Crosslinked albumin-manganese nanoaggregates with sensitized T1 relaxivity and indocyanine green loading for multimodal imaging and cancer phototherapy

Albumin-manganese-based nanocomposites (AMNs) characterized by simple preparation and good biocompatibility have been widely used for in vivo T-1-weighted magnetic resonance imaging (MRI) and cancer theranostics. Herein, an aggregation and crosslinking assembly strategy was proposed to achieve the sensitization to T-1 relaxivity of the albumin-manganese nanocomposite. At a relatively low Mn content (0.35%), the aggregation and crosslinking of bovine serum albumin-MnO2 (BM) resulted in a dramatic increase of T-1 relaxivity from 5.49 to 67.2 mM(-1) s(-1). Upon the loading of indocyanine green (ICG) into the crosslinked BM nanoaggregates (C-BM), the T-1 relaxivity of the C-BM/ICG nanocomposite (C-BM/I) was further increased to 97.3 mM(-1) s(-1), which was much higher than those reported previously even at high Mn contents. Moreover, the presence of C-BM greatly enhanced the photoacoustic (PA) and photothermal effects of ICG at 830 and 808 nm, respectively, and the second near infrared fluorescence (NIR-II FL) of ICG also showed better stability. Therefore, the synthesized C-BM/ICG nanocomposite exhibited remarkable performance in in vivo multimodal imaging of tumors, such as T-1-weighted MRI, NIR-II FL imaging and PA imaging, and cancer phototherapy with little side effects. This work provided a highly efficient and promising multifunctional nanoprobe for breaking through the limits of cancer theranostics, and opened a new avenue for the development of high-relaxivity AMNs and multimodal imaging methodology.