For cancer therapy, pH-sensitive micro-/nanofibres have been fabricated as they can effectively achieve acid-responsive drug release and their 3D fibrous structure can support tissue regeneration. Current pH-sensitive linkers or valves in the fibrous systems are usually made of polymeric macromolecules, which suffer from slow response to pH changes and delayed drug release, limiting their applicability in highly dynamic tumour environment. Moreover, such systems may release drugs at physiological pH, possibly leading to damaged normal tissues, decreased blood cell production or lower immunity.

To tackle this problem, our team at the Interdisciplinary Division of Biomedical Engineering at the Hong Kong Polytechnic University has developed a promising and facile acid-responsive controlled drug release system in which 'CaCO3 inorganic gates' block the pore openings of drug-loaded mesoporous silica nanoparticles (MSNs), which are encapsulated inside poly-l-lactide (PLLA) fibres. When local pH drops below physiological level, the 'inorganic gates' undergo a rapid reaction with the secreted acid to produce CO2 gas (CaCO3 + 2H+ → Ca2+ + H2O + CO2↑), which facilitates water penetration into the fibre's inner core as well as drug release, significantly inhibiting cancer cell survival for a long period. Using such 'inorganic gates' is particularly advantageous over organic ones because they overcome the issue of limited or slow drug release under a fibre environment with low liquid content. Moreover, the capping effect of CaCO3 gates under physiological pH limits the cytotoxicity of loaded drugs to healthy tissues. Additionally, the initial burst release could be finely controlled and the bioactivity of loaded drugs could be well-reserved due to the drug encapsulation in the MSNs.

Such drug release system manipulates the acidic nature of cancer and serves as an excellent example of disease-triggered therapy. It minimises damage to healthy cells at physiological pH but effects long-term drug release to combat cancer cells when the targeted tissue environment becomes acidic. Simultaneously, it can support normal tissue regeneration at tumour resection sites due to its 3D structure, which mimics the extracellular matrix. Ultimately, this new therapeutic strategy may be widely applicable in cancer treatment that requires long-term drug release in order to suppress cancerous tissues without inhibiting normal tissue repair and regeneration after tumour resection.

This article is contributed by Dr Xin Zhao, assistant professor of the Interdisciplinary Division of Biomedical Engineering at the Hong Kong Polytechnic University; with the coordination of the Biomedical Division.