Synthesis and Characterization of Multifunctional Nanocomposite Structures for Biomedical Application

Abstract

Inorganic nanoparticles based assembly of ‘all-in-one’ multifunctional nanocomposites has been synthesized for in vitro magnetic resonance imaging, pH sensitive, light-triggered and magnetic field triggered drug release and for combined phototochemotherapy. Development of dual encapsulated antibody-targeted photosensitizing liposomes for in vivo imaging and combined phototochemotherapy is also demonstrated. Superparamagnetic iron oxide nanocomposites (IONCs) were formed through a microwave-assisted green approach using fruits peel extracts as reducing and capping agents. This involves the stabilization of IONCs through co-ordination of different phytochemicals. The IONCs were extensively characterized for structural, elemental, magnetic and physicochemical analysis, and were found physically and chemically stable with a shelf life stability of 20 days, an average size of 23.35 ± 4.99 nm and mean band gap value of 2.8 ± 0.17 eV. IONCs exhibited excellent water dispersibility, colloidal stability and haemocompatibility. High saturation magnetization (58.8 ± 3.08 emu/g) coupled with superparamagnetic property makes IONCs ideal candidates for magnetic hyperthermia and drug delivery application. Relatively high r2 relaxivity 228.25 mM-1 s-1 were found 1.2 folds higher than the commercial Resovist®. Cell viability assay data revealed that PEGylation or carboxylation of these IONCs appear to significantly shield the surface of the particles. Nickel Oxide based core-shell nanoconstruct with Doxorubicin loaded core and folic acid connected BSA shell (NDOX@BSA-FA) induced approximately 5 folds higher cell killing than the NiO through photo triggered DOX release and in vitro ROS production from the NiO core. The entrapped drug from NDOX@BSA-FA was released in sustained way in a pH sensitive environment while a robust release was observed on photoirradiation. The Diphenylbenzofuran (DPBF), Tetrazolium bromide (MTT) cell viability and Thiobarbituric acid reactive substances (TBARs) assays revealed the photodynamic treatment potential of these core shell nanoconstructs. Further, the combined effect of DOX and NiO from NDOX@BSA-FA demonstrated an eight fold higher effective photokilling when compared with the free DOX. The merits of naturally occurring polysaccharides chitosan(CS), carboxymethyl cellulose (CMC) and natural protein bovine serum albumin (BSA) were combined with magnetic NiFe2O4 (NFs) cores and chemotherapeutic drug Paclitaxel (PTX), to design PTX and NFs loaded bionanocomposites (BNC) with folic acid (FA) modified surface for potential biomedical applications. Nontoxicity, hydrophilicity, and cancer-specific capability of these biopolymers endow the magnetic cores with excellent aqueous dispersibility as well as the 2 “stealth” property, which may prolong the circulation time of the BNC in blood stream. These BNC showed superior transversal relaxation rate r2 of 349 mM-1 s-1 along with folate receptor-targeted and magnetically directed functions were found physically and chemically stable over a period of 60 days. Application of an external magnetic field effectively enhanced the PTX release with 2 folds higher selectivity of folate conjugates when compared with nonfolate conjugates. A robust, physically, chemically and optically stable photosensitizing liposomal platform has been successfully developed, comprising hydrophobic photosensitizer, benzoporphyrin derivative molecules within the phospholipid bilayer as a lipid conjugate and surface density of strained cyclooctyne moieties was optimized to mediate copper free click conjugation of photosensitizing liposomes to azido functionalized antibodies. A successful formulation of near infrared deep tissue imaging dyes into antibody-targeted photosensitizing liposomes designed for in vivo tumor imaging has been achieved. Further we developed targeted Lyso Pc-BPD and Carboplatin/Gemcitabine coencapsulated photosensitizing liposomes by loading the chemotherapeutics within antibody targeted photosensitizing liposomal formulations in all aspects of synthesis, characterization, validation and reproducibility for combined chemo and photodynamic therapy. Integration of multifunctional probes and conjugation strategies push the boundaries of combination therapies beyond the conventional monotherapies.