pH-Responsive Nanocarriers for Cancer Therapy

Kalmouni, Mona (2022). pH-Responsive Nanocarriers for Cancer Therapy. PhD thesis The Open University.



There are currently several strategies that are used to treat cancer including surgery, chemotherapy and radiotherapy. However, conventional chemotherapeutics suffer from a number of limitations, such as poor solubility, short in vivo circulation half-life and lack of specificity. To address these issues, researchers have developed nanocarriers for the safer and more effective delivery of chemotherapeutics to cancer cells. Despite rapidly growing interest in developing nanocarriers as chemotherapeutic drug delivery vehicles, their use in a clinical setting has been hindered by their targeting inefficiency, inability to traverse the plasma membrane, poor circulation stability and becoming entrapped in endocytic or lysosomal compartments. In light of this, cell-penetrating peptides (CPPs) have received considerable attention due to their ability in mediating the efficient transport of nanoparticles (NPs) across the semi-permeable plasma membrane. While these CPPs show great potential in vitro, their lack of target specificity remains a major obstacle to their clinical application. Researchers have instead developed strategies in which cancer targeting peptides (CTPs) that exploit the unique characteristics of the tumor microenvironment or cancer cells are used in order to improve cancer cell specificity of the coupled nanocarriers. In these studies, pH-responsive organic and inorganic nanocarriers were designed that were shown to be biocompatible and exhibit highly controlled drug release behavior. These nanocarriers were specifically targeted and internalized into cancer cells within the acidic tumor microenvironment owing to the novel pH-responsive acidity-triggered rational membrane (ATRAM) peptide present on the surface of the NPs. Moreover, in vitro cell viability studies showed remarkable cytotoxicity of the nanocarriers in cancer cells. Additionally, treatment with ATRAM-coupled NPs effectively reduced the tumor volume and mass, while exhibiting no toxicity to healthy tissue. Taken together, these results demonstrate that the novel ATRAM-coupled high stability nanocarriers are potential candidates for safer and more effective drug delivery for cancer therapy.

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