Although it's pharmacological effect for cancer therapy, conventional chemotherapy has been compromised by a series of shortcomings such as limited stability, nonspecific tumour targeting ability and severe toxic side effects. To overcome these limitations, multifunctional targeted drug delivery systems for combinatorial therapeutics have been widely explored as novel cancer therapy strategies, showing encouraging results in many pre-clinical animal experiments. Among them, synergistic phototherapy and chemotherapy have demonstrated their abilities to enhance therapeutic efficacies and reduce unwanted side effects via a variety of mechanisms. In this review, we will summarize the latest progress in the development of targeted drug delivery systems with combinations of phototherapy and chemotherapy and discuss the important roles of phototherapy agents involved in those non-conventional therapeutic strategies.
Background: Although dynamics and uses of modified nanoparticles (NPs) as orally administered macromolecular drugs have been researched for many years, measures of molecule stability and aspects related to important transport-related mechanisms which have been assessed in vivo remain as relatively under characterized. Thus, our aim was to develop a novel type of oral-based delivery system for insulin and to overcome barriers to studying the stability, transport mechanisms, and efficacy in vivo of the delivery system. Methods: NPs we developed and tested were composed of insulin (INS), dicyandiamidemodified chitosan (DCDA-CS), cell-penetrating octaarginine (r8), and hydrophilic hyaluronic acid (HA) and were physically constructed by electrostatic self-assembly techniques. Results: Compared to free-insulin, levels of HA-DCDA-CS-r8-INS NPs were retained at more desirable measures of biological activity in our study. Further, our assessments of the mechanisms for NPs suggested that there were high measures of cellular uptake that mainly achieved through active transport via lipid rafts and the macropinocytosis pathway. Furthermore, investigations of NPs indicated their involvement in caveolae-mediated transport and in the DCDA-CS-mediated paracellular pathway, which contributed to increasing the efficiency of sequential transportation from the apical to basolateral areas. Accordingly, high efficiency of absorption of NPs in situ for intestinal loop models was realized. Consequently, there was a strong induction of a hypoglycemic effect in diabetic rats of NPs via orally based administrations when compared with measures related to free insulin. Conclusion: Overall, the dynamics underlying and influenced by HA-DCDA-CS-r8-INS may hold great promise for stability of insulin and could help overcome interference by the epithelial barrier, and thus showing a great potential to improve the efficacy of orally related treatments.
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