A new generation of photothermal theranostic agents is developed based on PEGylated WS2 nanosheets. Bimodal in vivo CT/photoacoustic imaging reveals strong tumor contrast after either intratumoral or intravenous injection of WS2 -PEG. In vivo photothermal treatment is then conducted in a mouse tumor model, achieving excellent therapeutic efficacy with complete ablation of tumors. This work promises further exploration of transition-metal dichalcogenides for biomedical applications, such as cancer imaging and therapy.

In the original manuscript, the concentration reported in the caption of Figure 1h was incorrect. Rather than the concentration of 100 µM quoted, the concentration of H 2 O 2 used was 1 mM. The analysis and conclusions of the article are not affected. The caption should thus read: "h) Oxygen generation in H 2 O 2 solutions (1 × 10 −3 M) with HMCP added under different pH values (7.4 and 6.5). The decrease of oxygen concentration in the system for the sample under pH 7.4 (after ≈150 s) was due to rapid consumption of H 2 O 2 .

Photodynamic therapy (PDT) is considered as a safe and selective way to treat a wide range of cancers as well as nononcological disorders. However, as oxygen is required in the process of PDT, the hypoxic tumor microenvironment has largely limited the efficacy of PDT to treat tumors especially those with relatively large sizes. To this end, we uncover that hyaluronidase (HAase), which breaks down hyaluronan, a major component of extracellular matrix (ECM) in tumors, would be able to enhance the efficacy of nanoparticle-based PDT for in vivo cancer treatment. It is found that the administration of HAase would lead to the increase of tumor vessel densities and effective vascular areas, resulting in increased perfusion inside the tumor. As a result, the tumor uptake of nanomicelles covalently linked with chlorine e6 (NM-Ce6) would be increased by ∼2 folds due to the improved "enhanced permeability and retention" (EPR) effect, while the tumor oxygenation level also shows a remarkable increase, effectively relieving the hypoxia state inside the tumor. Those effects taken together offer significant benefits in greatly improving the efficacy of PDT delivered by nanoparticles. Taking advantage of the effective migration of HAase from the primary tumor to its drainage sentinel lymph nodes (SLNs), we further demonstrate that this strategy would be helpful to the treatment of metastatic lymph nodes by nanoparticle-based PDT. Lastly, both enhanced EPR effect of NM-Ce6 and relieved hypoxia state of tumor are also observed after systemic injection of modified HAase, proving its potential for clinical translation. Therefore, our work presents a new concept to improve the efficacy of nanomedicine by modulating the tumor microenvironment.

Nanoscale metal-organic particles (NMOPs) are constructed from metal ions and organic bridging ligands via the self-assembly process. Herein, we fabricate NMOPs composed of Mn(2+) and a near-infrared (NIR) dye, IR825, obtaining Mn-IR825 NMOPs, which are then coated with a shell of polydopamine (PDA) and further functionalized with polyethylene glycol (PEG). While Mn(2+) in such Mn-IR825@PDA-PEG NMOPs offers strong contrast in T1-weighted magnetic resonance (MR) imaging, IR825 with strong NIR optical absorbance shows efficient photothermal conversion with great photostability in the NMOP structure. Upon intravenous injection, Mn-IR825@PDA-PEG shows efficient tumor homing together with rapid renal excretion behaviors, as revealed by MR imaging and confirmed by biodistribution measurement. Notably, when irradiated with an 808 nm laser, tumors on mice with Mn-IR825@PDA-PEG injection are completely eliminated without recurrence within 60 days, demonstrating the high efficacy of photothermal therapy with this agent. This study demonstrates the use of NMOPs as a potential photothermal agent, which features excellent tumor-targeted imaging and therapeutic functions, together with rapid renal excretion behavior, the latter of which would be particularly important for future clinical translation of nanomedicine.

The development of cancer combination therapies, many of which rely on nanoscale theranostic agents, has received increasing attention in recent years. In this work, polyethylene glycol (PEG) modifi ed mesoporous silica (MS) coated single-walled carbon nanotubes (SWNTs) are fabricated and utilized as a multifunctional platform for imaging guided combination therapy of cancer. A model chemotherapy drug, doxorubicin (DOX), could be loaded into the mesoporous structure of the obtained SWNT@MS-PEG nano-carriers with high effi ciency. Upon stimulation under near-infrared (NIR) light, photothermally triggered drug release from DOX loaded SWNT@MS-PEG is observed inside cells, resulting in a synergistic cancer cell killing effect. As revealed by both photoacoustic (PA) and magnetic resonance (MR) imaging, we further uncover effi cient tumor accumulation of SWNT@MS-PEG/DOX after intravenous injection into mice. In vivo combination therapy using this agent is further demonstrated in a mouse tumor model, achieving a remarkable synergistic anti-tumor effect superior to that obtained by mono-therapy. Our work presents a new type of theranostic nano-platform, which could load therapeutic molecules with high effi ciency, be responsive to external NIR stimulation, and at the same time serve as a diagnostic imaging agent.