Smart responsive-calcium carbonate nanoparticles for dual-model cancer imaging and treatment

Calcium carbonate: controlled synthesis, surface functionalization, and nanostructured materials

“…Thirdly, the combination of pH-sensitive gasgenerating CaCO 3 NPs with imaging contrast agents such as elements or organic fluorophores, bioimaging contrast agents for US imaging, MRI, fluorescence imaging, and multimodal imaging agents can be constructed for use in medical diagnosis (Table 3). 56 Fourthly, CaCO 3 functionalized using lipids or polymers shows enhanced physical stabilization and can act as a binding site for targeting agents to form porous or coreshell nanocarriers for use in oncosis, chemotherapy, PDT, and PTT. 220,221 In addition, pH-sensitive CO 2 -generating CaCO 3 NPs can be loaded with anticancer drugs and imaging agents, as a designed novel nanotheranostic platform for use in US imaging-guided chemotherapy and PDT, 222,223 MRI-guided chemotherapy, and fluorescence imaging-guided chemotherapy and PDT.…”

“…4.5.3 Fluorescence imaging and therapy. CaCO 3 -Based nanocomposites with a combination of drug-loaded CaCO 3 and inorganic nanomaterials (carbon dots) or organic fluorophores (e.g., tetracycline, 44 Ce6, 42 and ICG 56 ) can be activated by tumor-specific endogenous stimuli. For instance, a porous carbon dot-PAA-CaCO 3 nanocomposite has been designed 293 in which the fluorescent carbon dots not only serve as a template for the crystallization and assembly of CaCO 3 , but also have fluorescence properties and are very small in size.…”

“…Thus, gas-generating CaCO 3 NPs may overcome the limitations of currently used gas-filled microbubbles such as perfluorocarbons. 56 The pH-sensitive CaCO 3 NPs continuously generate CO 2 nanobubbles that coalesce into microbubbles, allowing for the persistent strong echogenic US imaging. 222 For instance, a CaCO 3 -based US imaging agent (CaCO 3 AlgNC) that is stable in serum-containing media was prepared by encapsulating CaCO 3 NPs in a flexible and biocompatible alginate-loaded pluronic-based nanocarrier (AlgNC).…”

“…48 To date, CaCO 3 has been used in many therapeutic and theranostic applications in chemotherapy, photothermal therapy (PTT), or photodynamic therapy (PDT); 49,50 wound healing and blood clotting; 51,52 in ultrasound (US), 53,54 fluorescence, 44 or magnetic resonance imaging (MRI); 55 and multimodal imaging and therapy. 56,59,60 In addition to the above-mentioned aspects of crystalline CaCO 3 , the preparation and stabilization of ACC have also presented a challenge. Although several synthetic routes to ACC inspired by and based on biomineralization have been developed, [57][58][59] those processes are sophisticated.…”

“…combined with ICG can allow the integration of US and fluorescence imaging into one diagnostic nanoplatform for dualmodality imaging-guided therapy. To this aim, CaCO 3 NPs were encapsulated with DOX and ICG to form CaCO 3 -DOX/ICG NPs 56. The smart pH-responsive CaCO 3 -DOX/ICG NPs were shown to significantly inhibit tumor growth enhanced US imaging by triggering the effective release of DOX with CO 2 bubble generation under an acidic TME.…”