Porphyrin-based Nanosystems For Improving Photodynamic Therapy By Combining Sonodynamic/Chemotherapy

Annual global health statistics identify cancer among the leading causes of morbidity and mortality,thereby emphasizing the need to develop new effective anti-cancer therapies.Among the various burgeoning anti-cancer therapies,such as immunotherapy,and gene therapy novel photodynamic therapy?PDT?still manifests as an effective treatment strategy for a variety of tumors.Such nonradiative conversion of light energy to ROS generation has been intensively implemented in clinics for the tumor diagnosis and treatment mainly due to its non-ionizing nature,minimal risk of treatment resistance despite repeated exposures and facility to allow combination with other therapeutic procedures.However,clinically used small-molecular photosensitizers?PSs?for PDT share similar disadvantages when used directly in vivo:short blood circulation time,low-tumor targeting efficacy life-threatening phototoxicity,poor solubility in an aqueous medium,and limited light penetration.Therefore,the present study capitalizes on the approaches to enhance the treatment outcomes of PDT of cancer by improving the accumulation of PSs via different novel carrier-mediated systems and by using the mechanism-based combination therapies.These two major research aims are achieved under three major research objectives:?i?Development of sub-10nm sized silica nanoparticles?core-shell silica dots;PSDs?for efficient delivery of a water-soluble PS?porphyrin;TPPS3-NH₂?with the aim to potentiate their accumulation in the tumor for enhanced fluorescence imaging-guided PDT;?ii?Tailoring PSDs for cooperative enhancement interaction of sonodynamic therapy and PDT?referred as SPDT?,and?iii?Co-encapsulation of chemotherapeutic drug doxorubicin?DOX?and porphyrin in a single nanocarrier?PGL-DOX NPs?for fluorescence imaging-guided synergistic chemo-photodynamic.The research objective has been successfully met by formulating two different compositions of porphyrin-based nanoformulations:?i?ultra-small silica NPs covalently encapsulating water-soluble porphyrin,and?ii?PGL NPs self-assembled with a chemotherapeutic drug,DOX and thoroughly utilized for improving therapeutic efficacy against cancer.Besides,we have further utilized NIRF imaging-guided techniques for improving therapeutic efficiency.In brief,we investigated and implemented the carrier-mediated nanosystems and combination therapeutic approaches to complement the photodynamic efficiency of porphyrin-based nanoformulations and demonstrated its use as a multifunctional imaging/therapeutic agent for cancer theranostics.We anticipate that the proposed methodology emancipates limitations and challenges of pre-existing therapeutic systems and provide a new impetus to improve the efficacy of non-invasive therapeutic modalities together with the nanotechnological perspective.