Abstract
Natural melanin nanoplatforms have attracted attention in molecular imaging. Natural melanin can be made into small-sized nanoparticles, which penetrate tumor sites deeply, but unfortunately, the particles continue to backflow into the blood or are cleared into the surrounding tissues, leading to loss of retention within tumors. Here, we report a pH-triggered approach to aggregate natural melanin nanoparticles by introducing a hydrolysis-susceptible citraconic amide on the surface. Triggered by pH values lower than 7.0, such as the tumor acid environment, the citraconic amide moiety tended to hydrolyze abruptly, resulting in both positive and negative surface charges. The electrostatic attractions between nanoparticles drove nanoparticle aggregation, which increased accumulation in the tumor site because backflow was blocked by the increased size. Melanin nanoparticles have the natural ability to bind metal ions, which can be labeled with isotopes for nuclear medicine imaging. When the melanin nanoparticles were labeled by 68Ga, we observed that the pH-induced physical aggregation in tumor sites resulted in enhanced PET imaging. The pH-triggered assembly of natural melanin nanoparticles could be a practical strategy for efficient tumor targeted imaging.
Highlights
With the continuing development of nanotechnology, there is still strong demand for the design of new nanoparticles that have the properties of biocompatibility, long circulation time, low immune response, low toxicity, and biodegradability for biomedical applications (Jiao et al, 2018; Yang et al, 2019; Ou et al, 2020)
We ascertained that the pH-triggered assembly of natural melanin nanoparticles could result in enhanced PET imaging, which could be a practical strategy for efficient tumor imaging
After exposure to an acidic environment, the surface charge of pH-Sensitive Melanin Nanoparticles (pH-MNPs) shifted to a positive value (4.9 ± 0.3 mV), indicating the citraconic amide moieties had been hydrolyzed into protonated amine groups
Summary
With the continuing development of nanotechnology, there is still strong demand for the design of new nanoparticles that have the properties of biocompatibility, long circulation time, low immune response, low toxicity, and biodegradability for biomedical applications (Jiao et al, 2018; Yang et al, 2019; Ou et al, 2020). Nanoparticles about 100 nm in size have been reported to have good retention but still high accumulation in the liver and pancreas before reaching the tumor, resulting in relatively low drug concentrations at the tumor site (Jain and Stylianopoulos, 2010; Albanese et al, 2012). To overcome these limitations, we introduce a pHtriggered approach to aggregate small-sized melanin nanoparticles (pH-MNPs). The MNPs are redecorated with hydrolysis-susceptible citraconic amide, which can maintain a small size in the blood When they reach the tumor site, spontaneous aggregation occurs in response to the tumor’s acidic microenvironment. We ascertained that the pH-triggered assembly of natural melanin nanoparticles could result in enhanced PET imaging, which could be a practical strategy for efficient tumor imaging
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