To integrate photothermal ablation (PTA) with radiotherapy (RT) for improved cancer therapy, we constructed a novel multifunctional core/satellite nanotheranostic (CSNT) by decorating ultrasmall CuS nanoparticles onto the surface of a silica-coated rare earth upconversion nanoparticle. These CSNTs could not only convert near-infrared light into heat for effective thermal ablation but also induce a highly localized radiation dose boost to trigger substantially enhanced radiation damage both in vitro and in vivo. With the synergistic interaction between PTA and the enhanced RT, the tumor could be eradicated without visible recurrence in 120 days. Notably, hematological analysis and histological examination unambiguously revealed their negligible toxicity to the mice within a month. Moreover, the novel CSNTs facilitate excellent upconversion luminescence/magnetic resonance/computer tomography trimodal imagings. This multifunctional nanocomposite is believed to be capable of playing a vital role in future oncotherapy by the synergistic effects between enhanced RT and PTA under the potential trimodal imaging guidance.

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Most hypoxic tumors are insensitive to radiation, which is a major obstacle in the development of conventional radiotherapy for tumor treatment. Some drugs, such as cisplatin (CDDP), have been extensively used both as an anticancer drug and clinically as a radiosensitizer to enhance radiotherapy. Herein, we develop rattle-structured multifunctional up-conversion core/porous silica shell nanotheranostics (UCSNs) for delivering CDDP to tumors for synergetic chemo-/radiotherapy by CDDP radiosensitization and magnetic/luminescent dual-mode imaging. UCSNs had a dynamic light scattering diameter of 79.1 nm and excellent water dispersity and stability. In vitro studies showed that CDDP loaded in UCSNs (UCSNs-CDDP) was more effective than free CDDP as a radiosensitizer. After injection, UCSNs-CDDP also demonstrated unambiguously enhanced radiotherapy efficacy in vivo. Our report aims at presenting a novel strategy in biomedical nanotechnology that allows simultaneous dual-mode imaging and localized therapy via synergetic chemo-/radiotherapy, which may achieve optimized therapeutic efficacy in cancer treatment.

Surgical resection, one of the main clinical treatments of intracranial glioblastoma, bears the potential risk of incomplete excision due to the inherent infiltrative character of the glioblastoma. To maximize the accuracy of surgical resection, the magnetic resonance (MR) and fluorescence imaging are widely used for the tumor preoperative diagnosis and intraoperative positioning. However, present commercial MR contrast agents and fluorescent dyes can only function for single mode of imaging and are subject to poor blood-brain barrier (BBB) permeability and nontargeting-specificity, resulting in the apparent risks of inefficient diagnosis and resection of glioblastoma. Considering the unique MR/upconversion luminescence (UCL) bimodal imaging feature of upconversion nanoparticles (UCNPs), herein, we have developed a dual-targeting nanoprobe (ANG/PEG-UCNPs) to cross the BBB, target the glioblastoma, and then function as a simultaneous MR/NIR-to-NIR UCL bimodal imaging agent, which showed a much enhanced imaging performance in comparison with the clinically used single MRI contrast (Gd-DTPA) and fluorescent dye (5-ALA). Moreover, their biocompatibility, especially to brains, was systematically assessed by the histological/hematological examination, indicating a negligible in vivo toxicity. As a proof-of-concept, the ANG/PEG-UCNPs hold the great potential in MR diagnosis and fluorescence positioning of glioblastoma for the efficient tumor surgery.

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Ultrasound (US) can activate sonosensitizers for sonodynamic therapy (SDT), but the low activation efficiency and therapeutic outcome significantly hinder its further clinical translation. Inspired by the principles of semiconductor physics and photocatalysis chemistry, we herein report on augmenting the sonocatalytic efficiency of semiconductor TiO-based nanosonosensitizers for highly efficient SDT by the integration of two-dimensional (2D) ultrathin graphene with TiO nanosonosensitizers. The high electroconductivity of graphene facilitates the separation of the electron (e) and hole (h) pairs from the energy band of TiO and avoids their recombination upon external US irradiation; thus it significantly augments the therapeutic efficiency of TiO nanosonosensitizers for SDT against tumors. By further MnO functionalization, these 2D composite nanosonosensitizers achieved tumor microenvironment-sensitive (mild acidity) T-weighted magnetic resonance imaging of tumors for therapeutic guidance and monitoring. The high photothermal-conversion capability of graphene also synergistically enhanced the SDT efficiency, achieving the complete eradication of a tumor without reoccurrence. This work provides a paradigm for augmenting semiconductor TiO-based sonocatalytic therapeutic nanomedicine by learning the physiochemical principles from traditional photocatalysis, which also demonstrates a highly efficient noninvasive and safe therapeutic modality for tumor eradication by the nanosonosensitized sonocatalytic process.

Gadolinium (Gd) doped upconversion nanoparticles (UCNPs) have been well documented as T1‐MR and fluorescent imaging agents. However, the performance of Gd3+ ions located differently in the crystal lattice still remains debatable. Here, a well‐designed model was built based on a seed‐mediated growth technique to systematically probe the longitudinal relaxivity of Gd3+ ions within the crystal lattice and at the surface of UCNPs. We found, for the first time, a nearly 100% loss of relaxivity of Gd3+ ions buried deeply within crystal lattices (> 4 nm), which we named a “negative lattice shielding effect” (n‐LSE) as compared to the “positive lattice shielding effect” (p‐LSE) for the enhanced upconversion fluorescent intensity. As‐observed n‐LSE was further found to be shell thickness dependent. By suppressing the n‐LSE as far as possible, we optimized the UCNPs' structure design and achieved the highest r1 value (6.18 mM−1s−1 per Gd3+ ion) among previously reported counterparts. The potential bimodal imaging application both in vitro and in vivo of as‐designed nano‐probes was also demonstrated. This study clears the debate over the role of bulk and surface Gd3+ ions in MRI contrast imaging and paves the way for modulation of other Gd‐doped nanostructures for highly efficient T1‐MR and upconversion fluorescent bimodal imaging.

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