Improving the effectiveness of cancer therapy will require tools that enable more specific cancer targeting and improved tumor visualization. Theranostics have the potential for improving cancer care because of their ability to serve as both diagnostics and therapeutics; however, their diagnostic potential is often limited by tissue-associated light absorption and scattering. Herein, we develop CuInSe2@ZnS:Mn quantum dots (QDs) with intrinsic multifunctionality that both enable the accurate localization of small metastases and act as potent tumor ablation agents. By leveraging the growth kinetics of a ZnS shell on a biocompatible CuInSe2 core, Mn doping, and folic acid functionalization, we produce biocompatible QDs with high near-infrared (NIR)-II fluorescence efficiency up to 31.2%, high contrast on magnetic resonance imaging (MRI), and preferential distribution in 4T1 breast cancer tumors. MRI-enabled contrast of these nanoprobes is sufficient to timely identify small metastases in the lungs, which is critically important for preventing cancer spreading and recurrence. Further, exciting tumor-resident QDs with NIR light produces both fluorescence for tumor visualization through radiative recombination pathways as well as heat and radicals through nonradiative recombination pathways that kill cancer cells and initiate an anticancer immune response, which eliminates tumor and prevents tumor regrowth in 80% of mice.

Nanovaccines have emerged as promising alternatives or complements to conventional cancer treatments. Despite the progresses, specific co‐delivery of antigen and adjuvant to their corresponding intracellular destinations for maximizing the activation of antitumor immune responses remains a challenge. Herein, a lipid‐coated iron oxide nanoparticle is delivered as nanovaccine (IONP‐C/O@LP) that can co‐deliver peptide antigen and adjuvant (CpG DNA) into cytosol and lysosomes of dendritic cells (DCs) through both membrane fusion and endosome‐mediated endocytosis. Such two‐pronged cellular uptake pattern enables IONP‐C/O@LP to synergistically activate immature DCs. Iron oxide nanoparticle also exhibits adjuvant effects by generating intracellular reactive oxygen species, which further promotes DC maturation. IONP‐C/O@LP accumulated in the DCs of draining lymph nodes effectively increases the antigen‐specific T cells in both tumor and spleen, inhibits tumor growth, and improves animal survival. Moreover, it is demonstrated that this nanovaccine is a general platform of delivering clinically relevant peptide antigens derived from human papilloma virus 16 to trigger antigen‐specific immune responses in vivo.

Various functional nanomaterials have been fabricated as diagnostic and therapeutic nanomedicines; however, the nanoparticles closely interact with proteins when immersed in biological fluids, forming a "protein corona" that critically alters the biological identity of nanomedicine. Here, we developed a robust strategy to construct theranostic nanoprobes based on protein-corona-coated Fe 3 O 4 nanoparticles and biomineralization in the corona. Water-soluble carboxylic Fe 3 O 4 nanoparticles were prepared by treating oleate-capped Fe 3 O 4 nanoparticles with Lemieux−von Rudloff reagent. Bovine serum albumin (BSA) was used as a model protein to form a corona on the surface of Fe 3 O 4 nanoparticles, endowing the Fe 3 O 4 nanoparticles with biocompatibility and nonimmunogenicity. The protein corona also provides a template for biomimetic mineralization of Fe 3+ with tannic acid (TA) to construct Fe 3 O 4 @BSA-TAFe III nanoprobes. The TA-Fe(III) biominerals can not only act as photothermal therapy agents but also interact with unsaturated transferrin in plasma to form a "hybrid" corona, enabling the nanoprobes to target tumor cells through the mediation of transferrin receptors, which commonly overexpress on tumor cell membranes. Once taken in by tumor cells, the protonation of phenol hydroxyl groups in acidic lysosomes would lead to the release of Fe 3+ , inducing tumor cell death through a ferroptosis/apoptosis hybrid pathway. In addition, the released Fe 3+ can boost the T 1 -weighted MR imaging performance, and the Fe 3 O 4 nanoparticles serve as T 2 -weighted MR imaging contrast agents. It is thus believed that the current nanoprobes can realize the enhanced dual-modality MR imaging and combined therapy of tumors through controlling the protein corona and biomineralization.

Enhanced angiography based on magnetic resonance imaging (MRI) has emerged as a noninvasive, robust, and high-resolution imaging technique for the clinical evaluation of vascular diseases. However, the effects of clinical Gd-chelating contrast agents are unsatisfactory for MRI contrast enhancement owing to their short blood half-life caused by rapid vascular extravasation, especially in microvessels. To address these issues, nanoprobes based on red blood cell membrane-coated ultrasmall NaGdF4 nanoparticles that exhibit much higher longitudinal molar relaxivity (r 1) than the clinically used contrast agent gadolinium diethylenetriaminepentaacetic acid have been developed. Furthermore, the appropriate hydrodynamic diameter and stealth nature aid the nanoprobes to reside longer within the blood vessels without extravasation, thereby increasing the contrast between the blood vessels and surrounding tissues. Through probe-enhanced three-dimensional (3D) dynamic contrast-enhanced MR angiography, the main arteries and veins of the mouse were readily discernible, and even tiny vessels with sub-millimeter diameters could be clearly depicted. With this level of outstanding MR angiography performance, the embolization and recanalization processes of the carotid artery can be serially monitored with high imaging resolution using only a single injection. Additionally, the results of clearance studies and the toxicity tests further highlight the safety features of the nanoprobe. To summarize, the nanoprobes used in this study exhibit less extravascular leakage and a longer blood half-life, thus successfully overcoming the defects of the conventional low-molecular-weight Gd-based contrast agents and demonstrating their potential usefulness in enhanced MR angiography.