We propose to develop multifunctional, targeted nano-photomedicines that are capable of bypassing biological barriers to deliver nano-engineered photosensitizer drugs and molecular-imaging agents to tumor tissues and angiogenetic micro-vasculature. Specifically, a unique nanomedicine system for targeted multi-spectral photodynamic therapy is proposed. The system consists of (i) luminescent quantumdot (QD) conjugated with photosensitizer (PS) drugs, which can be sensitized at its maximum efficiency using radiations of deep-tissue penetration (ii) molecular-imaging agents for the early stage detection and in situ treatment-effect analysis (iii) active targeting ligands to specifically target tumor and micro-vasculature. During the incoming phase, QDs of ZnS, Y2O3 and Gd2O3 emitting multi-spectral light under excitation with deep high-tissue penetrating radiations will be conjugated with PS so as to sensitize them at their characteristic absorption using Fluorescent Resonant Energy Transfer (FRET). The QD-PS will be combined with MRI contrast agents using `core/shell’ nanotechnology and made water soluble by capping with polyethylene glycol (PEG). Finally, the nanomedicine will be connected with tumor specific ligands such as folic acid, MAbs and peptides. Optimization of nanomedicine will be carried out by studying dark and photo-toxicity in normal and cancer cell-lines in vitro. Photodynamic treatment will be carried out in pre-clinical animal models using multispectral radiations under different photo- and drug-dose conditions, followed by molecular imaging (MRI) based estimation of PDT response-dose inter-relationships. During the return phase, scanning probe imaging based investigations on the mechanism-of-activity of nano-photomedicines at intra-cellular regions leading to cell-death (apoptosis) will be investigated.
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