload and controlled release of drug. Therefore, in the present study, hectorite has been used for the delivery of two hydrophobic molecules; chemotherapeutic drug DDP [Cis-diamminedichloroplatinum (II)] and natural photosensitizer hypocrellin A (HA) for combinatorial therapy. The experimental results has been fitted to l-type (Langmuir) adsorption isotherm. The adsorption isotherm showed higher affinity of DDP toward the hectorite with almost comparable CEC value of initial silicate layer of hectorite. The loading of drug into nanoclay was further characterize by using SEM, FTIR, XRD, DLS and TGA, which suggest the presence of DDP molecules in between the interparticle and photosensitizer on the surface of nanoclay. After, adsorption the characteristic properties such as photostability and photobleaching of HA has been significantly improved. The photobleaching efficiencies of free HA and Ht-DDP-HA was 72.8 and 55.2%, respectively, and the 1O2 generation quantum yield was 0.86. The in vitro release rate is twofold higher in the presence of laser light and ultrasonic waves. The drug release profile was found to be best fitted by Higuchi square root model, which implicate that release of drug from matrix as square root of time-dependent process and diffusion controlled. The in vitro efficacy of Ht-DDP-HA showed the potent anti-cancerous ability due to combinatorial effect by 2.01 and 1.69 fold times higher efficacy than free DDP and HA, respectively. Flow cytometry data shows the synergistic effect of combined therapy by showing maximum apoptotic and necrotic percentage.