Development of T1/T2 dual-mode MRI contrast agents that can also treat cancer is an attractive prospect for personalized precision medicine. Unfortunately, conventional contrast agents can suffer from toxicity and lack any ability to treat cancer. An all-iron T1/T2 MR imaging agent with photothermal and drug delivery capability would overcome these issues. Here, an avocado-like Fe3+/Fe2O3 composed T1-T2 dual-mode contrast agent based on Fe-TA coordination network (CNMN) is developed. This material possesses suitable longitudinal and transverse relaxation coefficients. Moreover, the strong heat generation property of Fe-TA endows CNMN with the capability to act as a potent photothermal agent. Furthermore, CNMN can also act as an effective delivery platform for the chemotherapeutic drug doxorubicin (DOX) to achieve high effective chemo-photothermal combination therapy. The work demonstrates reliable T1-T2 MRI-guided chemo-photothermal therapy for safe and effective clinical application.

Kidney-specific delivery is critically important for the treatment of renal fibrosis with drugs such as salvianolic acid B (Sal B). Here we report a kidney-specific nanocomplex formed by the coordination-driven assembly of catechol-modified low molecular weight chitosan (HCA-Chi), calcium ions and Sal B. The prepared HCA-Chi-Ca-Sal B (HChi-Ca-Sal B) nanocomplex reversed the TGF-β1-induced epithelial-mesenchymal transition (EMT) in HK-2 cells. In vivo imaging demonstrated a kidney-specific biodistribution of the nanocomplex. The anti-fibrosis effect of HChi-Ca-Sal B was tested in a mouse model of unilateral ureteral obstruction (UUO). Significant attenuation of the morphological lesions and the levels of extracellular matrix (ECM) proteins in the tubulointerstitium was observed in mice treated with HChi-Ca-Sal B, suggesting that the nanocomplex was able to prevent fibrosis better than the treatment with free Sal B. It was concluded that the HChi-Ca-Sal B nanocomplex showed a specific renal targeting capacity and could be utilized to enhance Sal B delivery for treating renal fibrosis.

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The ability to escape endo/lysosomal trafficking is critically important to prevent entrapment of nanomedicines in lysosomes and to achieve maximum therapeutic efficacy of drugs delivered to cells through endocytosis. In this study, a novel pH-sensitive chitosan carrier with the ability to reverse its charge during endo/lysosomal trafficking is developed as a way of improving lysosomal disruption. N-Arginine-N-octyl chitosan (AOCS) is synthesized by grafting l-arginine onto carboxymethyl chitosan. The AOCS is used to modify the surface of nanostructured lipid carriers (NLC) to prepare pH-sensitive charge-reversal lysosomolytic nanocarriers (ANLC). The ANLC is loaded with 10-hydroxycamptothecin (HCPT). The results show that ANLC is able to reverse surface zeta potential from negative to positive at lysosomal pH, which contributes to improved release of encapsulated drugs into cytoplasm. The lysosomolytic capability of ANLC is confirmed by confocal microscopy and transmission electron microscopy. In vitro studies demonstrate that the anticancer activity of HCPT-loaded ANLC is improved when compared with HCPT-NLC and free HCPT. In vivo pharmacokinetics and tissue distribution analysis show improved delivery of HCPT-ANLC to subcutaneous Heps mouse liver tumors and greatly improved antitumor activity. The results present ANLC as a promising drug delivery carrier for improved antitumor therapy.