Laser Responsive Cisplatin-Gold Nano-Assembly Synergizes the Effect of Cisplatin With Compliance.

Cisplatin therapy faces low bioavailability and clastogenic potential limitations. Early payload leakage of nanocarriers may impair adequate therapeutic efficacy. We propose encapsulation of cisplatin in such nanocarrier that can be externally stimulated for high payload release and enhanced toxicity at site of action. Cisplatin conjugated gold nanorods (Pt-AuNRs) have been synthesized and characterized through UV visible spectroscopy, dynamic light scattering and transmission electron microscopy. Physico-chemical characterization through X-ray photon spectrometry confirms the covalent linkage between linker and aquated cisplatin with AuNRs. Laser exposure (850 nm, CW) enabled ~15-fold payload release from Pt-AuNRs nano-assembly, which is quite high (P < 0.0001) compared to non-stimulated conditions. The median growth inhibitory concentration (GI50) after laser exposure of Pt-AuNRs was ~11- and 13-fold low compared to corresponding Pt-AuNRs without laser exposure and cisplatin respectively, in sarcoma cells. Synergistic therapeutic difference is more significant (P < 0.01), at lower concentrations of Pt-AuNRs (0.5-10 µg/mL). Pt-AuNRs photothermal therapy indicates a convincible association of over-production of reactive oxygen species (P < 0.0001) and synergistic therapeutic efficacy. Clastogenic potential is found non-significant for Pt-AuNRs (10 µg/mL). Cisplatin nanoconjugate shows biocompatibility against blood cells. In conclusion, laser-stimulated Pt-AuNRs appear a promising drug delivery with synergistic toxic potential against cancer while attenuating cisplatin toxicity.

Doxorubicin-loaded quaternary ammonium palmitoyl glycol chitosan polymeric nanoformulation: uptake by cells and organs.

PURPOSE: This study was aimed to develop doxorubicin-loaded quaternary ammonium palmitoyl glycol chitosan (DOX-GCPQ) nanoformulation that could enable DOX delivery and noninvasive monitoring of drug accumulation and biodistribution at tumor site utilizing self-florescent property of doxorubicin. MATERIALS AND METHODS: DOX-GCPQ amphiphilic polymeric nanoformulations were prepared and optimized using artificial neural network (ANN) and characterized for surface morphology by atomic force microscopy, particle size with polydispersity index (PDI), and zeta potential by dynamic light scattering. Fourier transformed infrared (FTIR) and X-ray diffractometer studies were performed to examine drug polymer interaction. The ANN-optimized nanoformulation was investigated for in vitro release, cellular, tumor, and tissue uptake. RESULTS: The optimized DOX-GCPQ nanoformulation was anionic spherical micelles with the hydrodynamic particle size of 97.8±1.5 nm, the PDI of <0.3, the zeta potential of 28±2 mV, and the encapsulation efficiency of 80%±1.5%. Nanoformulation demonstrated a sustained release pattern over 48 h, assuming Weibull model. Fluorescence microscopy revealed higher uptake of DOX-GCPQ in human rhabdomyosarcoma (RD) cells as compared to free DOX. In vitro cytotoxicity assay indicated a significant cytotoxicity of DOX-GCPQ against RD cells as compared to DOX and blank GCPQ (P<0.05). DOX-GCPQ exhibited low IC50 (1.7±0.404 µmol) when compared to that of DOX (3.0±0.968 µmol). In skin tumor xenografts, optical imaging revealed significantly lower DOX-GCPQ in heart and liver (P<0.05) and accumulated mainly in tumor (P<0.05) as compared to other tissues. CONCLUSION: The features of nanoformulation, ie, small particle size, sustained drug release, and enhanced cellular uptake, potential to target tumor passively coupled with the possibility of monitoring of tumor localization by optical imaging may make DOX-GCPQ an efficient nanotheranostic system.