Transcytosis-Inducing Multifunctional Albumin Nanomedicines with Deep Penetration Ability for Image-Guided Solid Tumor Treatment.

Transcytosis is an active transcellular transportation pathway that has garnered interest for overcoming the limited deep penetration of nanomedicines in solid tumors. In this study, a charge-convertible nanomedicine that facilitates deep penetration into solid tumors via transcytosis is designed. It is an albumin-based calcium phosphate nanomedicine loaded with IR820 (mAlb-820@CaP) for high-resolution photoacoustic imaging and enhanced photothermal therapy. Biomineralization on the surface stabilizes the albumin-IR820 complex during circulation and provides calcium ions (Ca2+ ) for tissue penetration on degradation in an acidic environment. pH-triggered transcytosis of the nanomedicine enabled by caveolae-mediated endocytosis and calcium ion-induced exocytosis in 2D cellular, 3D spheroid, and in vivo tumor models is demonstrated. Notably, the extravasation and penetration ability of the nanomedicine is observed in vivo using a high-resolution photoacoustic system, and nanomedicine shows the most potent photothermal antitumor effect in vivo. Overall, the strategy provides a versatile theragnosis platform for both noninvasive photoacoustic imaging and high therapeutic efficiency resulting from deep penetration of nanomedicine.

Surfactant-Stripped Semiconducting Polymer Micelles for Tumor Theranostics and Deep Tissue Imaging in the NIR-II Window.

Photoacoustic imaging (PA) in the second near infrared (NIR-II) window presents key advantages for deep tissue imaging owing to reduced light scattering and low background signal from biological structures. Here, a thiadiazoloquinoxaline-based semiconducting polymer (SP) with strong absorption in the NIR-II region is reported. After encapsulation of SP in Pluronic F127 (F127) followed by removal of excess surfactant, a dual functional polymer system named surfactant-stripped semiconductor polymeric micelles (SSS-micelles) are generated with water solubility, storage stability, and high photothermal conversion efficiency, permitting tumor theranostics in a mouse model. SSS-micelles have a wideband absorption in the NIR-II window, allowing for the PA imaging at both 1064 and 1300 nm wavelengths. The PA signal of the SSS-micelles can be detected through 6.5 cm of chicken breast tissue in vitro. In mice or rats, SSS-micelles can be visualized in bladder and intestine overlaid 5 cm (signal to noise ratio, SNR ≈ 17 dB) and 5.8 cm (SNR over 10 dB) chicken breast tissue, respectively. This work demonstrates the SSS-micelles as a nanoplatform for deep tissue theranostics.