pH-Controlled Gas-Generating Mineralized Nanoparticles: A Theranostic Agent for Ultrasound Imaging and Therapy of Cancers

Abstract

We report a theranostic nanoparticle that can express ultrasound (US) imaging and simultaneous therapeutic functions for cancer treatment. We developed doxorubicin-loaded calcium carbonate (CaCO3) hybrid nanoparticles (DOX-CaCO3-MNPs) through a block copolymer templated in situ mineralization approach. The nanoparticles exhibited strong echogenic signals at tumoral acid pH by producing carbon dioxide (CO2) bubbles and showed excellent echo persistence. In vivo results demonstrated that the DOX-CaCO3-MNPs generated CO2 bubbles at tumor tissues sufficient for echogenic reflectivity under a US field. In contrast, the DOX-CaCO3-MNPs located in the liver or tumor-free subcutaneous area did not generate the CO2 bubbles necessary for US contrast. The DOX-CaCO3-MNPs could also trigger the DOX release simultaneously with CO2 bubble generation at the acidic tumoral environment. The DOX-CaCO3-MNPs displayed effective antitumor therapeutic activity in tumor-bearing mice. The concept described in this work may serve as a useful guide for development of various theranostic nanoparticles for US imaging and therapy of various cancers.

One-step formation of lipid-polyacrylic acid-calcium carbonate nanoparticles for co-delivery of doxorubicin and curcumin

“…The presence of CaCO3 precipitation might control the size of DNA/CaCO3 coprecipitation and enhance gene delivery (Zhao et al, 2014). Moreover, the inherent pHsensitivity of CaCO3 might be useful to promote the dissociation of nanoparticles and endosome/lysosome escape under low pH conditions (Gong et al, 2015, Min et al, 2015. Considering the feasibility of CaCO3 formation in the presence of Ca 2+ and CO3 2-ions, a promising strategy involves including CaCO3 in a DDS as an inducer of drug release.…”

Theranostic Multilayer Capsules for Ultrasound Imaging and Guided Drug Delivery

“…2 Ultrasound (US) imaging encompasses low cost, fast real-time visualization, deep penetration in tissues, and noninvasiveness. 3,4 Importantly, US can trigger drug release via inertial cavitation causing mechanical damage to the drug carriers. 5 Unlike other stimuli, including pH, temperature, and enzymatic degradation, US offers precise control over spatiotemporal drug release and drug transport into solid tumors.…”

“…10,11 However, the clinical potential of US theranostic agents can only be fully realized by combining sufficient US contrast, high encapsulation efficiency, and US-triggered release in one entity. 4,12 Although microbubbles (1–8 µm in size) with perfluorocarbons can provide sufficient US contrast, they easily dissolve in blood, have short half-lives once activated, 8,13 and are challenging for chemical modification and drug loading. 14,15 Liposomes, nanoparticles, and micelles are more stable and easily modifiable but rarely produce US imaging contrast due to their small size.…”

Gas-generating TPGS-PLGA microspheres loaded with nanoparticles (NIMPS) for co-delivery of minicircle DNA and anti-tumoral drugs

“…The micron-size of the NIMPS system may prove beneficial in the future for inclusion in tandem or ovoid devices that are generally used in the clinics to locallyapplytreatment for this particular type of cancer [39]. In addition, the recently described potential of using gas generation fortheranostic applications based in ultrasound imaging further expands the applicability of these carriers [40].…”