No abstract

Matrix metalloproteinases (MMPs), a class of zinc-contained endopeptidases, are closely involved in tumor growth, infiltration, metastasis, and angiogenesis. By virtue of the specifically enzymatic hydrolysis, MMPs have been widely used to turn on imaging and/or therapy function of elaborately designed enzyme-responsive nanoprobes, which is expected to realize precise diagnosis and treatment of cancer. This review systematically summarizes the classifications of MMPs, their substrates and recognized sequences, and overexpressed tumor types. The advances of MMPs-responsive nanoprobes for cancer diagnosis and therapy are focused, including trigger mechanism, design principle, and various imaging or therapy modes. Finally, this review analyzes the challenges of MMPs-responsive nanoprobes in clinical application, and provides constructive opinions for future study.

Amplifying the intracellular reactive oxygen species (ROS) level remains an urgent challenge for efficient sonodynamic therapy (SDT) of tumors. Herein, by loading ginsenoside Rk1 with manganese-doped hollow titania (MHT), a Rk1@MHT sonosensitizer was conceived to strengthen the outcome of tumor SDT. The results verify that manganese-doping remarkably elevates the UV−visible absorption and decreases the bandgap energy of titania from 3.2 to 3.0 eV, which improves ROS production under ultrasonic irradiation. Immunofluorescence and Western blot analysis demonstrate that ginsenoside Rk1 can block the critical protein of the glutathione synthesis pathway, glutaminase, thus enhancing intracellular ROS by eliminating the endogenous glutathione-depleted pathway of ROS. Manganese-doping confers the nanoprobe T 1 -weighted MRI function (r 2 /r 1 = 1.41). Moreover, the in vivo tests confirm that Rk1@MHT-based SDT eradicates liver cancer in tumor-bearing mice via dual upregulation of intracellular ROS production. In summary, our study provides a new strategy for designing high-performance sonosensitizer to achieve noninvasive cancer treatment.

Since apoptosis of foam cells can induce plaque instability, reducing intracellular lipid content while protecting foam cells from apoptosis is beneficial for the safe and efficient therapy of atherosclerosis. In this study, osteopontin-coupled polydopamine (PDA-OPN) nanoparticles were synthesized and applied to target mild photothermal therapy (PTT) of atherosclerosis. The results from laser confocal microscopy indicate that PDA-OPN nanoparticles can be specially recognized and absorbed by foam cells. Under near-infrared laser irradiation, the mild photothermal generated by PDA-OPN decreases intracellular lipid accumulation but does not induce cell apoptosis. In vivo treatments demonstrate that mild PTT can substantially reduce plaque area and improve plaque stability by upregulating the expression of plaque fibrosis in ApoE-/- mice. Our findings reinforce that the PDA-OPN nanoparticle-mediated mild PTT can inhibit atherosclerotic progression, which provides new insights for developing safe and effective treatment methods for atherosclerosis.