Preparation Of Photo-responsive Microcapsule And Its Application In Photodynamic Treatment

In recent years the photodynamic therapy (PDT) has received extensive attention in theory research and clinical applications as a cancer treatment modality, owing to its advantages, such as good tumor targeting, safety, and local therapeutic effect. PDT depends largely on the effects of photosensitizers (PSs). However the poor water solubility of many PS drugs e.g. porphyrin derivatives, has hampered the successful preclinical and clinical PDT. To overcome this issue, diverse hydrophilic delivery vehicles such as gels, liposomes and colloids were introduced by accumulating encapsulated PSs at affected location to enhance the photodynamic effects of PSs. Recently, hydrophilic polyelectrolyte (PE) microcapsules, constructed by the layer-by-layer (LbL) self-assembly method, have received particular attention due to their unique controllability of size, shape, and permeability, as well as large inner space able to encapsulate drug molecules PE microcapsules have a promising potential in the fields from biology to medicine. With the development of LbL self-assembly technology, biodegradable and biocompatible microcapsules with special properties (i.e. photo-responsive, magnetic-responsive and targeted) have received widespread interest, especially in drug delivery and controlled release. In addition, the micron-grade size also is helpful for various instrument characterizations. Biodegradable microcapsules composed of alginate sodium (ALG)/chitosan (CHI) have been evidenced to be a promising vehicle for loading and controlled release of drugs. In this work, we fabricated a novel photoresponsive microcapsule via the LbL self-assembly technique, in which rose bengal (RB) with high quantum yield of 1O2 was first grafted to CHI chains in a stable chemical bond format, followed by alternatively assembling of ALG and CHI/RB grafted-CHI (RB-CHI) on dissolvable templates and subsequent removal of cores. The PDT effects of capsules (ALG/CHI)4(ALG/RB-CHI) serving as a photo-resposive drug carrier was studied. The research content and the innovative achievements in this paper are divided into the following:(1) The Rose Bengal-grafted chitosan (RB-CHI) synthesized via the dehydration between amino and carboxyl functional groups under mild condition were successfully coated onto the outer layer of preformed biodegradable microcapsules consisting of alginate sodium and chitosan. We have retained the responsive therapeutic effect and avoided the leak-out of RB through the pre-immobility of RB.(2) Using MF as template, we have assembled photo-responsive capsules composed of (ALG/CHI)4(ALG/RB-CHI) via LbL technology, resulting in homogeneous particle diameter (about 3μm) and good dispersal.(3) We have combined microcapsule techniques and PDT together, constructing a drug delivery system for effective accumulation of photosensitizers and targeted anti-tumor cells. The generation of 1O2 originating from the resulting photoresponsive microcapsules upon exposure to light at appropriate wavelength was investigated by electron spin-resonance (ESR) as well as a chemical approach. The quantum yield of 1O2 was tested to be 0.38 (a relatively high level).The phototoxic effects of photo-responsive capsules on human breast adenocarcinoma (MCF-7) cells upon irradiation demonstrated that this system has good biocompatibility and efficient PDT effects, which indicating photo-responsive capsules a potential PDT drug deliver carrariers.